Trial Outcomes & Findings for A Phase III Study of Apixaban in Patients With Atrial Fibrillation (NCT NCT00496769)

NCT ID: NCT00496769

Last Updated: 2018-06-15

Results Overview

Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 6421 participants
• Primary outcome timeframe: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)
• Results posted on: 2018-06-15

Participant Flow

A total 6421 patients were enrolled in the study. Of these, 5598 were randomized (2807 to apixaban and 2791 to acetylsalicylic acid). Most (435) of the patients who were not randomized (823) no longer met study criteria. Of those randomized, 5578 received treatment (2798 with apixaban, and 2780 with acetylsalicylic acid).

Participant milestones

Measure	Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.	Open Label Apixaban Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
Double Blind STARTED	2807	2791	0
Double Blind Received Treatment	2798	2708	0
Double Blind COMPLETED	2249	2142	0
Double Blind NOT COMPLETED	558	649	0
Open Label STARTED	0	0	3275
Open Label COMPLETED	0	0	2264
Open Label NOT COMPLETED	0	0	1011

Reasons for withdrawal

Measure	Apixaban, 2.5 or 5 mg Twice Daily Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.	Open Label Apixaban Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
Double Blind >=1 reason assigned per patient	558	649	0
Open Label >=1 reason assigned per patient	0	0	1011

Baseline Characteristics

A Phase III Study of Apixaban in Patients With Atrial Fibrillation

Baseline characteristics by cohort

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2807 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2791 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion	Total n=5598 Participants Total of all reporting groups
Age, Continuous	69.7 years STANDARD_DEVIATION 9.44 • n=5 Participants	70.0 years STANDARD_DEVIATION 9.71 • n=7 Participants	69.9 years STANDARD_DEVIATION 9.58 • n=5 Participants
Age, Customized < 65 years	855 Participants n=5 Participants	865 Participants n=7 Participants	1720 Participants n=5 Participants
Age, Customized >=65 but <75 years	1049 Participants n=5 Participants	938 Participants n=7 Participants	1987 Participants n=5 Participants
Age, Customized >=75 years	903 Participants n=5 Participants	988 Participants n=7 Participants	1891 Participants n=5 Participants
Sex: Female, Male Female	1147 Participants n=5 Participants	1174 Participants n=7 Participants	2321 Participants n=5 Participants
Sex: Female, Male Male	1660 Participants n=5 Participants	1617 Participants n=7 Participants	3277 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Asian	541 Participants n=5 Participants	544 Participants n=7 Participants	1085 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	10 Participants n=5 Participants	26 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized White	2221 Participants n=5 Participants	2178 Participants n=7 Participants	4399 Participants n=5 Participants
Race/Ethnicity, Customized Other	26 Participants n=5 Participants	36 Participants n=7 Participants	62 Participants n=5 Participants
Number of Participants by Number of Risk Factors for Stroke 1 or fewer	1085 Participants n=5 Participants	1077 Participants n=7 Participants	2162 Participants n=5 Participants
Number of Participants by Number of Risk Factors for Stroke 2 or more	1722 Participants n=5 Participants	1714 Participants n=7 Participants	3436 Participants n=5 Participants
Number of Participants With Risk Factors for Stroke Age of 75 years or older	903 Participants n=5 Participants	988 Participants n=7 Participants	1891 Participants n=5 Participants
Number of Participants With Risk Factors for Stroke Prior stroke or transient ischemic attack	390 Participants n=5 Participants	374 Participants n=7 Participants	764 Participants n=5 Participants
Number of Participants With Risk Factors for Stroke Heart failure (NYHA class ≥2) or LVEF ≤35%	961 Participants n=5 Participants	926 Participants n=7 Participants	1887 Participants n=5 Participants
Number of Participants With Risk Factors for Stroke Diabetes mellitus	536 Participants n=5 Participants	559 Participants n=7 Participants	1095 Participants n=5 Participants
Number of Participants With Risk Factors for Stroke Hypertension requiring pharmacologic treatment	2408 Participants n=5 Participants	2429 Participants n=7 Participants	4837 Participants n=5 Participants
Number of Participants With Risk Factors for Stroke Peripheral artery disease	66 Participants n=5 Participants	78 Participants n=7 Participants	144 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)

Population: Participants who received at least 1 dose of study drug.

Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.)

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2807 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2791 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period	1.62 Percentage of events	3.63 Percentage of events

SECONDARY outcome

Timeframe: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)

Population: Participants who received at least 1 dose of study drug.

Event rate=percent of participants with an event divided by the total participants in the arm.

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2807 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2791 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period	4.21 Percentage of events per year	6.35 Percentage of events per year

SECONDARY outcome

Timeframe: Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)

Population: Participants who received at least 1 dose of study drug.

Event rate=percent of participants with an event divided by the total participants in the arm.

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2807 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2791 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death All-cause death (n=111, 140)	3.51 Percentage of events per year	4.42 Percentage of events per year
Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death Net clinical benefit (n=163, 220)	5.23 Percentage of events per year	7.13 Percentage of events per year
Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death Vascular death (n=84, 96)	2.65 Percentage of events per year	3.03 Percentage of events per year

SECONDARY outcome

Timeframe: First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010

Population: Participants who received at least 1 dose of study drug.

Event rate=percent of participants with an event divided by the total participants in the arm.

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period Major bleeding	1.41 Percentage of events per year	0.92 Percentage of events per year
Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period Major or CRNM bleeding	4.46 Percentage of events per year	3.24 Percentage of events per year
Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period All bleeding	10.85 Percentage of events per year	8.32 Percentage of events per year

SECONDARY outcome

Timeframe: Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy)

Population: Participants who received at least 1 dose of study drug.

Event rate=percent of participants with an event divided by the total participants in the arm.

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period	10.85 Percentage of events per year	8.32 Percentage of events per year

SECONDARY outcome

Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Population: Participants who received at least 1 dose of study drug.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome AEs	1833 Participants	1925 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome SAEs	657 Participants	804 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome Bleeding AEs	281 Participants	259 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome Discontinuations due to AE	266 Participants	362 Participants
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome Deaths	91 Participants	115 Participants

SECONDARY outcome

Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Population: Participants who received at least 1 dose of study drug. n=number evaluable

BL=baseline, LLN=lower limit of normal, ULN=upper limit of normal. Hemoglobin (g/dL), low: BL>2 or value ≤8; hematocrit(%), low: <0.75*BL; erythrocytes (*10^6 cells/μL), low: <0.75*BL; platelet count (*10^9 cells/L),low: <100*10^9 cells/L; leukocytes (*10^3 cells/μL), low if <0.8*BL and BL<LLN or <LLN and BL >ULN or <0.75*LLN when BL is missing or LLN ≤BL≤ ULN, high if >1.2*BL and BL>ULN or >ULN when BL and BL<LLN or >1.25*ULN when BL is missing or LLN≤BL≤ULN; neutrophils (absolute), low: <1.0*10^3 cells/μL; eosinophils (absolute), high: >0.750*10^3 cells/μL; basophils (absolute), high: >0.4*10^3 cells/μL; monocytes (absolute), high: 2*10^3 cells/μL; lymphocytes (absolute), low if <0.75*10^3 cells/μL, high if >7.50*10^3 cells/μL; ALP (U/L), high: 2*ULN; AST (U/L), high: 3*ULN; AST (U/L), high: 3*ULN; bilirubin, total (mg/dL), high: >2*ULN; bilirubin, direct (mg/dL), high: 1.5*ULN; BUN (mg/dL), high:>2*ULN; creatinine (mg/dL), high: >1.5*ULN.

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Hematocrit, high (n=1728, 1687)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Erythrocytes, high (n=1728, 1687)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Leukocytes, low (n=1738, 1698)	12 Participants	14 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Neutrophils (absolute), low (n=2170, 2138)	2 Participants	1 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Eosinophils (absolute), high (n=2170, 2138)	48 Participants	68 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Basophils (absolute), low (n=2170, 2138)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Basophils (absolute), high (n=2170, 2138)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Monocytes (absolute), low (n=2170, 2138)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Monocytes (absolute), high (n=2170, 2138)	0 Participants	2 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Lymphocytes (absolute), low (n=2170, 2138)	52 Participants	62 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Lymphocytes (absolute), high (n=2170, 2138)	4 Participants	5 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Alkaline phosphatase (ALP), low (n=2781, 2758)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality ALP, high (n=2781, 2758)	34 Participants	27 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Aspartate phosphatase (AST), low (n=2779, 2753)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality AST, high (n=2779, 2753)	28 Participants	33 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Alanine aminotransferase (ALT), low (n=2779, 2753)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality ALT, high (n=2779, 2753)	23 Participants	31 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Bilirubin (total), low (n=2781, 2758)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Bilirubin (total), high (n=2781, 2758)	30 Participants	43 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Bilirubin (direct), low (n=2773, 2750)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Bilirubin (direct), high (n=2773, 2750)	241 Participants	248 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Blood urea nitrogen (BUN), low (n=2201, 2172)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality BUN, high (n=2201, 2172)	42 Participants	50 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Creatinine, low (n=2209, 2178)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Creatinine, high (n=2209, 2178)	67 Participants	71 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Platelet count, low (n=2148, 2098)	7 Participants	10 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Platelet count, high (n=2148, 2098)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Leukocytes, high (n=1738, 1698)	14 Participants	18 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Hemoglobin, low (n=1956, 1893)	131 Participants	120 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Hemoglobin, high (n=1956, 1893)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Hematocrit, low (n=1728, 1687)	13 Participants	9 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Erythrocytes, low (n=1728, 1687)	12 Participants	12 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Neutrophils (absolute), high (n=2170, 2138)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality Eosinophils (absolute), low (n=2170, 2138)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Population: Participants who received at least 1 dose of study drug. n=number evaluable

LLN=lower limit of normal; ULN=upper limit of normal; BL=baseline. Sodium, serum (mEq/L):low if <0.95*BL and BL<LLN or <LLN and BL>ULN or <0.95*LLN when BL missing or LLN ≤BL≤ULN, high if >1.05*BL and BL>ULN or >ULN and BL<LLN or >1.05*ULN when BL missing or LLN≤BL≤ULN; potassium(mEq/L):low if <0.90*BL and BL<LLN or <LLN and BL>ULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL and BL>ULN or>ULN and BL<LLN or >1.10*ULN when BL missing or LLN≤BL≤ULN; chloride(mEq/L):low if <0.90*BL and BL<LLN or <LLN and BL>ULN or <0.90*LLN if BL missing or LLN≤BL ≤ULN, high if >1.10*BL and BL>ULN or >ULN and BL<LLN or >1.10* ULN if BL missing or LLN≤BL≤ULN; calcium(mg/dL):low if <0.75*BL and BL<LLN or <LLN and BL>ULN or <0.80*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL and BL>ULN or >ULN if BL<LLN or >1.20*ULN if BL missing or LLN≤BL≤ULN ; bicarbonate(mEq/L):low if <0.75*BL when BL<LLN or <LLN when BL>ULN or <0.75*LLN if BL missing or LLN≤BL≤ULN, high if >1.25*BL when BL>ULN or >ULN

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Sodium (serum), low (n=1768, 1740)	2 Participants	6 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Sodium (serum), high (n=1768, 1740)	1 Participants	2 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Potassium (serum), low (n=1763, 1737)	6 Participants	8 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Potassium (serum), high (n=1763, 1737)	20 Participants	28 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Chloride (serum), low (n=1768, 1740)	0 Participants	3 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Chloride (serum), high (n=1768, 1740)	0 Participants	1 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Calcium (total), low (n=106, 109)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Calcium (total), high (n=106, 109)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Bicarbonate, low (n=1664, 1619)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Bicarbonate, high (n=1664, 1619)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: First dose of study drug (Day 1) to 30 days after last dose of blinded study drug

Population: Participants who received at least 1 dose of study drug. n=number evaluable

ULN=upper limit of normal; LLN=lower limit of normal; BL=baseline. Creatine kinase (U/L), high:>5*ULN; protein, total(g/L):low if <0.90*BL when BL<LLN or <LLN when B >ULN or <0.90*LLN when BL is missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN when BL<LLN or >1.10*ULN if BL missing or LLN≤BL≤ULN.Protein,total(g/L): low if <0.90*BL if BL<LLN or <LLN if BL>ULN or <0.90*LLN if BL missing or LLN≤BL≤ULN, high if >1.10*BL if BL>ULN or >ULN if BL<LLN or >1.10*ULN if BL or LLN≤BL≤ULN; glucose, serum fasting (mg/dL): low if <0.8*BL if BL<LLN or <LLN when BL>ULN or <0.8*LLN when BL missing or LLN≤BL≤ULN, high if >2*BL when BL>ULN or >ULN when BL<LLN or >1.5*ULN if BL missing or LLN≤BL≤ULN; uric acid (mg/dL), high: >2*BL and BL>ULN or>1.5*ULN when BL missing or BL≤ULN; glucose, urine, high; protein, urine, high; blood, urine, high; leukocyte esterase, urine, high; RBC count, urine (Hpf), high; WBC count, urine (Hpf), high: ≥2 if BL=missing,=0 or =0.5 or if ≥3 if BL=1, or if ≥4 and BL≥2.

Outcome measures

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 Participants Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 Participants Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Creatine kinase, low (n=2780, 2758)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Creatine kinase, high (n=2780, 2758)	13 Participants	25 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Protein (total), low (n=103, 109)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Uric acid, low (n=386, 390)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Glucose (urine), low (n=2, 3)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Glucose (urine), high (n=2, 3)	0 Participants	1 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Protein (urine), high (n=3, 5)	1 Participants	1 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Blood (urine), high (n=3, 5)	1 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Red blood cells (RBC) (urine), low (n=2,2)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) White blood cells (urine), low (n=2,2)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Protein (total), high (n=103, 109)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Uric acid, high (n=386, 390)	1 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Protein (urine), low (n=3, 5)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Blood (urine), low (n=3, 5)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Leukocyte esterase (urine), low (n=3,5)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) Leukocyte esterase (urine), high (n=3,5)	0 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) RBC (urine), high (n=2,2)	1 Participants	0 Participants
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) WBC (urine), high (n=2,2)	0 Participants	0 Participants

Adverse Events

Apixaban, 2.5 or 5 mg Twice Daily

Serious events: 657 serious events

Other events: 207 other events

Deaths: 111 deaths

Acetylsalicylic Acid, 81-324 mg Once Daily

Serious events: 804 serious events

Other events: 267 other events

Deaths: 140 deaths

Open Label Apixaban

Serious events: 1228 serious events

Other events: 180 other events

Deaths: 286 deaths

Serious adverse events

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 participants at risk Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 participants at risk Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.	Open Label Apixaban n=3275 participants at risk Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
Gastrointestinal disorders Intestinal haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Microvascular angina	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Social circumstances Cardiac assistance device user	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Congenital, familial and genetic disorders Atrial septal defect	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Atrioventricular block	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Bile duct stone	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Blood blister	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Eyelid ptosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Blood magnesium decreased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Bradycardia	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.34% 11/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm benign	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Bronchopneumonia	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cardiac pacemaker removal	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cardiac pacemaker replacement	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Cerebral haemorrhage traumatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Keratitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cholecystectomy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Colitis	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Conduction disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Confusional state	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Deep vein thrombosis	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Device pacing issue	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Drug toxicity	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Duodenal ulcer	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Dysuria	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Foot fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastric disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastritis	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastritis erosive	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Gout	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Haematemesis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Helicobacter gastritis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Hepatic amoebiasis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Endocrine disorders Hyperthyroidism	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Implant site effusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Implantable defibrillator insertion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Influenza	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Intestinal obstruction	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Joint dislocation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Left ventricular dysfunction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Limb traumatic amputation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Lumbar hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Malnutrition	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Meningitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Migraine	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Mitral valve prolapse	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Mouth haemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Muscle strain	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Myopathy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Omentum neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Tolosa-hunt syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Parkinson's disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Peptic ulcer	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Prostatic obstruction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Prostatic operation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal failure	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Retinal artery occlusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Retroperitoneal haematoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Skin infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Tarsal tunnel decompression	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Thrombophlebitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Tracheitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Urinary retention	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Ventricular failure	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Vestibular neuronitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Abscess	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Abscess limb	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Social circumstances Activities of daily living impaired	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Allergic bronchitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Amoebic dysentery	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Anaemia	0.43% 12/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 11/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.70% 23/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Atrial fibrillation	2.6% 72/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	2.5% 70/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	3.5% 113/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Bipolar disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal distension	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardio-respiratory arrest	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiovascular insufficiency	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebral haemorrhage	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.31% 10/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Cholestasis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.43% 12/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.32% 9/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.73% 24/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Colonic polyp	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Coronary artery bypass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cubital tunnel syndrome	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Decreased appetite	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Depressed level of consciousness	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Device lead damage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Dyspepsia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Dysphagia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.46% 13/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 11/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.67% 22/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Embolic stroke	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Fall	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.37% 12/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Femoral artery embolism	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Generalised oedema	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gingival bleeding	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Haemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Hemiparesis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Hernia pain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Hysterectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Implantable defibrillator replacement	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Inguinal hernia repair	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Jaw fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Lung infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Lymphocele	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Mesenteric artery embolism	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to abdominal cavity	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Muscle rupture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Myocardial ischaemia	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Oesophageal achalasia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal mass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Partial seizures	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Peripheral artery angioplasty	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Peripheral embolism	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Social circumstances Physical assault	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Post procedural diarrhoea	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Presyncope	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Procedural pain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Psoas abscess	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Rectal haemorrhage	0.25% 7/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.24% 8/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Reflux oesophagitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal impairment	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal infarct	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.32% 9/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Retinal detachment	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Road traffic accident	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Sciatica	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Sinoatrial block	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Skin lesion	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Staphylococcal sepsis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Starvation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Subileus	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Sudden cardiac death	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Supraventricular tachycardia	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Tachyarrhythmia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Therapeutic embolisation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Transfusion	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders VIIth nerve paralysis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Venous insufficiency	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Vertebroplasty	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Viral infection	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Acute coronary syndrome	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Aortic rupture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Arrhythmia supraventricular	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Arterial thrombosis limb	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Arthritis bacterial	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Asthenia	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.27% 9/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Atrial tachycardia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Bladder mass	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Cachexia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cardiac ablation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Cardiac death	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cardiac pacemaker insertion	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.27% 9/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiopulmonary failure	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Carditis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebral microhaemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebral thrombosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cervical root pain	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Coronary artery disease	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.49% 16/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Coronary artery insufficiency	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Cystoscopy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Dehydration	0.25% 7/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.34% 11/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Ear and labyrinth disorders Ear disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Ejection fraction decreased	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Encephalopathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Endocarditis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Epilepsy	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Escherichia bacteraemia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Femoral artery occlusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastric ulcer haemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Gastroenteritis	0.29% 8/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.43% 14/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastrointestinal haemorrhage	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.32% 9/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.61% 20/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastrointestinal hypomotility	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders General physical health deterioration	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Haematuria	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 13/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Head injury	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Hepatic enzyme increased	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Hepatitis	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Hypertension	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.32% 9/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 13/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Ileus	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Intracardiac thrombus	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Joint swelling	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Klebsiella bacteraemia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Lower limb fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Lower respiratory tract infection	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Lumbar radiculopathy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Lymphadenopathy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal wall haematoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Medical device complication	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Meniscus lesion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Neuropathy peripheral	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Oesophagitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Orchidectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Orthostatic hypotension	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.39% 11/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.52% 17/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Osteomyelitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Pancreatitis acute	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Paraesthesia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Percutaneous coronary intervention	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pneumonia	1.3% 37/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	2.0% 55/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	3.0% 99/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pneumonia klebsiella	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pneumonia pneumococcal	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Polyarthritis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Proctitis ulcerative	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Pubis fracture	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pyelonephritis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pyometra	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal failure chronic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Sick sinus syndrome	0.29% 8/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 11/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Skin neoplasm excision	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Spinal column injury	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Spinal fusion surgery	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Therapeutic agent toxicity	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Thrombocytopenia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Thrombosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Toe amputation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Tooth extraction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Transurethral prostatectomy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Urethral disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Venous thrombosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Ventricular tachycardia	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Ear and labyrinth disorders Vertigo	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Angina unstable	0.71% 20/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.43% 12/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.52% 17/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Angiogram	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Aplastic anaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Atrioventricular block complete	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiac failure congestive	1.4% 39/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	1.0% 28/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	1.6% 53/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cardiac pacemaker battery replacement	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiomyopathy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Cellulitis	0.21% 6/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 13/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebral haematoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Cholecystitis chronic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Convulsion	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Coronary angioplasty	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Decubitus ulcer	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Delirium	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Rheumatic heart disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Dermatitis herpetiformis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Sinus arrest	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Duodenitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Femur fracture	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.34% 11/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastric haemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Headache	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Hepatic failure	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Hiccups	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Hip arthroplasty	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.24% 8/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Hip surgery	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hyponatraemia	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Ischaemic cardiomyopathy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Ischaemic stroke	0.68% 19/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	1.7% 46/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.67% 22/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Lacunar infarction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma metastatic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Lung disorder	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymph node cancer metastatic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Melaena	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Menometrorrhagia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Muscle spasms	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Obesity	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Oedema peripheral	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Oesophageal varices haemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Patella fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Post procedural fistula	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Psychotic disorder	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 11/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer metastatic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Rib fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sebaceous carcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Sinus polyp	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Spigelian hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Systemic inflammatory response syndrome	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Tachycardia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Transient ischaemic attack	0.36% 10/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	1.0% 29/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.40% 13/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Tricuspid valve incompetence	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Uterine dilation and curettage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Vascular encephalopathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Ventricular arrhythmia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Ventricular fibrillation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal adhesions	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Adverse drug reaction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Amaurosis fugax	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Angioplasty	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Aortic dissection	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Arrhythmia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Arterial stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Arteriogram coronary	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Benign prostatic hyperplasia	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.24% 8/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma stage 0	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Chest discomfort	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Cholelithiasis	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Clostridium colitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Coagulopathy	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Constipation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Cough	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Device malfunction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Diabetic hyperglycaemic coma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Diverticulitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Electrolyte imbalance	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Eye operation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Food poisoning	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Gangrene	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastric ulcer	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastrointestinal perforation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Haemorrhagic diathesis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Haemorrhagic stroke	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.24% 8/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Heart valve operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Hospitalisation	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hyperglycaemia	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hypovolaemia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Incisional hernia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Iron deficiency anaemia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Localised infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma stage I	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Mastectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Mesenteric artery thrombosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Nausea	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Nodal arrhythmia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Pain in extremity	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Pelvic mass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pelvic neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Seizure	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pneumonia viral	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer stage III	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Ascites	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal colic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Respiratory tract infection	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Retinal artery embolism	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Barrett's oesophagus	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Chronic gastritis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Salivary gland operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Sepsis	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.52% 17/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Shock	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Sinus arrhythmia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Sinus bradycardia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Sinusitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Colitis ulcerative	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Thrombophlebitis superficial	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Endocrine disorders Thyroid haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Traumatic haematoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Urinary tract infection	0.39% 11/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.54% 15/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.73% 24/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Vaginal haemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Wound secretion	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal pain	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Angina pectoris	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.32% 9/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.43% 14/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Animal bite	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Ankle fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Aortic aneurysm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Aortic stenosis	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Aphasia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Arteriosclerosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Asthma	0.21% 6/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Back pain	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.27% 9/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.37% 12/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basosquamous carcinoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Bile duct stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Bradyarrhythmia	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Brain stem infarction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Bronchiectasis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Calculus urinary	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiac arrest	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.25% 7/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.31% 10/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiac failure chronic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Carotid arterial embolus	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Cataract	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebral cyst	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebrovascular disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Cervical vertebral fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Clostridium difficile colitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cor pulmonale	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Depression	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Diarrhoea	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.34% 11/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Faecaloma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Fatigue	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Femoral neck fracture	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.24% 8/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Gastroenteritis salmonella	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Gouty arthritis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Haemarthrosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Haematoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Heart rate irregular	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Herpes zoster	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Humerus fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications In-stent arterial restenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Diverticulum intestinal	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications In-stent coronary artery restenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Inguinal hernia	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.37% 12/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Ischaemic cerebral infarction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Liposarcoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Mitral valve incompetence	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Mitral valve repair	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Multi-organ failure	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Myocardial infarction	0.39% 11/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.43% 12/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.73% 24/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Oedema	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Oesophageal stenosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Pallor	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Pancreatitis	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer recurrent	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Purpura	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pyelonephritis acute	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Pyrexia	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Radius fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Red blood cell sedimentation rate increased	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Renal stone removal	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Small intestinal obstruction	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Syncope	0.29% 8/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.65% 18/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.79% 26/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Thromboembolectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Upper respiratory tract infection	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Urosepsis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Varicose vein	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal strangulated hernia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Acute abdomen	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Altered state of consciousness	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Angioedema	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Aortic valve incompetence	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Appendicectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Appendicitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Brain stem haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Bursal operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiac failure acute	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.25% 7/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cardioversion	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebellar ataxia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebrovascular accident	0.57% 16/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	1.4% 40/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.46% 15/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Cholangitis	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Cholecystitis acute	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon neoplasm	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Congenital, familial and genetic disorders Congenital cystic kidney disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Contusion	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Coronary artery occlusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Death	0.50% 14/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.32% 9/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	1.2% 38/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Diabetes mellitus	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Facial bones fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastritis haemorrhagic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Helicobacter infection	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Hernia repair	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Hiatus hernia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Hip fracture	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.37% 12/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Hypotension	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.14% 4/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Endocrine disorders Hypothyroidism	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Incisional hernia repair	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Injury	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Left ventricular failure	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Leukocytosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Liver disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Liver function test abnormal	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Multiple injuries	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Non-cardiac chest pain	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Oral candidiasis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Overdose	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Peripheral ischaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Phlebitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.25% 7/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.36% 10/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.37% 12/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Prostatic specific antigen increased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Rectal polypectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Right ventricular failure	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Splenic artery aneurysm	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Subdural haematoma	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Sudden death	0.32% 9/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.43% 12/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.98% 32/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Swelling	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Tooth loss	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Urinary tract infection bacterial	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Ear and labyrinth disorders Vertigo positional	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Vomiting	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Weight decreased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the cervix	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebrovascular insufficiency	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cognitive disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Dementia alzheimer's type	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Diabetic neuropathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Dysarthria	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Dyskinesia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Haemorrhage intracranial	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Hydrocephalus	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Hypoaesthesia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Hypoglycaemic coma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Hyponatraemic encephalopathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Intraventricular haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Myoclonus	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Neuritis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Neuroglycopenia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Paraplegia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Simple partial seizures	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Status epilepticus	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Subdural effusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Thrombotic stroke	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Uraemic encephalopathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Vascular dementia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Pregnancy, puerperium and perinatal conditions Cephalhaematoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Product Issues Lead dislodgement	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Adjustment disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Bipolar i disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Completed suicide	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Hallucination	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Insomnia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Mental disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Stress	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Suicidal ideation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Suicide attempt	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Acute kidney injury	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.73% 24/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Azotaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Calculus bladder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Calculus urethral	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Chronic kidney disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Cystitis haemorrhagic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Diabetic nephropathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Haemorrhage urinary tract	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Nephrolithiasis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Postrenal failure	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal tubular necrosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Breast mass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Metrorrhagia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Postmenopausal haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Prostatic hypoplasia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Prostatomegaly	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Spermatic cord disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Reproductive system and breast disorders Uterine polyp	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Asphyxia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Pulmonary vascular disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Aortic aneurysm repair	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Aortic valve replacement	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Benign tumour excision	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Bladder polypectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cancer surgery	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Carotid endarterectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Choledochoenterostomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Coronary arterial stent insertion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Endarterectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Endovenous ablation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Gastric bypass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Gastrointestinal tube insertion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Heart valve replacement	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures High frequency ablation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Hydronephrosis repair	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Knee operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Laparotomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Liver operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Lung operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Medical device implantation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Medical device removal	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Mitral valve replacement	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Pancreaticoduodenectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Plastic surgery to the face	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Proctocolectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Rehabilitation therapy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Skin lesion removal	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Thyroid operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Thyroidectomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Tracheostomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Ureteral stent insertion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Urethral stent insertion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Vascular graft	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Ventriculo-peritoneal shunt	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Weight loss diet	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Wrist surgery	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Unassigned	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.21% 7/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Accelerated hypertension	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Aneurysm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Arterial disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Arterial occlusive disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Circulatory collapse	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Hypertensive emergency	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Hypovolaemic shock	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Leriche syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Pelvic venous thrombosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Peripheral artery stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Peripheral vascular disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Peripheral venous disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Subclavian artery stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Temporal arteritis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Varicose ulceration	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Varicose vein ruptured	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Venous haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Anaemia megaloblastic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Leukopenia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Blood and lymphatic system disorders Pancytopenia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Acute left ventricular failure	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Aortic valve stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiac asthma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiac disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Congestive cardiomyopathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Defect conduction intraventricular	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Hypertensive heart disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Mitral valve disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Mitral valve stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Nodal rhythm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Pericarditis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Pericarditis constrictive	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Prinzmetal angina	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Sinus node dysfunction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.55% 18/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Ventricular extrasystoles	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Congenital, familial and genetic disorders Liddle's syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Ear and labyrinth disorders Ear haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal pain upper	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Abdominal wall abscess	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Acute myocardial infarction	0.39% 11/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.68% 19/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.76% 25/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Alcohol abuse	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Anxiety	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Atrial flutter	0.25% 7/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.24% 8/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.32% 9/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.31% 10/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Bronchitis	0.25% 7/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.25% 7/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.46% 15/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Calculus ureteric	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiac failure	2.1% 60/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	2.7% 76/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	3.5% 116/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Cardiogenic shock	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Cataract operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebral infarction	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.31% 10/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Chest pain	0.57% 16/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.86% 24/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.85% 28/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Cholecystitis	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholesteatoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Chronic sinusitis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Endocrine disorders Goitre	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Concussion	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Dementia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Dengue fever	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Diverticulum	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Dizziness	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.36% 10/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Emphysema	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.18% 5/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.22% 6/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.49% 16/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Eye haemorrhage	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Fasciotomy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Gait disturbance	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Gallbladder operation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Gastroduodenitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Genitourinary operation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Haematochezia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Haemorrhagic cerebral infarction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Haemorrhoid operation	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Hand fracture	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Hepatitis C	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Endocrine disorders Hyperparathyroidism	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Hypertensive crisis	0.21% 6/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Hypertensive nephropathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hypoglycaemia	0.29% 8/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.11% 3/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.37% 12/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Intermittent claudication	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Knee arthroplasty	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Lethargy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Endocrine disorders Thyroid mass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lip and/or oral cavity cancer	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Lobar pneumonia	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Loss of consciousness	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.11% 3/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 5/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.46% 15/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Malaise	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Respiratory, thoracic and mediastinal disorders Mediastinal mass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Metabolic encephalopathy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Multiple fractures	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm prostate	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma stage III	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Osteochondrosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Pain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Palpitations	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.18% 6/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Pancreatitis chronic	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Psychiatric disorders Panic attack	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Papilloma excision	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Cardiac disorders Pericardial effusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Peripheral nerve palsy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Postoperative wound infection	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Eye pain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Renal failure acute	0.29% 8/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.32% 9/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Septic shock	0.14% 4/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.37% 12/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Skin graft	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Skull fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Traumatic brain injury	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Tremor	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Renal and urinary disorders Urinary incontinence	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.07% 2/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Vertebrobasilar insufficiency	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Eye disorders Vitreous haemorrhage	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Wound infection	0.07% 2/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Abdominal hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Surgical and medical procedures Abdominoplasty	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Vascular disorders Arteriosclerosis obliterans	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.04% 1/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Tendon pain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Haemorrhoids	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Ileus paralytic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Incarcerated umbilical hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Large intestine perforation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Large intestine polyp	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Mallory-weiss syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Oesophageal dilatation	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Proctitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Umbilical hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.43% 14/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Gastrointestinal disorders Volvulus	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Exercise tolerance decreased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Incarcerated hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Multiple organ dysfunction syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Peripheral swelling	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
General disorders Unevaluable event	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Acute hepatic failure	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Cholangitis acute	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Hepatic cyst	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Hepatitis fulminant	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Hepatomegaly	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Hepatobiliary disorders Portal hypertension	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Immune system disorders Anaphylactic reaction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Abdominal wall infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Colonic abscess	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Cystitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Diabetic foot infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Disseminated tuberculosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Diverticulitis intestinal haemorrhagic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Empyema	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Encephalitis viral	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Endophthalmitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Erysipelas	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.24% 8/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Escherichia infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Gastroenteritis viral	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Gastrointestinal infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Groin infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Hepatitis E	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Infectious pleural effusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Listeriosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Liver abscess	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Nasopharyngitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Nosocomial infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Oesophageal candidiasis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Ophthalmic herpes zoster	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Orchitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Periorbital cellulitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Peritonitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pneumonia escherichia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pneumonia influenzal	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Prostate infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Pulmonary tuberculosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Sepsis syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Staphylococcal infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Tracheobronchitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Tuberculosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Tuberculous pleurisy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Aortic injury	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Brain contusion	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Chest injury	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Confusion postoperative	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Fractured sacrum	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Incarcerated incisional hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Laceration	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Periorbital haematoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Post procedural haematuria	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Stomal hernia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Subarachnoid haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.15% 5/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Traumatic haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Wound evisceration	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Arthroscopy	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Blood creatinine increased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Ecg signs of myocardial ischaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Haemoglobin decreased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Heart rate abnormal	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Liver function test increased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Investigations Platelet count decreased	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Diabetes with hyperosmolarity	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Lactic acidosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Inguinal mass	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell small lymphocytic lymphoma stage iv	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer stage 0, with cancer in situ	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain cancer metastatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the caecum	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large b-cell lymphoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papillary mucinous neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraocular melanoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyosarcoma metastatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Light chain disease	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to pleura	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic renal cell carcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myeloproliferative neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-hodgkin's lymphoma	0.04% 1/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal cancer metastatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Paraneoplastic syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.09% 3/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Throat cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid adenoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vocal cord neoplasm	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Autonomic nervous system imbalance	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Balance disorder	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Basal ganglia haemorrhage	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Carotid artery stenosis	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.12% 4/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Carpal tunnel syndrome	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebellar infarction	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.06% 2/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Cerebral artery embolism	0.00% 0/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.00% 0/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	0.03% 1/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)

Other adverse events

Measure	Apixaban, 2.5 or 5 mg Twice Daily n=2798 participants at risk Patients received 5 mg of apixaban twice daily. Participants who fulfilled any 2 of the following criteria at baseline received apixaban, 2.5 mg twice daily: age older than 80 years, body weight of 60 kg or less, Serum creatinine level ≥1.5 mg/dL. Participants randomized to the 2.5 mg twice daily dose of apixaban continued on this dose throughout the study even if they no longer fulfilled the previous criteria.	Acetylsalicylic Acid, 81-324 mg Once Daily n=2780 participants at risk Patients received 81 to 324 mg of acetylsalicylic acid once daily, with dosage based on investigator discretion Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.	Open Label Apixaban n=3275 participants at risk Participants who completed the double-blind treatment period and met eligibility criteria had the option of enrolling in the Long Term Open Label Extension to receive open-label apixaban.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.9% 109/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	5.1% 141/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	5.0% 164/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)
Nervous system disorders Dizziness	3.9% 109/2798 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	5.2% 144/2780 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)	4.0% 132/3275 • From first dose to last dose plus 30 days (assessed up to May 2017, approximately 95 months)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER