No studies on the effects of the ability to drive and use machines have been performed. When BYDUREON is used in combination with a sulphonylurea, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines.

4.8 Undesirable effects

 Summary of the safety profile

The most frequent adverse drug reactions ( 5 % of BYDUREON treatment) were mainly gastrointestinal related (nausea, vomiting, diarrhoea and constipation). The most frequently reported single adverse reaction was nausea which was associated with the initiation of treatment and decreased over time. In addition, injection site reactions (pruritus, nodules, erythema), hypoglycaemia (with a sulphonylurea), and headache occurred. Most adverse reactions associated with BYDUREON were mild to moderate in intensity.

Acute pancreatitis and acute renal failure have been reported rarely since exenatide twice daily has been marketed (see section 4.4).

Tabulated summary of adverse reactions

The frequency of adverse reactions of BYDUREON with an incidence of  1 % are summarised in Table 1 below.

The data source comprises two placebo controlled studies (10 and 15 weeks) and 3 trials comparing BYDUREON to either exenatide twice daily (a 30 week study), sitagliptin and pioglitazone (a 26 week study) and insulin glargine (a 26 week study). Background therapies included diet and exercise, metformin, a sulphonylurea, a thiazolidinedione or a combination of oral anti-diabetic agents.

The adverse reactions observed from post-marketing and clinical trial experience with exenatide twice daily that were not observed with BYDUREON at an incidence of  1 % are listed in Table 2 below.

The reactions are listed below as MedDRA preferred term by system organ class and absolute frequency. Patient frequencies are defined as: very common ( 1/10), common ( 1/100 to < 1/10), uncommon ( 1/1000 to < 1/100), rare ( 1/10000 to < 1/1000) and very rare (< 1/10000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Table 1: The frequency of adverse reactions of BYDUREON with an incidence of  1 % in clinical trials. n= 592 total, (patients on sulphonylurea n= 135)

Very common
 Common
 
Metabolism and nutrition disorder
 
Hypoglycaemia (with a sulphonylurea)1
 Decreased appetite 1
 
Nervous system disorders
 
 
 Dizziness 1
 
 
 Headache 1
 
Gastrointestinal disorders
 
Constipation
 Abdominal distention
 
Diarrhoea1
 Abdominal pain 1
 
Nausea1
 Dyspepsia 1
 
Vomiting1
 Eructation
 
 
 Flatulence 1
 
 
 Gastroesophageal reflux 1
 
General disorders and administration site conditions
 
Injection site pruritus
 Fatigue 1
 
 
 Injection site erythema
 
 
 Injection site rash
 
 
 Somnolence
 

1 Frequency of reactions was the same in the exenatide twice daily treatment group.

Table 2: The adverse reactions observed from post-marketing and clinical trial experience with exenatide twice daily that were not observ