Patients with renal impairment

Population pharmacokinetic analysis of renal impaired patients receiving 2 mg BYDUREON indicate that there may be an increase in systemic exposure of approximately 74 % and 23 % (median prediction in each group) in moderate (N=10) and mild (N=56) renal impaired patients, respectively as compared to normal (N=84) renal function patients.

Patients with hepatic insufficiency

No pharmacokinetic study has been performed in patients with hepatic insufficiency. Exenatide is cleared primarily by the kidney, therefore hepatic dysfunction is not expected to affect blood concentrations of exenatide.

Gender, race and body weight

Gender, race and body weight have no clinically relevant influence on exenatide pharmacokinetics.

Elderly

Data in elderly are limited, but suggest no marked changes in exenatide exposure with increased age up to about 75 years old.

In a pharmacokinetic study of exenatide twice daily in patients with type 2 diabetes, administration of exenatide (10 µg) resulted in a mean increase of exenatide AUC by 36 % in 15 elderly subjects aged 75 to 85 years compared to 15 subjects aged 45 to 65 years likely related to reduced renal function in the older age group (see section 4.2).

Paediatric population

In a single-dose pharmacokinetic study of exenatide twice daily in 13 patients with type 2 diabetes and between the ages of 12 and 16 years, administration of exenatide (5 μg) resulted in slightly lower mean AUC (16 % lower) and Cmax (25 % lower) compared to those observed in adults. No pharmacokinetics study of BYDUREON has been conducted in the paediatric population.

5.3 Preclinical safety data

 Non-clinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeat-dose toxicity, or genotoxicity conducted with exenatide twice daily or BYDUREON.

In a 104week carcinogenicity study with BYDUREON a statistically significant increase in thyroid c - cell tumour incidence (adenomas and / or carcinomas) was observed in rats at all doses (1.4- to 26-fold the human clinical exposure with BYDUREON). The human relevance of these findings is currently unknown.

Animal studies with exenatide did not indicate harmful effects with respect to fertility; high doses of exenatide caused skeletal effects and reduced foetal and neonatal growth.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

 Powder

poly (D,L-lactide-co-glycolide)

sucrose

Solvent

carmellose sodium

sodium chloride

polysorbate 20

monobasic sodium phosphate, monohydrate

dibasic sodium phosphate, heptahydrate

water for injections

6.2 Incompatibilities

 In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

 2 years

After reconstitution

The suspension must be injected immediately.

6.4 Special precautions for storage

 Store in a refrigerator (2ºC - 8ºC).

Do not freeze.

The kit may be kept for up to 4 weeks below 30ºC prior to use.

Store in the original package in order to protect from light.

6.5 Nature and contents of container

 The powder is packaged i