er with or without a meal, following 14 weeks of BYDUREON therapy, no significant changes in paracetamol AUC were observed compared to the control period. Paracetamol Cmax decreased by 16 % (fasting) and 5 % (fed) and tmax was increased from approximately 1 hour in the control period to 1.4 hours (fasting) and 1.3 hours (fed).
Sulphonylureas
The dose of a sulphonylurea may require adjustment due to the increased risk of hypoglycaemia associated with sulphonylurea therapy (see sections 4.2 and 4.4).
The following interaction studies have been conducted using 10 μg exenatide twice daily but not exenatide once weekly:
Interaction studies with exenatide have only been performed in adults.
Hydroxy Methyl Glutaryl Coenzyme A reductase inhibitors
Lovastatin AUC and Cmax were decreased approximately 40 % and 28 %, respectively, and tmax was delayed about 4 h when exenatide twice daily was administered concomitantly with a single dose of lovastatin (40 mg) compared with lovastatin administered alone. In exenatide twice daily 30-week placebo-controlled clinical trials, concomitant use of exenatide and HMG CoA reductase inhibitors was not associated with consistent changes in lipid profiles (see section 5.1). No predetermined dose adjustment is required; however, lipid profiles should be monitored as appropriate.
Warfarin
A delay in tmax of about 2 h was observed when warfarin was administered 35 min after exenatide twice daily. No clinically relevant effects on Cmax or AUC were observed. Increased INR has been reported during concomitant use of warfarin and exenatide twice daily. INR should be monitored during initiation of BYDUREON therapy in patients on warfarin and/or cumarol derivatives (see section 4.8).
Digoxin and lisinopril
In interaction studies of the effect of exenatide twice daily on digoxin and lisinopril there were no clinical relevant effects on Cmax or AUC, however, a delay in tmax of about 2 h was observed.
Ethinyl estradiol and levonorgestrel
Administration of a combination oral contraceptive (30 µg ethinyl estradiol plus 150 µg levonorgestrel) one hour before exenatide twice daily did not alter the AUC, Cmax or Cmin of either ethinyl estradiol or levonorgestrel. Administration of the oral contraceptive 35 minutes after exenatide did not affect AUC but resulted in a reduction of the Cmax of ethinyl estradiol by 45 %, and Cmax of levonorgestrel by 27-41 %, and a delay in tmax by 2-4 h due to delayed gastric emptying. The reduction in Cmax is of limited clinical relevance and no adjustment of dosing of oral contraceptives is required.
4.6 Pregnancy and lactation
Women of childbearing potential
Due to the long washout period of BYDUREON, women of childbearing potential should use contraception during treatment with BYDUREON. BYDUREON should be discontinued at least 3 months before a planned pregnancy.
Pregnancy
There are no adequate data from the use of BYDUREON in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. BYDUREON should not be used during pregnancy and the use of insulin is recommended.
Breastfeeding
It is unknown whether exenatide is excreted in human milk. BYDUREON should not be used during breast-feeding.
Fertility
No fertility studies in humans have been conducted.
4.7 Effects on ability to drive
