Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

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).

Gastric emptying
The results of a study using paracetamol as a marker of gastric emptying suggest that the effect of BYDUREON to slow gastric emptying is minor and not expected to cause clinically significant reductions in the rate and extent of absorption of concomitantly administered oral medicinal products.
Therefore, no dose adjustments for medicinal products sensitive to delayed gastric emptying are required.

When 1,000 mg paracetamol tablets were administered, either 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).

The following interaction studies have been conducted using 10 μg exenatide immediate-release exenatide but not prolonged-release exenatide:

Warfarin
A delay in tmax of about 2 h was observed when warfarin was administered 35 min after immediate- release exenatide. No clinically relevant effects on Cmax or AUC were observed. Increased INR has been spontaneously 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 sections 4.4 and 4.8).

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. e. In 30-week placebo-controlled clinical trials with immediate-release exenatide, 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.

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.

Paediatric population
Interaction studies with exenatide have only been performed in adults.