Drug Interaction Report

MONITOR: Coadministration of inhaled ciclesonide with potent inhibitors of CYP450 3A4 may increase systemic bioavailability of the pharmacologically active metabolite, des-ciclesonide, which is a substrate of the isoenzyme. In one study, administration of orally inhaled ciclesonide in combination with the potent inhibitor ketoconazole resulted in an approximately 3.6-fold increase in steady-state des-ciclesonide systemic exposure (AUC), while levels of ciclesonide remained unchanged. In another study, coadministration of orally inhaled ciclesonide with erythromycin, a less potent inhibitor, had no effect on the pharmacokinetics of des-ciclesonide.

MANAGEMENT: Caution is advised if ciclesonide is prescribed with potent CYP450 3A4 inhibitors. Alternatively, a less potent, less lipophilic, and/or shorter-acting agent such as beclomethasone may be considered. Beclomethasone is also less dependent on CYP450 3A4 metabolism. Patients should be monitored for systemic glucocorticoid effects including symptoms of hypercorticism (e.g., acne, easy bruising, moon face, edema, hirsutism, buffalo hump, skin striae, irregular menstruations), adrenal suppression (which reduces patient's ability to respond to stress situations), immunosuppression, osteoporosis, glucose intolerance, and exacerbation of diabetes mellitus.

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.