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.

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.