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.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.