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 enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.