Drug Interaction Report

MONITOR: Coadministration with fenofibrate may increase the plasma concentrations and risk of adverse effects of drugs that are substrates of CYP450 2C19, 2A6, and 2C9 isoenzymes. The proposed mechanism, based on in vitro data, is decreased clearance due to fenofibrate-mediated inhibition of CYP450 2C19, 2A6, and 2C9.

MANAGEMENT: Until more information is available, caution is advised if fenofibrate is used concomitantly with drugs that are substrates of CYP450 2C19, 2A6, or 2C9 isoenzymes, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever fenofibrate is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

ADJUST DOSING INTERVAL: Food, particularly high-fat food, significantly enhances the oral absorption and bioavailability of atovaquone. In 16 healthy volunteers, administration of a single 750 mg dose of atovaquone suspension following a standard breakfast (23 g fat: 610 kCal) resulted in an approximately 3.4-fold increase in the mean peak plasma concentration (Cmax) and a 2.5-fold increase in the mean area under the plasma concentration-time curve (AUC) of atovaquone compared to administration following an overnight fast. In a study consisting of 19 HIV-infected volunteers receiving atovaquone suspension 500 mg/day, Cmax and AUC of atovaquone increased by 72% and 66%, respectively, in the fed state relative to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atovaquone products (suspension, tablet, or in combination with proguanil) should be administered with a meal or milky drink, or enteral nutrition at the same time(s) each day. Because plasma atovaquone concentrations have been shown to correlate with the likelihood of successful treatment and in some cases, survival, alternative therapies may be appropriate for patients who have difficulty taking atovaquone with food.