Drug Interaction Report

MONITOR: Coadministration with strong CYP450 3A4 inhibitors may increase plasma concentrations and the risk of adverse effects of clindamycin, which is metabolized predominantly by the isoenzyme.

MANAGEMENT: Caution is advised if clindamycin is used concomitantly with strong CYP450 3A4 inhibitors. The possibility of adverse reactions to clindamycin should be considered during coadministration with strong CYP450 3A4 inhibitors. Dosage adjustments as well as clinical and laboratory monitoring of clindamycin should be considered whenever a strong CYP450 3A4 inhibitor is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).