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and laboratory monitoring of clindamycin should be considered whenever a strong CYP450 3A4 inhibitor is added to or withdrawn from therapy.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: Food significantly increases the absorption of saquinavir.

MONITOR: Coadministration with grapefruit juice may increase the plasma concentrations of saquinavir. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In eight healthy volunteers, ingestion of 400 mL of grapefruit juice prior to administration of a 600 mg dose of saquinavir mesylate increased the area under the plasma concentration-time curve and oral bioavailability of saquinavir by 50% and 100%, respectively, compared to water; however, the increase is not considered clinically relevant. A high degree of intersubject variability in the grapefruit juice effect was also observed. The extent to which this interaction may occur with the saquinavir free base soft gelatin capsule is unknown. However, the saquinavir soft gelatin capsule formulation is no longer commercially available.

MANAGEMENT: Saquinavir mesylate should be taken with meals or within 2 hours after eating to enhance bioavailability. Patients should be advised to avoid the consumption of large amounts of grapefruit and grapefruit juice during saquinavir therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation.