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and laboratory monitoring of clindamycin should be considered whenever a strong CYP450 3A4 inhibitor is added to or withdrawn from therapy.

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.