Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ivermectin and the risk of adverse effects. The proposed mechanism, based on in vitro data, is decreased clearance due to inhibition of CYP450 3A4, the primary isoenzyme responsible for the metabolic clearance of ivermectin.

MANAGEMENT: Caution is advised when ivermectin must be used concomitantly with potent CYP450 3A4 inhibitors. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a potent CYP450 3A4 inhibitor is added to or withdrawn from therapy.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.