Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of retapamulin, which is primarily metabolized by the isoenzyme. In healthy adult males, coadministration of the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice a day) increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of retapamulin by 81% following topical application of retapamulin ointment 1% on abraded skin. However, dosage adjustments are not necessary due to the low systemic exposure to retapamulin following topical application.

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.