Drug Interaction Report

Coadministration with clarithromycin may slightly increase the bioavailability of dabigatran following oral administration of dabigatran etexilate. The proposed mechanism is clarithromycin inhibition of the P-glycoprotein efflux transporter, of which dabigatran etexilate is a substrate. When dabigatran etexilate was coadministered with clarithromycin 500 mg twice a day in healthy volunteers, increases in dabigatran peak plasma concentration (Cmax) by about 15% and systemic exposure (AUC) by about 19% were observed without any clinical safety concern. Dabigatran had no significant effect on the pharmacokinetics of clarithromycin. No dosage adjustment for dabigatran etexilate is recommended during coadministration with clarithromycin, but caution may be advisable.

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.