Drug Interaction Report

Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of fidaxomicin and its main metabolite, OP-1118, both of which are substrates of the intestinal efflux transporter. When fidaxomicin 200 mg was administered in combination with cyclosporine 200 mg in 14 study subjects, fidaxomicin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by an average of 4.2- and 1.9-fold, respectively, compared to when administered alone. The Cmax and AUC of OP-1118 was increased by 9.5- and 4.1-fold, respectively, with cyclosporine. Theoretically, concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) due to P-gp inhibition. However, concomitant use of a P-gp inhibitor had no attributable effect on safety or efficacy of fidaxomicin in controlled clinical trials. No dosage adjustment is recommended when fidaxomicin is coadministered with P-gp inhibitors.