Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. In 10 study subjects, administration of a single 50 mg dose of doravirine with the potent CYP450 3A4 inhibitor ritonavir (100 mg twice daily) increased doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) by an average of 31%, 254% and 191%, respectively, compared to administration of doravirine alone. When a single 100 mg dose of doravirine was administered with ketoconazole 400 mg once daily in 10 study subjects, doravirine Cmax, AUC and C24hr increased by an average of 25%, 206% and 175%, respectively. These changes are not considered clinically significant.

MONITOR: Due to their gastrointestinal pharmacologic effects, somatostatin analogs (e.g., octreotide, lanreotide) may variously affect the absorption of dietary nutrients and concomitantly administered oral medications. Somatostatin analogs have been shown to prolong gastrointestinal transit time and inhibit intestinal absorption of some nutrients such as fat. Clinical data are limited, however. In case reports, octreotide has been reported to reduce the relative bioavailability of cyclosporine. Transplant rejection and significant reductions in cyclosporine levels, sometimes to undetectable levels, have been reported in association with the interaction. Vitamin K absorption was not affected when concomitantly administered with lanreotide according to the manufacturer.

MANAGEMENT: Clinicians should be aware of the potential for altered absorption of concomitantly administered oral medications during treatment with somatostatin analogs. Blood levels and clinical response should be monitored, particularly for drugs that have a narrow therapeutic index, and the dosages adjusted as necessary.