Drug Interaction Report

MONITOR: Coadministration with letermovir may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. In vitro and in vivo studies have shown that both estrogens and progestins are partially metabolized by CYP450 3A4. Studies of letermovir with midazolam, a CYP450 3A4 probe substrate, have shown the net effect of letermovir on the CYP450 3A4 isoenzyme is moderate inhibition. Theoretically, concomitant administration of letermovir with CYP450 3A4 substrates, such as estrogens and progestins, may result in clinically relevant increases in the plasma concentration of the CYP450 3A4 substrate. The interaction between letermovir and ethinyl estradiol and levonorgestrel has been evaluated in clinical drug-drug interaction studies and no clinically significant interaction was found.

MANAGEMENT: Monitor estrogen/progestin therapy for altered pharmacologic response and adjust dosage(s) accordingly whenever letermovir is added to or withdrawn from therapy. When choosing an oral contraceptive, consider choosing an ethinyl estradiol-levonorgestrel product as this combination has been studied with letermovir and no clinically significant interaction has been found.