Drug Interaction Report

GENERALLY AVOID: Coadministration with letermovir may increase the plasma concentrations of drugs that are CYP450 3A4 substrates, such as bosentan and nevirapine. Additionally, coadministration of letermovir with inducers of the P-glycoprotein (P-gp) efflux transporter and/or the uridine diphosphate glucuronosyltransferase (UGT) enzymes, such as bosentan and nevirapine may decrease the plasma concentrations of letermovir leading to loss of efficacy of letermovir. Drug interaction studies performed to assess the degree of CYP450 3A4 inhibition between letermovir and midazolam (CYP450 3A4 probe substrate) show the net effect of letermovir inhibition on CYP450 3A4 as moderate. According to the product labeling, coadministration of bosentan or nevirapine with letermovir may decrease letermovir plasma concentrations possibly due to P-gp and/or UGT induction.

MANAGEMENT: Coadministration of bosentan or nevirapine with letermovir is not recommended due to the potential loss of efficacy of letermovir. If letermovir is added to or withdrawn from therapy with drugs that are substrates of CYP450 3A4 such as bosentan and nevirapine, dosage adjustments and clinical and laboratory monitoring of bosentan and nevirapine is recommended. Moreover, clinicians should be aware that the magnitude of CYP450 3A-mediated drug interactions with coadministered drugs may be different when letermovir is used with cyclosporine.