Drug Interactions between maribavir and tipranavir

MONITOR: Coadministration with maribavir may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) efflux transporters, both of which have been shown to be inhibited in vitro by maribavir at clinically relevant concentrations. Inhibition of transporter-mediated efflux in the intestine and possibly other organs such as the liver and kidney can increase the systemic bioavailability and decrease the clearance of affected substrates. When a single 0.5 mg dose of digoxin, a sensitive P-gp substrate, was coadministered with maribavir 400 mg twice daily in 18 study subjects, mean digoxin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 25% and 21%, respectively, compared to digoxin administered alone. There are no clinical data regarding the use of maribavir with BCRP substrates, but increases in plasma concentrations of sensitive substrates such as rosuvastatin are expected according to the prescribing information.

MANAGEMENT: Caution is advised when maribavir is prescribed with drugs that are P-gp and/or BCRP substrates, particularly sensitive substrates or those with a narrow therapeutic range. Clinical and laboratory monitoring as well as dosage adjustments may be appropriate for some drugs whenever maribavir is added to or withdrawn from therapy. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of coadministration of P-gp/BCRP inhibitors and for any dosage adjustments that may be required.