Drug Interaction Report

ADJUST DOSE: Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of daclatasvir, which is primarily metabolized by the isoenzyme. In 17 healthy volunteers, administration of daclatasvir 120 mg daily for 4 days during concomitant treatment with the moderate CYP450 3A4 inducer efavirenz (600 mg once daily for 14 days) decreased daclatasvir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 33%, 63% and 17%, respectively, compared to administration of daclatasvir alone at 60 mg daily for 4 days. Linear dose scaling predicted that an increase in the daclatasvir dosage to 90 mg daily when used with efavirenz or other moderate CYP450 3A4 inducers would result in an AUC comparable to that produced by daclatasvir alone at 60 mg daily.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, an increase in the dosage of daclatasvir to 90 mg once daily is recommended when used with moderate CYP450 3A4 inducers.