Drug Interaction Report

MONITOR: Coadministration with inducers of P-glycoprotein (P-gp) or CYP450 3A4 may decrease the plasma concentrations of glecaprevir and pibrentasvir. Both antiviral agents are substrates of the P-gp efflux transporter, and glecaprevir is additionally a substrate of the CYP450 3A4 isoenzyme. When a single 300 mg-120 mg dose of glecaprevir-pibrentasvir was administered to 12 study subjects following multiple dosing of the potent inducer rifampin at 600 mg once daily, glecaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 86% and 88%, respectively, while pibrentasvir Cmax and AUC decreased by 83% and 87%, respectively. Likewise, when a single dose of glecaprevir-pibrentasvir was administered to 10 study subjects following multiple dosing of carbamazepine 200 mg twice daily, glecaprevir Cmax and AUC decreased by approximately two-thirds, while pibrentasvir Cmax and AUC decreased by approximately one-half.

MANAGEMENT: The potential for diminished pharmacologic effects of glecaprevir and pibrentasvir should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of glecaprevir and pibrentasvir. Relative to fasting conditions, mean glecaprevir systemic exposure (AUC) increased by 83% to 163% and mean pibrentasvir AUC increased by 40% to 53% when administered with moderate to high fat meals.

MANAGEMENT: Glecaprevir-pibrentasvir should be administered with food.