Drug Interactions between darunavir and Mavyret

GENERALLY AVOID: Coadministration with boosted darunavir or lopinavir/ritonavir may significantly increase the plasma concentrations of glecaprevir. The proposed mechanism is inhibition of organic anion transporting polypeptide (OATP) 1B1-mediated hepatic uptake of glecaprevir by darunavir, lopinavir, and ritonavir. Inhibition of intestinal and/or biliary efflux of glecaprevir via P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may also contribute. When glecaprevir-pibrentasvir 300 mg-120 mg once daily was administered with darunavir 800 mg plus ritonavir 100 mg once daily to 8 study subjects, glecaprevir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) increased by approximately 3.1-, 5.0- and 8.2-fold, respectively. Pibrentasvir Cmax and AUC were unaffected, but Cmin increased by approximately 1.7-fold. Darunavir and ritonavir pharmacokinetics were also impacted, with darunavir Cmax and AUC increasing by approximately 1.3-fold each and ritonavir Cmax and AUC increasing by approximately 2-fold each. When glecaprevir-pibrentasvir 300 mg-120 mg once daily was administered with lopinavir-ritonavir 400 mg-100 mg twice daily to 9 study subjects, glecaprevir Cmax, AUC and Cmin increased by approximately 2.6-, 4.4- and 18.6-fold, respectively, while pibrentasvir Cmax, AUC and Cmin increased by 1.4-, 2.5- and 5.2-fold, respectively. High plasma levels of glecaprevir may increase the risk of adverse effects such as alanine aminotransferase (ALT) and bilirubin elevations.

MANAGEMENT: Concomitant use of glecaprevir with lopinavir-ritonavir or darunavir boosted with either ritonavir or cobicistat is not recommended.