Coadministration of elbasvir/grazoprevir and OATP1B inhibitors such as cobicistat is contraindicated because it may significantly increase grazoprevir plasma concentrations. Coadministration of a fixed dose combination of elvitegravir/cobicistat/emtricitabine/tenofovir-DF (150/150/200/300 mg once daily) and elbasvir/grazoprevir (50/100 mg once daily) was studied. Elbasvir AUC, Cmax and C24 increased by 118%, 91% and 138% (CYP3A and OATP1B inhibition); grazoprevir AUC, Cmax and C24 increased by 5.36-, 4.59- and 2.78-fold, respectively (CYP3A and OATP1B inhibition). Elvitegravir AUC, Cmax and C24 increased by 10%, 2% and 31%, respectively. Cobicistat AUC and Cmax increased by 49% and 39%. Emtricitabine AUC and C24 increased by 7% and 19%, but Cmax decreased by 4%. Tenofovir AUC, Cmax and C24 increased by 18%, 25% and 20%.

Coadministration of elbasvir/grazoprevir with cobicistat-containing regimens may increase the concentrations of elbasvir and grazoprevir. Co-administration is not recommended. Coadministration of a fixed dose combination of elvitegravir/cobicistat/emtricitabine/tenofovir-DF (150/150/200/300 mg once daily) and elbasvir/grazoprevir (50/100 mg once daily) was studied in 21 subjects. Elbasvir AUC, Cmax and C24 increased by 118%, 91% and 138%; grazoprevir AUC, Cmax and C24 increased by 5.36-, 4.59- and 2.78-fold, respectively. In 22 subjects, elvitegravir AUC, Cmax and C24 increased by 10%, 2% and 31%, respectively. Cobicistat AUC and Cmax increased by 49% and 39%. Emtricitabine AUC and C24 increased by 7% and 19%, but Cmax decreased by 4%. Tenofovir AUC, Cmax and C24 increased by 18%, 25% and 20%.

Coadministration of elbasvir/grazoprevir (50/100 mg once daily) and elvitegravir/cobicistat/emtricitabine/tenofovir-DF (150/150/300/150 mg once daily) was studied in 22 HIV/HCV-negative subjects. Elbasvir AUC, Cmax and Cmin increased by 118%, 91% and 138%; grazoprevir AUC, Cmax and Cmin increased by 436%, 359% and 178%. There were no clinically meaningful effects on elvitegravir AUC, Cmax and Cmin (10%, 2% and 31% increase), cobicistat AUC and Cmax (49% and 39% increase), emtricitabine AUC, Cmax or Cmin (7% increase, 4% decrease, 19% increase) or tenofovir AUC, Cmax and Cmin (18%, 25% and 20% increase). Coadministration is not recommended due to the substantial increase in grazoprevir exposure.