Liverpool HEP Interactions

Based on drug interaction studies conducted with Epclusa, no clinically significant drug interactions have been observed with darunavir/ritonavir. Coadministration of darunavir/ritonavir (800/100 mg once daily with emtricitabine and tenofovir-DF) and sofosbuvir/velpatasvir (400/100 mg once daily) was studied in 29 subjects. Cmax and AUC of sofosbuvir decreased by 38% and 28%; Cmax, AUC and Cmin of GS-331007 increased by 4%, 13% and 13% respectively. Velpatasvir Cmax and AUC decreased by 24% and 16%, but Cmin increased by 1%. Darunavir Cmax, AUC and Cmin decreased by 10%, 8% and 13%, respectively; ritonavir Cmax, AUC and Cmin increased by 7%, 12% and 9%, respectively.

Epclusa Prescribing Information, Gilead Science Inc., June 2021.

Coadministration of sofosbuvir/velpatasvir (400/100 mg, once daily) with darunavir/ritonavir (800/100 mg once daily, with emtricitabine and tenofovir-DF) was studied in 29 healthy volunteers in a cross-over study. Sofosbuvir AUC and Cmax decreased by 27% and 38%; AUC, Cmax and Cmin of GS-331007 increased by 13%, 4% and 13%, respectively. Velpatasvir AUC and Cmax decreased by 16% and 24%, but Cmin increased by 1%. Darunavir AUC, Cmax and Cmin decreased by 7%, 10% and 13% respectively. Ritonavir AUC, Cmax and Cmin increased by 12%, 7% and 9%, respectively. Sofosbuvir/velpatasvir and darunavir/ritonavir-containing regimens may be coadministered without dose adjustment.

Drug-drug interaction studies between Hepatitis C virus antivirals sofosbuvir/velpatasvir and boosted and unboosted Human Immunodeficiency Virus antiretroviral regimens in healthy volunteers. Mogalian E, Stamm LM, Osinusi A, et al. Clin Infect Dis, 2018, 67(6): 934-940.

Coadministration a single dose of sofosbuvir (400 mg) before and after 10 days of darunavir/ritonavir (800/100 mg once daily) was studied in 18 subjects. Darunavir/ritonavir modestly increased sofosbuvir exposure but had no effect on GS-331007. Sofosbuvir did not affect the pharmacokinetics of darunavir or ritonavir.

No clinically significant pharmacokinetic drug interactions between sofosbuvir (GS-7977) and HIV antiretrovirals Atripla®, rilpivirine, darunavir/ritonavir, or raltegravir in healthy volunteers. Kirby B, et al. Hepatology, 2012, 56(4); 1067A (abstract 1877).

Coadministration of sofosbuvir/velpatasvir (400/100 mg, once daily) with darunavir/ritonavir (800/100 mg, once daily) and emtricitabine/tenofovir-DF (200/300 mg, once daily) was studied in 30 healthy volunteers. Sofosbuvir AUC and Cmax decreased by 27% and 38%, respectively. G-331007 AUC and Ctau both increased by 13%, Cmax increased by 4%. Velpatasvir AUC and Cmax decreased by 16% and 24%, while Ctau increased by 1%. No dosage adjustments are required.

Drug-Drug Interaction Studies Between Hepatitis C Virus Antivirals Sofosbuvir/Velpatasvir and Boosted and Unboosted Human Immunodeficiency Virus Antiretroviral Regimens in Healthy Volunteers. Mogalian E, Stamm L M, Osinusi A et al. Clin Infect Dis, 2018; 67(6): 934-940.