Epclusa has been shown to increase tenofovir exposure (P-gp-inhibition). The increase in tenofovir exposure (AUC and Cmax) was around 40-80% during co-treatment with Epclusa and tenofovir disoproxil fumarate/emtricitabine as part of various HIV regimens. Patients receiving tenofovir disoproxil fumarate and Epclusa concomitantly should be monitored for adverse reactions associated with tenofovir disoproxil fumarate. Refer to the tenofovir disoproxil fumarate-containing product’s Summary of Product Characteristics for recommendations on renal monitoring. Epclusa has been shown to increase tenofovir exposure, especially when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat). The safety of tenofovir disoproxil fumarate in the setting of Epclusa and a pharmacokinetic enhancer has not been established. The potential risks and benefits associated with co-administration of Epclusa with the fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or tenofovir disoproxil fumarate given in conjunction with a boosted HIV protease inhibitor (e.g. atazanavir or darunavir) should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving Epclusa concomitantly with elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or with tenofovir disoproxil fumarate and a boosted HIV protease inhibitor should be monitored for tenofovir-associated adverse reactions. Refer to tenofovir disoproxil fumarate, emtricitabine/tenofovir disoproxil fumarate, or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate Summary of Product Characteristics for recommendations on renal monitoring.
Epclusa Summary of Product Characteristics, Gilead Sciences Ltd, July 2016.

Coadministration may increase tenofovir concentrations. Monitor for tenofovir-associated adverse reactions in patients receiving Epclusa concomitantly with a regimen containing tenofovir DF. Refer to the prescribing information of the tenofovir DF-containing product for recommendations on renal monitoring.
Coadministration of tenofovir-DF (300 mg once daily with emtricitabine, atazanavir and ritonavir) and sofosbuvir/velpatasvir (400/100 mg once daily) was studied in 24 subjects. Cmax and AUC of sofosbuvir increased by 12% and 22%; Cmax, AUC and Cmin of GS-331007 increased by 21%, 32% and 42% respectively. Velpatasvir Cmax, AUC and Cmin increased by 55%, 142%, and 301%. Tenofovir Cmax, AUC and Cmin increased by 55%, 30% and 39%, respectively.
Coadministration of tenofovir-DF (300 mg once daily with emtricitabine, darunavir and ritonavir) 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%. Tenofovir Cmax, AUC and Cmin increased by 55%, 39% and 52%, respectively.
Coadministration of tenofovir-DF (300 mg once daily with emtricitabine and efavirenz) and sofosbuvir/velpatasvir (400/100 mg once daily) increased sofosbuvir Cmax by 38% but decreased AUC by 3%; Cmax and AUC of GS-331007 decreased by 14% and 10%, but Cmin increased by 1%; velpatasvir Cmax, AUC and Cmin decreased by 47%, 53% and 57%, respectively (n=14). Tenofovir Cmax, AUC and Cmin increased by 77%, 81% and 121%, respectively (n=15).
Coadministration of tenofovir-DF (300 mg once daily with elvitegravir/cobicistat/emtricitabine) and sofosbuvir/velpatasvir (400/100 mg once daily) was studied in 24 subjects. Cmax and AUC of sofosbuvir increased by 1% and 24%; Cmax, AUC and Cmin of GS-331007 increased by 13%, 35% and 45% respectively. Velpatasvir Cmax, AUC and Cmin increased by 5%, 19% and 37%, respectively. Tenofovir Cmax, AUC and Cmin increased by 36%, 35% and 45%, respectively.
Coadministration of tenofovir-DF (300 mg once daily with emtricitabine and rilpivirine) and sofosbuvir/velpatasvir (400/100 mg once daily) was studied in 24 subjects. Tenofovir Cmax, AUC and Cmin increased by 44%, 40% and 84%, respectively. No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 or velpatasvir was observed with the combination of emtricitabine, rilpivirine, and tenofovir DF.
Coadministration of tenofovir-DF (300 mg twice daily with emtricitabine and raltegravir) and sofosbuvir/velpatasvir (400/100 mg once daily) increased tenofovir Cmax, AUC and Cmin by 46%, 40% and 70%, respectively (n=30). No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 or velpatasvir was observed.
Coadministration of tenofovir-DF (300 once daily with lopinavir, ritonavir and emtricitabine) and sofosbuvir/velpatasvir (400/100 mg once daily) was studied in 24 subjects. Cmax and AUC of sofosbuvir decreased by 41% and 29%. Cmax, AUC and Cmin of GS-331007 increased by 1%, 15% and 15%, respectively. Velpatasvir Cmax decreased by 30%, but AUC and Cmin increased by 2% and 63%.
No effect on the pharmacokinetic parameters of sofosbuvir, GS-331007 or velpatasvir was observed with tenofovir DF.
Epclusa US Prescribing Information, Gilead Sciences Inc, June 2016.