Coadministration of ledipasvir/sofosbuvir (90/400 mg) and rilpivirine increased ledipasvir AUC, Cmin and Cmax by 2%, 2% and 1%. Sofosbuvir AUC increase by 5% but Cmax decreased by 4%; the AUC, Cmin and Cmax of the sofosbuvir metabolite GS-331007 increased by 8%, 10% and 8%. Rilpivirine AUC, Cmin and Cmax decreased by 5%, 7% and 3%. Coadministration of ledipasvir/sofosbuvir (90/400 mg) and tenofovir alafenamide increased the AUC and Cmax of tenofovir alafenamide by 32% and 3%. No dose adjustment is required.

Based on drug interaction studies conducted with the fixed dose combination or components of Odefsey, no clinically significant drug interactions have been either observed or expected when Odefsey is combined with ledipasvir. Coadministration of ledipasvir/sofosbuvir (90/400 mg once daily) and Odefsey was studied in 42 subjects. Rilpivirine Cmax, AUC and Cmin decreased by 3%, 5% and 7%, respectively. Tenofovir alafenamide Cmax and AUC increased by 3% and 32%. Data from 41 subjects showed ledipasvir Cmax and AUC increased by 1% and 2%, and sofosbuvir Cmax decreased by 4% but AUC increased by 5%; GS-331007 Cmax decreased by 4% and AUC increased by 5%.

Coadministration of ledipasvir/sofosbuvir (90/400 mg) with rilpivirine/emtricitabine/tenofovir alafenamide (25/200/25 mg) was studied in 42 healthy subjects. Ledipasvir AUC, Cmax and Cmin increased by 2%, 1% and 2%, respectively. Sofosbuvir AUC increased by 2% and Cmax decreased by 1%; PK parameters for sofosbuvir metabolites GS566500 and GS-331007 were unchanged. Rilpivirine AUC, Cmax and Cmin decreased by 5%, 3% and 7%, respectively. Emtricitabine AUC was unchanged, Cmax decreased by 3% and Cmin increased by 2%. Tenofovir alafenamide AUC and Cmax increased by 32% and 3%, respectively. Tenofovir AUC, Cmax and Cmin increased 75%, 62%, and 85%, respectively. The authors conclude that the increase in tenofovir exposure is not clinically relevant as 25 mg of tenofovir alafenamide results in exposures ~90% lower than those seen with administration of 300 mg of tenofovir-DF and that ledipasvir/sofosbuvir and rilpivirine/emtricitabine/tenofovir alafenamide can be coadministered safely without dose reduction.