Drug Interactions between AccessPak for HIV PEP Basic and ledipasvir / sofosbuvir

MONITOR: Coadministration with ledipasvir may increase the plasma concentrations of tenofovir. The mechanism of interaction has not been established. In 15 healthy volunteers, administration of a fixed-dose combination product containing efavirenz/emtricitabine/tenofovir disoproxil fumarate 600 mg/200 mg/300 mg once daily concomitantly with ledipasvir-sofosbuvir 90 mg-400 mg once daily resulted in increases of tenofovir peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 79%, 98% and 163%, respectively, and decreases of ledipasvir Cmax, AUC and Cmin by 34% each. When a fixed-dose combination product containing emtricitabine/rilpivirine/tenofovir disoproxil fumarate 200 mg/25 mg/300 mg was administered once daily with ledipasvir-sofosbuvir 90 mg-400 mg once daily to 14 healthy volunteers, tenofovir Cmax, AUC and Cmin increased by 32%, 40% and 91%, respectively, with no changes in ledipasvir or sofosbuvir pharmacokinetics. Increased plasma levels of tenofovir may potentiate the risk of adverse effects such as nephrotoxicity (acute renal failure, Fanconi syndrome), hepatotoxicity (lactic acidosis/hepatomegaly with steatosis), and bone mineral density decreases.

MANAGEMENT: When ledipasvir-sofosbuvir is used with efavirenz/emtricitabine/tenofovir DF, the potential for increased adverse reactions of tenofovir should be considered and patients should be closely monitored. The safety of increased tenofovir concentrations in the presence of ledipasvir-sofosbuvir and a HIV protease inhibitor/ritonavir combination (e.g., atazanavir/ritonavir or darunavir/ritonavir or lopinavir/ritonavir + emtricitabine/tenofovir DF) has not been established. The potential risks and benefits associated with coadministration of ledipasvir-sofosbuvir with tenofovir should be considered, particularly in patients at risk for renal dysfunction. Alternative hepatitis C or antiretroviral therapy should be considered if possible; otherwise, patients should be monitored for tenofovir-related adverse effects. Coadministration of ledipasvir-sofosbuvir and elvitegravir/cobicistat/emtricitabine/tenofovir DF is also not recommended, as safety of increased tenofovir concentrations in this setting has not been established.

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