Decreased Ledipasvir and Increased Tenofovir concentrations were seen. Monitoring is recommended, but dose alterations are not.
Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate versus Ledipasvir/Sofosbuvir
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Study Design
The drug-drug interaction potential of ledipasvir/sofosbuvir (LDV/SOF) with efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) was assessed in a pharmacokinetic (PK) evaluation. LDV/SOF was administered as 90/400mg QD and EFV/FTC/TDF as 600/200/300mg QD.
Study Results
Co-administration of LDV/SOF with EFV/FTC/TDF resulted in decreased exposure of LDV. Using geometric mean ratios and 90% confidence intervals, the LDV AUC, Cmax and Cmin were 0.66 (0.59-0.75), 0.66 (0.59-0.75) and 0.66 (0.57-0.76), respectively during coadministration.
The magnitude of change in PK parameters for SOF were as follows: Cmax and AUC of 1.03 (0.87-1.23) and 0.94 (0.81-1.10), respectively, and for GS-331007 (major circulating metabolite): Cmax, AUC and Cmin of 0.86 (0.76-0.96), 0.90 (0.83-0.97) and 1.07 (1.02-1.13), respectively.
LDV/SOF did not have a significant effect on the exposure of EFV and FTC PK, however, it was found to increase exposure of tenofovir. Cmax, AUC and Cmin were 1.79 (1.56-2.04), 1.98 (1.77-2.23) and 2.63 (2.32-2.97) for tenofovir, respectively, 0.88 (0.79-0.97), 0.90 (0.84-0.96) and 0.91 (0.83-0.99) for EFV, and 1.08 (0.97-1.21), 1.05 (0.98-1.11) and 1.03 (0.98-1.11), respectivley, for FTC when co-administered with LDV/SOF.
Study Conclusions
The manufacturer states that EFV/FTC/TDF may be co-administered with LDV/SOF. Monitoring for tenofovir-associated adverse effects is advised when this combination is utilized.
References
German P, Pang P, West S, Han L, Sanjwani K, Mathias A. Drug interactions between direct acting anti-hcv antivirals sofosbuvir and ledipasvir and hiv antiretrovirals. International Workshop On Clinical Pharmacology Of Hiv And Hepatitis T Herapy . Washington DC, USA. 15; May 2014.
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