Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate + Sofosbuvir = Precautionary

Effect on Concentration

Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate
Increase
Applies within class?
No
Sofosbuvir
Decrease
Applies within class?
No

Pharmacologic Effects

Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate
Effect
N/A
Applies within class?
No
Sofosbuvir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 16-Jul-2018

Summary

Decrease in ledipasvir concentrations and increase in tenofovir possible. No dose adjustments necessary, but monitoring for adverse events is recommended.

Sources

Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate versus Sofosbuvir ^

Study Design

In a Phase 1, fixed sequence, 4-cohort study, healthy volunteers received a single dose of sofosbuvir (SOF) 400 mg before and after 14 days of Atripla (ATR, efavirenz (EFV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) 600/200/300 mg QD; n=17, fasted). Geometric means ratio % (GMR%, combination vs alone) of PK parameters AUCinf and Cmax for SOF and GS-331007 (circulating nucleoside metabolite of SOF), or AUCtau, Cmax, and Ctau for tenofovir (TFV), FTC and EFV were evaluated against a predetermined 70-143% equivalence boundary. In a separate study, the drug-drug interaction potential of SOF with efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) was assessed in a PK evaluation. SOF was administered as ledipasvir/sofosbuvir (LDV/SOF) 90/400mg QD and EFV/FTC/TDF as 600/200/300mg QD.

Study Results

In the Phase 1 study, SOF was well tolerated overall, with very few treatment-emergent events during the administration of SOF with EFV/FTC/TDF. Co-administration did not result in clinically significant changes in SOF and/or GS- 331007 exposure. EFV/FTC/TDF slightly decreased SOF and GS- 331007 Cmax (~20 -23%). SOF slightly increased TFV Cmax (~25%), and had no other effect on PK parameters of FTC, TFV, or EFV. In the other study, co-administration of EFV/FTC/TDF with LDV/SOF resulted in a change in Cmax and AUC of 1.03 (0.87-1.23) and 0.94 (0.81-1.10), respectively, for SOF, and 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, for GS-331007.

Study Conclusions

According to the prescribing information for Sovaldi (SOF) and Harvoni (LDV/SOF), no relevant changes in SOF or EFV PK were observed when SOF +/-LDV was co-administered with EFV. *Monitoring for tenofovir-associated adverse effects is advised when EFV/FTC/TDF is administered with combination LDV/SOF.

References

Kirby B, Mathias A, Rossi S. No clinically significant pharmacokinetic drug interactions between sofosbuvir (gs-7977) and hiv antiretrovirals atripla, rilpivirine, drunavir/ritonavir, or raltegravir in healthy volunteers. Hepatology. 2012; 4: 1067A.