Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide + Ledipasvir/Sofosbuvir = Precautionary

Effect on Concentration

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide
No change
Applies within class?
No
Ledipasvir/Sofosbuvir
Increase
Applies within class?
No

Pharmacologic Effects

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide
Effect
N/A
Applies within class?
No
Ledipasvir/Sofosbuvir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 18-Jul-2018

Summary

Sources

Elvitegravir/Cobicistat/Emtricitabine/Tenofovir AF versus Ledipasvir/Sofosbuvir ^

Study Design

The objective of this study was to investigate potential pharmacokinetic (PK) interaction between ledipasvir/sofosbuvir (LDV/SOF) and elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF). In phase 1, open-label study, 30 healthy subjects with age of 22-44 years old were randomized to one of the six treatment sequences (table 1). Table 1. Treatment sequence Days 1-10 Days 11-20 Days 21-30 LDV/SOF ARVs LDV/SOF + ARVs LDV/SOF LDV/SOF + ARVs ARVs ARVs LDV/SOF + ARVs LDV/SOF ARVs LDV/SOF LDV/SOF + ARVs LDV/SOF + ARVs ARVs LDV/SOF LDV/SOF + ARVs LDV/SOF ARVs ARVs= E/C/F/TAF

Study Results

Coadministration of LDV/SOF (90mg/ 400 mg) together with E/C/F/TAF (150 mg/ 150 mg/ 200 mg/ 10 mg) for 10 days resulted in significantly increased pharmacokinetic (PK) parameters of LDV, SOF, GS-331007 (metabolite of SOF) (Table 2), elvitegravir (EVG), cobicistat (COBI), and tenofovir (TFV) (Table 3), whereas no significant effect on PK parameters of emtricitabine (FTC) and tenofovir alafenamide (TAF; prodrug of TFV) (Table 3). Table 2. PK parameters [90% CI] of LDV/SOF PK parameters of AUC [90% CI] Cmax [90% CI] Ct [90% CI] LDV 1.79 [1.63, 1.96] 1.65 [1.53, 1.78] 1.93 [1.74, 2.15] SOF 1.47 [1.35, 1.59] 1.28 [1.13, 1.47] GS-331007 1.48 [1.44, 1.53] 1.29 [1.24, 1.35] 1.66 [1.60, 1.73] Table 3. PK parameters [90% CI] of E/C/F/TAF PK parameters of AUC [90% CI] Cmax [90% CI] Ct [90% CI] EVG 1.11 [1.02, 1.20] 0.98 [0.90, 1.07] 1.46 [1.28, 1.66] COBI 1.53 [1.45, 1.62] 1.23 [1.15, 1.32] 3.25 [2.88, 3.67] FTC 0.97 [0.93, 1.00] 1.03 [0.96, 1.11] 0.95 [0.91, 0.99] TFV 1.27 [1.23, 1.31] 1.17 [1.12, 1.22] 1.33 [1.28, 1.38] TAF 0.86 [0.78, 0.95] 0.90 [0.73, 1.11]

Study Conclusions

Concomitant use of LDV/SOF and E/C/F/TAF may result in increased PK parameters of both anti-HCV DAA agents (LDV and SOF) and antiretrovirals (ARVs; EVG, COBI, and TFV). Although investigators concluded that the magnitude of these interactions are not considered clinically relevant, the combination of LDV/ SOF and E/C/F/TAF is not recommended by both NIH guidelines and manufacturer of Harvonidue to lack of safety data.

References

Doyle E, Custodio J, Pang PS, Das M, Cao H, Ma G, Zack J. Lack of drug interactions between boosted and unboosted tenofovir alafenamide-based antiretroviral single tablet regimens (emtricitabine/rilpivirine/tenofovir alafenamide and elvitegravir/cobicistat/e. Open Forum Infectious Diseases. 2015; 1: .