Dolutegravir + Ledipasvir/Sofosbuvir = Unknown or no reaction

Effect on Concentration

Dolutegravir
No change
Applies within class?
No
Ledipasvir/Sofosbuvir
No change
Applies within class?
No

Pharmacologic Effects

Dolutegravir
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

If used with a tenofovir disoproxil fumarate containing NRTI backbone, tenofovir concentrations may rise.

Sources

Dolutegravir versus Ledipasvir/Sofosbuvir ^

Study Design

The objective of this study was to investigate potential pharmacokinetic (PK) interaction between ledipasvir/sofosbuvir (LDV/SOF) and dolutegravir plus emtricitabine/ tenofovir (DTG + FTC/TDF). In phase 1, open-label study, 30 healthy subjects with age of 19-45 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= DTG + FTC/TDF

Study Results

Coadministration of LDV/SOF (90mg/ 400 mg) together with DTG + FTC/TDF (500 mg + 200/300 mg) for 10 days resulted in no significant effect on pharmacokinetic (PK) parameters of LDV, SOF, GS-331007, metabolite of SOF (Table 2), DTG and FTC, whereas significantly increased tenofovir (TFV) PK parameters (Table 3). Table 2. PK parameters [90% CI] of LDV/SOF PK parameters of AUC [90% CI] Cmax [90% CI] Ct [90% CI] LDV 0.89 [0.84, 0.95] 0.85 [0.81, 0.90] 0.89 [0.84, 0.95] SOF 1.09 [1.00, 1.19] 1.06 [0.92, 1.21] GS-331007 1.06 [1.03, 1.09] 0.99 [0.95, 1.03] 1.06 [1.03, 1.10] Table 3. PK parameters [90% CI] of DTG + FTC/TFV PK parameters of AUC [90% CI] Cmax [90% CI] Ct [90% CI] DTG 1.13 [1.06, 1.20] 1.15 [1.07, 1.23] 1.13 [1.06, 1.21] FTC 1.07 [1.04, 1.10] 1.02 [0.95, 1.06] 1.05 [1.02, 1.09] TFV 1.65 [1.59, 1.71] 1.61 [1.51, 1.72] 2.15 [2.05, 2.26]

Study Conclusions

Concomitant use of LDV/SOF and DTG+FTC/TDF may lead to increased plasma concentrations of tenofovir (TFV).1-3 If LDV/SOF is used concomitantly with DTG+FTC/TDF, Increased clinical and laboratory monitoring for TFV-associated adverse effects is recommended.

References

German P, Pang P, West S, Han L, Sajwani K, Matias A. Drug interactions between direct acting anti-hcv antivirals sofosbuvir and ledipasvir and hiv antiretrovirals. International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy . Washingston DC, USA. 15; May 2014.