Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate + Ledipasvir/Sofosbuvir = Unknown or no reaction

Effect on Concentration

Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate
No change
Applies within class?
No
Ledipasvir/Sofosbuvir
No change
Applies within class?
No

Pharmacologic Effects

Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate
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

Lack of Drug Interactions Between Boosted and Unboosted Tenofovir Alafenamide-Based Antiretroviral Single Tablet Regimens (Emtricitabine/Rilpivirine/Tenofovir Alafenamide and Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide) and the Anti-HCV Single Tablet Regimen Ledipasvir/Sofosbuvir. ^

Study Design

This was a multiple-dose, randomized, cross-over drug-drug interaction study. Healthy subjects (n=32, fed) received LDV/SOF 90/400mg alone followed by co-administration with RPV/FTC/TDF as 25/200/300mg QD or vice versa, for 10 days. LDV, SOF, GS-331007 (predominant circulating nucleoside metabolite), FTC, tenofovir (TFV), and RPV plasma concentrations were analyzed on the last day of dosing for each treatment and PK parameters were calculated. Geometric least-squares means ratios (GMR) and 90% confidence intervals (90% CI) (combination vs. alone) for LDV, SOF, GS-331007, FTC, TFV, and RPV AUCtau, Cmax and Ctau were estimated and compared against pre-specified lack of PK alteration boundaries of 70-143%.

Study Results

Results showed that LDV/SOF, RPV and FTC PK was not affected by co-administration, however, TFV exposure increases (~1.3-1.9-fold) were observed with LDV/SOF. The GMR (90% CI) for: AUCtau, Cmax and Ctau were as follows: 1.08 (1.02-1.15), 1.01 (0.95-1.07) and 1.16 (1.08-1.25), respectively, for LDV, and 1.15 (1.11-1.19), 1.06 (1.01-1.11) and 1.18 (1.13-1.23), respectively for GS-331007. AUC and Cmax for SOF were 1.10 (1.01-1.21) and 1.05 (0.93-1.20), respectively. AUC, Cmax and Ctau for RPV were 1.02 (0.94-1.11), 0.97 (0.88-1.07) and 1.12 (1.03-1.21), respectively. Those for FTC were 1.04 (1.02-1.08), 1.02 (0.98-1.06) and 1.06 (0.97-1.15), and those for TFV were 1.40 (1.31-1.50) 1.32 (1.25-1.39) and 1.91 (1.74-2.10), respectively.

Study Conclusions

The authors stated that TDF absolute AUC values in the test (combination) treatments were comparable to those achieved when FTC/TDF is administered with ritonavir-boosted PIs, which do not warrant dose adjustment, thus they concluded that LDV/SOF may be co-administered with RPV/FTC/TDF without dose adjustment.

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: .