Tenofovir Disoproxil Fumarate + Faldaprevir = Precautionary

Effect on Concentration

Tenofovir Disoproxil Fumarate
No change
Applies within class?
No
Faldaprevir
Decrease
Applies within class?
No

Pharmacologic Effects

Tenofovir Disoproxil Fumarate
Effect
N/A
Applies within class?
No
Faldaprevir
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 11-Jul-2018

Summary

Sources

Clinical assessment of potential drug interactions of faldaprevir, a hepatitis C virus protease inhibitor, with darunavir/ritonavir, efavirenz, and tenofovir. ^

Study Design

FDV (faldaprevir) interactions with DRV/r (darunavir/ritonavir), EFV (efavirenz), and TDF (tenofovir) were assessed in three open-label, Phase I trials in healthy volunteers (HV). Trial 1: 14 HV received DRV/r 800/100mg once daily on days 1-16, a loading dose of FDV 480mg on day 9, and FDV 240mg once daily on days 10-16. Trial 2: 15 HV received a loading dose of FDV 480mg on day 2, FDV 240mg twice daily on days 3-18, EFV 600mg once daily on days 10-18, and oral MDZ (midazolam) 7.5mg once daily as a probe substrate on days 1, 9, and 18. Trial 3: 16 HV received TDF 300mg once daily on days 1-15, a loading dose of FDV 480mg on day 8, and FDV 240mg twice daily on days 9-22. Plasma levels of FDV, DRV, MDZ, and TFV were collected. Geometric mean ratios (GMR) for steady-state AUCs assessed interaction potential and minimum/maximum concentrations.

Study Results

Co-administered drug GMR (90% CI) of FDV PK parameter (with/without co-administered drug) N Cmax AUC Cmin FDV + DRV/r 14 Increase 64% (gMean % change) Increase 129% (gMean % change) Increase 283% (gMean % change) FDV + EFV + MDZ 15 0.72 (0.61-0.84) 0.65 (0.53-0.79) 0.54 (0.40-0.73) FDV + TDF 16 0.82 (0.72-0.93) 0.78 (0.71-0.85) 0.75 (0.69-0.83) GMR (90% CI) of co-administered drug PK parameter (with/without FDV) Cmax AUC Cmin DRV/r + FDV 14 1.28 (1.16-1.43) 1.15 (1.01-1.31) 0.88 (0.69-1.13) MDZ (with FDV) 15 1.11 (0.85-1.44) 2.24 (1.87-2.69) - MDZ (with FDV + EFV) 14 0.41 (0.27-0.62) 0.39 (0.30-0.51) - TDF + FDV 16 0.95 (0.85-1.05) 1.22 (1.12-1.33) 1.47 (1.35-1.61)

Study Conclusions

Interim data from the phase 3 STARTVerso4 trial in HIV/HCV co-infected patients, FDV (240mg daily) did not have an effect on EFV C12 levels, 92.69 (84.19, 102.04) (adjusted gMean ratio, % (90% CI)). ***Caution is warranted when co-administering FDV with DRV/r, TDF, or EFV. FDV exposures have been shown to increase 130% with DRV/r and decrease 22% with TDF. FDV with EFV has resulted in 35% decreased FDV exposure, likely due to CYP3A4 induction.

References

Sabo JP, Kort J, Ballow C, Maschke M, Battegay M, Fuhr R, Li Y. Clinical assessment of potential drug interactions of faldaprevir, a hepatitis c virus protease inhibitor, with darunavir/ritonavir, efavirenz, and tenofovir. Clinical Infectious Diseases. 2014; 10: 1420-1428.