Faldaprevir + Ethinylestradiol/Levonorgestrel = Unknown or no reaction

Effect on Concentration

Faldaprevir
No change
Applies within class?
No
Ethinylestradiol/Levonorgestrel
Increase
Applies within class?
No

Pharmacologic Effects

Faldaprevir
Effect
N/A
Applies within class?
No
Ethinylestradiol/Levonorgestrel
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 22-Nov-2022

Summary

Co-administration of FDV and a combination of EE and LNG resulted in a mild-non-clinically relevant increase in exposure to EE and LNG. Faldaprevir is a weak inhibitor of metabolism for EE in combination with LNG. Increases in bilirubin concentrations with the 240 mg FDV QD dose were predominantly unconjugated, reversible and not associated with markers of liver injury. This is expected with FDV, which is in an inhibitor of UGT1A1, but is expected to be lower in the 120 mg daily dose of FDV that is currently under clinical investigation. No dose adjustment is needed when co-administering a combination of oral contraceptive containing EE and LNG (Seasonique) with FDV.

Sources

Faldaprevir vs ethinylestradiol/levonorgestrel ^

Study Design

Sabo, et al designed an open-label, 2-period, fixed sequence trial that was run in 16 healthy pre-menopausal women. Subjects underwent a run-in period (starting between days -56 and -28), and received 30 mcg ethinylestradiol (EE)/ 150 mcg levonorgestrel (LNG)daily until day -8. No treatment was administered on days -7 to -1 to induce withdrawl bleeding. In period one, subjects received 30 mcg EE / 150 mcg LNG on days 1-13 and received 30 mcg EE / 150 mcg LNG daily with a loading dose of 480 mg faldaprevir (FDV) on day 1 and 240 mg FDV on days 2-8). Pharmacokinetic profiling was done on days 13 and 21.

Study Results

Co-administration of FDV resulted in modest increases in peak, total and trough exposure to EE and LNG and prolonged median T ½ , lower mean oral clearance and apparent volume of distribution of EE and LNG.PK ParameterGMR %90 % CIEthinylestradiolAUC (pg*h/ml)141133.8-148.5Cmax (pg/ml)114.8105.5-125Cmin (pg/ml)171.4160.2-183.3LevonorgestrelAUC (ng*h/ml)140.5136.4 -144.8Cmax (ng/ml)115.3110.8-119.9Cmin (pg/ml)153.9146-162.1Median half-lives were prolonged for both ethinylestradiol (2.4 hours longer) and levonorgestrel (4.7 hours longer) and mean oral clearance and apparent volume of distribution were of both ethinylestradiol and levonorgestrel were lower (approximately 30%) when coadministered with faldaprevir.

Study Conclusions

References

Sabo JB, B Lang, M Elgadi, F Huang. Effect of multiple oral doses of faldeprevir on the multiple dose pharmacokinetics of a combination oral tablet of ethinylestradiol and levonorgestrel in healthy premenopausal female volunteers. abstr. 64rd Annual Meeting Of The American Association For The Study Of Liver Diseases. Washington DC. ; 2013.