Fostemsavir + Ethinylestradiol/Norgestimate = Precautionary

Effect on Concentration

Fostemsavir
No change
Applies within class?
No
Ethinylestradiol/Norgestimate
Increase
Applies within class?
No

Pharmacologic Effects

Fostemsavir
Effect
N/A
Applies within class?
No
Ethinylestradiol/Norgestimate
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 23-Jul-2018

Summary

Sources

Fostemsavir versus Ethinylestridiol/Norgestimate ^

Study Design

AI438019 was a Phase 1, open-label, single-sequence, 4-cycle, 4-treatment study in 26 healthy female subjects. Serial blood samples for PK up to 24 hours post-dose and single samples for serum progesterone were collected. Plasma concentrations were quantified by validated LC/MS/MS methods. Geometric mean ratios (GMRs) and 90% confidence intervals (CI) were derived for EE and NE PK using linear mixed-effects models. Adverse events (AEs) were monitored throughout the study. In cycle one (Treatment A), days 1-8 where day 1 was the 21st day of an existing OC once daily, serum PK collection and serum progesterone were measured on day one. In cycle two (Treatment B), days 1-28, existing OC cycle was given on days 1-21 and serial PK and serum progesterone were measured on day 21. In cycle 3 (Treatment C), Loestrin 1.5/30 was given daily on days 1-21 and serial PK were done on days 10 and 21 and serum progesterone was done on days 11, 15 and 21. In cycle 4 (Treatment D), Loestrin 1.5/30 was given on days 1-11, Loestrin 1.5/30 was given with fostemsavir 600 mg BID on days 12-21. Serial PK was done on day 21 and serum progesterone was measured on day 11, 15, and 21.

Study Results

Only comparisons of EE and NE PK between Treatment D and Treatment C are presented. Fostemsavir coadministration increased EE exposures ~40%. The 90% CIs for NE Cmax and AUC(TAU) GMRs were within 0.80-1.25. Serum progesterone levels suggested fostemsavir did not negatively impact suppression of ovulation. Most study drug-related AEs were mild; 1 subject (3.8%) reported a moderate AE of headache (Treatment D). The EE Cmax (Adjusted Geometric Mean) on day 21 of treatment C was 108 pg/mL and on day 21 of treatment D was 150 pg/mL. The GMR of Treatment D versus Treatment C was 1.39 (1.28, 1.51). The EE AUC tau (Adjusted Geometric Mean) on day 21 of treatment C was 1083 pg/mL and on day 21 of treatment D was 1514. The GMR of Treatment D versus Treatment C was 1.4 (1.29, 1.51). The NE Cmax (Adjusted Geomentric Mean) on day 21 of treatment C was 23629 pg/mL and on day 21 of treatment D was 25582 pg/mL. The GMR of Treatment D versus Treatment C was 1.08 (1.01, 1.16). The NE AUC tau (Adjusted Geometric Mean) on day 21 of treatment C was 170293 pg/mL and on day 21 of treatment D was 184304 pg/mL. The GMR of Treatment D versus Treatment C was 1.08 (1.03, 1.14).

Study Conclusions

Fostemsavir, in the absence of a pharmacoenhancer, may be coadministered with combined oral contraceptives containing NE and a reduced dose of EE.

References

Magee M, Sevinsky H, Ackerman P, Adamczyk R, Griffies A, Myers E. The effect of fostemsavir on pharmacokinetics of a combined oral contraceptive (oc) containing ethinyl estradiol (ee) and norethindrone (ne) in healthy female subjects. International Aids Conference On Hiv Science. Paris, France. 9; July 2017.