Fostemsavir and ethinyl estradiol drug interaction: Clinical recommendations for co‐administration.

Objectives: Fostemsavir, a prodrug of temsavir, is indicated for heavily treatment‐experienced adults with multidrug‐resistant HIV‐1 infection, antiretroviral (ARV) intolerance, or safety considerations. Understanding drug–drug interactions (DDIs) is important in individuals taking fostemsavir with hormonal contraceptives or menopausal or gender‐affirming hormonal therapies. Methods: Effect of temsavir (active moiety) on the pharmacokinetics of ethinyl estradiol (EE) and norethindrone (NET) was evaluated in an open‐label, single‐sequence, four‐cycle, four‐treatment study in 26 healthy female participants (study 206279, NCT02480881). Relevant ARV–contraceptive interaction studies and guideline recommendations were reviewed; that information was then applied to other contraceptive methods and hormone‐based therapies to predict the impact of fostemsavir co‐administration. Results: Temsavir increased EE concentrations by 40% and had no effect on NET concentrations. Fostemsavir co‐administration with hormone therapy is not expected to impact hormone treatment efficacy. Fostemsavir did not impact progestin; therefore, progestin‐only and non‐hormonal contraceptives will not be impacted by fostemsavir. Recommendations for co‐administration of fostemsavir and hormonal contraceptives or menopausal or gender‐affirming hormone therapies are based upon known and predicted DDIs, ensuring adequate hormonal concentrations to maintain the target effect. Conclusions: Applying the results of Study 206279 and other relevant ARV–contraceptive studies, we recommend that when co‐administering fostemsavir with combined oral contraceptives (COCs) and other oestrogen‐based therapies, EE dose should not exceed 30 μg or equivalent, and caution is advised in the case of individuals with risk factors for thromboembolic events. Other oestrogen‐based therapies may be co‐administered with fostemsavir, with monitoring of oestrogen concentrations and appropriate dose adjustments. No impact of fostemsavir on COC efficacy is expected. [ABSTRACT FROM AUTHOR]