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

Nneka Nwokolo, Elana Post, A Savannah Mageau, Rimi Shah, Mindy Magee, Frank Mannino, Peter Ackerman, Andrew Clark, Katy Moore

HIV medicine 2023 May

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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. 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. 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. 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. © 2022 ViiV Healthcare. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Citation

Nneka Nwokolo, Elana Post, A Savannah Mageau, Rimi Shah, Mindy Magee, Frank Mannino, Peter Ackerman, Andrew Clark, Katy Moore. Fostemsavir and ethinyl estradiol drug interaction: Clinical recommendations for co-administration. HIV medicine. 2023 May;24(5):580-587