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Fostemsavir and Ethinyl Estradiol Drug Interaction: Clinical Application for Co-Administration

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Fostemsavir and Ethinyl Estradiol Drug Interaction: Clinical Application for Co-Administration FOSTEMSAVIR AND ETHINYL ESTRADIOL DRUG INTERACTION: CLINICAL APPLICATION FOR CO-ADMINISTRATION Nneka Nwokolo,1 Elana Post,2 Mindy Magee,3 Peter Ackerman,4 Cyril Llamoso,4 Katy Moore2 1ViiV Healthcare, Brentford, UK; 2ViiV Healthcare, Research Triangle Park, NC, USA; 3GlaxoSmithKline, Upper Providence, PA, USA; 4ViiV Healthcare, Branford, CT, USA P102 Introduction Table 2. FTR and Contraceptive Co-administration • Fostemsavir (FTR) is a first-in-class attachment inhibitor indicated for heavily Delivery Data and Guideline Recommendation2 FTR Co-administration treatment-experienced (HTE) people living with human immunodeficiency virus-1 Combined Hormonal Contraceptives (HIV-1) (PLWH) INSTIs INSTIs + FTR + COC: • FTR is a prodrug of temsavir (TMR), which binds viral gp120 and prevents viral • BIC, DTG, RAL: EE ↔, norgestimate ↔; No dose Maintain EE ≤30 μg/day adjustment needed for COC or ARV attachment and entry into host CD4+ T cells Boosted PIs Boosted PIs + FTR + • FTR is used with other antiretrovirals (ARVs) in PLWH who are failing on their • ATV/r: EE AUC 19%, norgestimate AUC 85%; COC: current treatment regimen and who have limited remaining treatment options due Maintain EE ≥35 μg/day Consider alternative to resistance, intolerance, or other safety concerns • ATV/c: EE AUC 22%, drospirenone 2.3-fold; ARV or additional Contraindicated with drospirenone-containing contraceptive methods, Methods products, use alternative ARV or contraceptive guided by PI method prescribing • FTR-Oral Contraceptive (OC) Study with ethinyl estradiol (EE) and norethindrone Combined • DRV/r, LPV/r, TPV/r: EE AUC 37%-55%, recommendations (NE) (Figure 1), relevant ARV-contraceptive interaction studies, and guideline oral NE 14%-34%; Use alternative ARV or recommendations were reviewed, and data applied to other contraceptive methods contra- contraceptive method and hormone-based therapies to predict the impact of FTR co-administration ception NNRTIs NNRTIs + FTR + COC: • Recommendations were based on minimizing risk associated with estrogen (COC) • DOR: EE ↔, levonorgestrel ↔; No dose • DOR, RPV – Maintain exposure (Figure 2) and ensuring adequate hormonal concentrations to maintain adjustment needed for COC or ARV EE ≤30 μg/day targeted effect by anticipating EE concentrations with co-administration of FTR • RPV: EE ↔, NE ↔; No dose adjustment needed • ETR, NVP, EFV – with different estrogen-based therapies and concomitant ARV therapy for COC or ARV Consider alternative • ETR: EE AUC 22%, NE ↔; No dose adjustment ARV or additional • Proposals for co-administering FTR with an ARV regimen with estrogen-based needed for COC or ARV contraceptive therapies (contraception, menopausal hormone therapy [MHT], and feminizing • NVP: EE AUC 29%, NE AUC 18%; No dose methods gender-affirming hormone therapy [GAHT]) are provided adjustment needed for COC or ARV • EFV: EE ↔, levonorgestrel AUC 83%, 1 Figure 1. FTR-OC Study (Study 206279) EE: 40%; No Impact on NE norelgestromin 64%; Use alternative ARV or contraceptive method INSTIs INSTIs + FTR + CHP: • No guideline recommendation available No expected impact Boosted PIs Boosted PIs + FTR + Combined • LPV/r: EE AUC 45%, norelgestromin 83%; CHP: hormonal No dose adjustment needed for CHP or ARV Consider alternative patch • All PIs: no data; No dose adjustment needed ARV or additional (CHP) contraceptive methods NNRTIs • No guideline recommendation available NNRTIs + FTR + CHP: Insufficient data for a recommendation Figure 2. History of Combined Oral Contraception (COC), Estrogen Dose, and Safety INSTIs INSTIs + FTR + CVR: • No guideline recommendation available No expected impact Boosted PIs Boosted PIs + FTR + • ATV/r: EE AUC 26%, etonogestrel AUC 79%; CVR: No dose adjustment needed for CVR or ARV Consider alternative • All PIs: no data; No dose adjustment needed ARV or additional Combined contraceptive methods NNRTIs vaginal NNRTIs + FTR + CVR: ring (CVR) • DOR, RPV: EE ↔, etonogestrel ↔; No dose adjustment needed for CVR or ARV • DOR, RPV – No expected impact • ETR, NVP: EE and etonogestrel possible; No data for recommendation • ETR, NVP, EFV – Insufficient data for • EFV: EE AUC 56%, etonogestrel AUC 81%; a recommendation Consider alternative ARV or contraceptive Results method Table 1. FTR and MHT and GAHT Co-administration Progestin-only Contraceptives Progestin-only implant; DMPA; Progestin-only pill No impact with FTR FTR Co- Barrier Contraceptive Methods Data and Guideline Recommendation2 administration Condoms; Spermicides; Diaphragm with spermicide or cervical cap No impact with FTR Menopausal Hormone Therapy (MHT) INSTIs Start estrogen • BIC, DTG, RAL: ↔ estrogen expected with estradiol or conjugated dose low and Conclusions estrogen – No dose adjustment needed titrate according FTR co-administration with hormone therapy is not expected to impact Boosted PIs to clinical effect. • All PIs: or estrogen possible with estradiol or conjugated hormone treatment efficacy estrogen – Adjust estrogen dose as needed based on clinical effects Contraception NNRTIs • When FTR is co-administered with oral estrogen-based therapies, EE • DOR, RPV: ↔ hormonal concentrations – No dose adjustment dose should be ≤30 μg/day to minimize risk needed • FTR did not impact progestin. Therefore, progestin-only and non- • EFV, ETR, NVP: estrogen possible with estradiol or conjugated hormonal contraceptives will not be impacted by FTR estrogen – Monitor menopausal symptoms. Titrate to the dose of 2 hormonal therapy that achieves menopausal symptom relief • When FTR, ARVs, and COC are co-administered, reference guidelines Feminizing Gender-Affirming Hormone Therapy (GAHT) MHT and GAHT • Estrogen-containing MHT and GAHT can be co-administered with FTR, INSTIs FTR and estradiol with monitoring of estrogen concentrations and dose adjustment as • BIC, DTG, RAL: ↔ estrogen expected – No dose adjustment for GAHT can be needed needed co-administered With MHT, starting EE low and titrating according to clinical effect will enable Boosted PIs with routine • monitoring of prescription of the lowest effective dose of estrogen • PI/r: estradiol possible – Adjust estradiol dose as needed based hormone on clinical effects and endogenous hormone concentrations • Feminizing GAHT regimens target serum estradiol concentrations in the concentrations physiologic cisgender female range of 100 to 200 pg/mL. Routine monitoring • PI/c: or estradiol possible – Adjust estradiol dose as needed and clinical of concentrations will allow dose adjustments to achieve goal concentrations based on clinical effects and endogenous hormone concentrations effects, titrating NNRTIs estradiol dose in Abbreviations: INSTI, integrase strand transfer inhibitor; BIC, bictegravir; DTG, dolutegravir; RAL, raltegravir; PI, protease inhibitor; • DOR, RPV: ↔ hormonal concentrations – No dose adjustment line with NNRTI, nonnucleoside reverse transcriptase inhibitor; DOR, doravirine; RPV, rilpivirine; EFV, efavirenz; ETR, etravirine; NVP, nevirapine; needed guidelines. r, ritonavir; c, cobicistat; ATV, atazanavir; DRV, darunavir; LPV, lopinavir; TPV, tipranavir; DMPA, depot medroxyprogesterone acetate. Acknowledgments: This study was funded by ViiV Healthcare. Editorial assistance and graphic design support for this poster were provided • EFV, ETR, NVP: estradiol possible – Monitor feminizing effects of under the direction of the authors by MedThink SciCom and funded by ViiV Healthcare. Data included in this poster have been previously estrogen and antiandrogen therapy and titrate dose as necessary to presented in full at the 10th International Workshop on HIV & Women; March 6-7, 2020; Virtual; Poster 22. References: 1. Magee et al. IAS 2017; Paris, France. Abstract MOPEB0339. 2. AIDSinfo. https://aidsinfo.nih.gov/guidelines/html/1/adult-and- achieve therapeutic goals adolescent-arv/23/women-with-hiv. Accessed January 28, 2020. HIV Drug Therapy Glasgow 2020; October 5-8, 2020; Virtual Presenting author: Nneka Nwokolo; [email protected].
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