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Clinical Pharmacokinetics

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01-01-2021 | Norethisterone | Original Research Article

Drug–Drug Interaction Studies of Elagolix with Oral and Transdermal Low-Dose Hormonal Add-Back Therapy

Authors: Ahmed Nader, Nael M. Mostafa, Farah Ali, Mohamad Shebley

Published in: Clinical Pharmacokinetics | Issue 1/2021

Abstract

Background and Objective

Elagolix is an oral, non-peptide, gonadotropin-releasing hormone receptor antagonist. It is approved for the treatment of moderate-to-severe pain associated with endometriosis and is being investigated for the treatment of heavy menstrual bleeding associated with uterine fibroids. Use of low-dose hormonal add-back therapy can reduce hypoestrogenic effects associated with elagolix, thus there is a need to determine if there is a pharmacokinetic interaction between elagolix and low-dose hormonal add-back therapy.

Methods

Two multiple-dose, open-label, single-sequence, non-randomized studies for elagolix 300 mg twice daily with oral (n = 24) and transdermal (n = 36) low-dose add-back therapy (estradiol [E2]/norethindrone acetate [NETA]; 1 mg/0.5 mg oral and 0.51 mg/4.8 mg transdermal) in healthy postmenopausal women were conducted, with pharmacokinetic sampling for E2, estrone (E1), and NETA up to 72 or 96 h after dosing. Pharmacokinetic parameters for hormones were estimated using noncompartmental methods.

Results

No change in norethindrone maximum plasma concentration or area under the concentration–time curve was observed when oral E2/NETA was administered with elagolix. For E2, there was a 2-fold increase in maximum plasma concentration and a 1.5-fold increase in the area under the concentration–time curve, and for E1 there was a 1.7-fold increase in maximum plasma concentration when oral E2/NETA was administered with elagolix. Exposures for norethindrone, E2, and E1 were unchanged when transdermal E2/NETA was applied with elagolix administration.

Conclusions

Although changes in E2/E1 exposures were observed when oral E2/NETA was co-administered with elagolix, these changes are not considered clinically relevant; and no dose adjustments are recommended when elagolix is co-administered with oral or transdermal low-dose add-back therapy.

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Title: Drug–Drug Interaction Studies of Elagolix with Oral and Transdermal Low-Dose Hormonal Add-Back Therapy
Authors: Ahmed Nader
Nael M. Mostafa
Farah Ali
Mohamad Shebley
Publication date: 01-01-2021
Publisher: Springer International Publishing
Keywords: Norethisterone
Estradiol
Published in: Clinical Pharmacokinetics / Issue 1/2021
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-020-00921-y

At a glance: The STEP trials

Springer Medicine

Drug–Drug Interaction Studies of Elagolix with Oral and Transdermal Low-Dose Hormonal Add-Back Therapy

Abstract

Background and Objective

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background and Objective

Methods

Results

Conclusions

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