Relugolix/estradiol/norethisterone acetate

{{Short description|Combination medication}} {{Use dmy dates|date=February 2024}} {{cs1 config | name-list-style=vanc | display-authors=6}} {{Infobox drug | type = combo | image = Relugolix, estradiol and norethisterone acetate.svg | image_class = skin-invert-image | alt =

| tradename = Myfembree, Ryeqo | Drugs.com = {{drugs.com|mtm|estradiol-norethindrone-and-relugolix}} | MedlinePlus = a622069 | DailyMedID = Relugolix and estradiol | pregnancy_AU = D | pregnancy_AU_comment = <ref>{{Cite web |url=http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2022-PI-01955-1 |title=TGA eBS - Product and Consumer Medicine Information Licence |access-date=18 March 2023 |archive-date=18 March 2023 |archive-url=https://web.archive.org/web/20230318060222/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent=&id=CP-2022-PI-01955-1 |url-status=live }}</ref> | pregnancy_category = | routes_of_administration = By mouth | ATC_prefix = H01 | ATC_suffix = CC54 | ATC_supplemental =

| legal_AU = S4 | legal_AU_comment = <ref>{{cite web | title=Ryeqo (Gedeon Richter Australia Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=7 October 2022 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/ryeqo-gedeon-richter-australia-pty-ltd | access-date=29 April 2023 | archive-date=18 March 2023 | archive-url=https://web.archive.org/web/20230318054645/https://www.tga.gov.au/resources/prescription-medicines-registrations/ryeqo-gedeon-richter-australia-pty-ltd | url-status=live }}</ref><ref>{{cite web | title=Ryeqo 40/1/0.5 relugolix 40 mg/estradiol 1 mg/norethisterone acetate 0.5 mg film coated tablet bottle (375414) | website=Therapeutic Goods Administration (TGA) | date=7 September 2022 | url=https://www.tga.gov.au/resources/artg/375414 | access-date=8 March 2024}}</ref> | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Details for: Myfembree | website=Health Canada | date=29 January 2024 | url=https://dhpp.hpfb-dgpsa.ca/dhpp/resource/103029 | access-date=3 March 2024}}</ref><ref>{{cite web | title=Regulatory Decision Summary for Myfembree | website=Drug and Health Products Portal | date=22 September 2023 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS1710259036712 | access-date=2 April 2024}}</ref><ref>{{cite web | title=Summary Basis of Decision (SBD) for Myfembree | website=Drug and Health Products Portal | date=1 September 2012 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1712172719912 | access-date=9 May 2024}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK = POM | legal_UK_comment = <ref name="Ryeqo SmPC">{{cite web | title=Ryeqo 40mg/1mg/0.5mg film-coated tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=12 September 2022 | url=https://www.medicines.org.uk/emc/product/12934/smpc | access-date=17 March 2023 | archive-date=18 March 2023 | archive-url=https://web.archive.org/web/20230318060218/https://www.medicines.org.uk/emc/product/12934/smpc | url-status=live }}</ref> | legal_US = Rx-only | legal_US_comment = <ref name="Myfembree FDA label">{{cite web | title=Myfembree- relugolix, estradiol hemihydrate, and norethindrone acetate tablet, film coated | website=DailyMed | date=2 February 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc3feb73-cc84-43a8-aa32-b262460495e8 | access-date=11 March 2023 | archive-date=12 March 2023 | archive-url=https://web.archive.org/web/20230312062939/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc3feb73-cc84-43a8-aa32-b262460495e8 | url-status=live }}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Ryeqo EPAR" /> | legal_UN =  | legal_UN_comment = | legal_status =

| CAS_number = | CAS_supplemental = | PubChem = | IUPHAR_ligand = | DrugBank = | ChemSpiderID = | UNII = | KEGG = D12226 | ChEBI = | ChEMBL = | NIAID_ChemDB = | PDB_ligand = | synonyms = RGX/E2/NETA; MVT-601 }}

'''Relugolix/estradiol/norethisterone acetate''', sold under the brand names '''Myfembree''' and '''Ryeqo''', is a fixed-dose combination hormonal medication which is used for the treatment of heavy menstrual bleeding associated with uterine leiomyomas (fibroids) and for moderate to severe pain associated with endometriosis.<ref name="Myfembree FDA label" /><ref name="Ryeqo EPAR" /><ref name="Pfizer2022">{{cite web | title=Myovant Sciences and Pfizer Receive U.S. FDA Approval of Myfembree, a Once-Daily Treatment for the Management of Moderate to Severe Pain Associated With Endometriosis | website=Pfizer | date=8 August 2022 | url=https://www.pfizer.com/news/press-release/press-release-detail/myovant-sciences-and-pfizer-receive-us-fda-approval | access-date=28 August 2022 | archive-date=28 August 2022 | archive-url=https://web.archive.org/web/20220828143028/https://www.pfizer.com/news/press-release/press-release-detail/myovant-sciences-and-pfizer-receive-us-fda-approval | url-status=live }}</ref> It contains relugolix, an orally active gonadotropin-releasing hormone antagonist (GnRH antagonist), estradiol, an estrogen, and norethisterone acetate, a progestin.<ref name="Myfembree FDA label" /><ref name="Ryeqo EPAR" /> The medication is taken by mouth.<ref name="Myfembree FDA label" />

The most common side effects of the medication include hot flushes, excessive sweating or night sweats, uterine bleeding, hair loss or thinning, and decreased interest in sex.<ref name="Myfembree FDA label" />

The medication was approved for medical use in the United States in May 2021,<ref name="Myfembree FDA label" /><ref name="Myfembree">{{cite web | title=Myfembree: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=214846 | access-date=28 August 2022 | archive-date=11 August 2022 | archive-url=https://web.archive.org/web/20220811005135/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=214846 | url-status=dead }}</ref><ref>{{cite press release | title=Myovant Sciences and Pfizer Receive FDA Approval for Myfembree, the First Once-Daily Treatment for Heavy Menstrual Bleeding Associated With Uterine Fibroids | website=Pfizer | date=26 May 2021 | url=https://www.pfizer.com/news/press-release/press-release-detail/myovant-sciences-and-pfizer-receive-fda-approval-myfembreer | access-date=26 May 2021 | archive-date=26 May 2021 | archive-url=https://web.archive.org/web/20210526210118/https://www.pfizer.com/news/press-release/press-release-detail/myovant-sciences-and-pfizer-receive-fda-approval-myfembreer | url-status=live }}</ref> and in the European Union in July 2021.<ref name="Ryeqo EPAR" />

==Medical uses== The medication is used in the treatment of heavy menstrual bleeding associated with uterine fibroids and for moderate to severe pain associated with endometriosis, both in premenopausal women.<ref name="Myfembree FDA label" /><ref name="Pfizer2022" />

===Available forms=== The medication is formulated as an oral tablet containing a fixed-dose combination of 40{{nbsp}}mg relugolix, 1{{nbsp}}mg estradiol, and 0.5{{nbsp}}mg norethisterone acetate.<ref name="Myfembree FDA label" />

==Pharmacology==

===Pharmacodynamics=== Relugolix acts as an GnRH antagonist, or an antagonist of the gonadotropin-releasing hormone receptor.<ref name="pmid35068291">{{cite journal | vauthors = Ali M, Chen HY, Chiang YF, Badary OA, Hsia SM, Al-Hendy A | title = An evaluation of relugolix/estradiol/norethindrone acetate for the treatment of heavy menstrual bleeding associated with uterine fibroids in premenopausal women | journal = Expert Opin Pharmacother | volume = 23 | issue = 4 | pages = 421–429 | date = March 2022 | pmid = 35068291 | doi = 10.1080/14656566.2022.2030705 | pmc = 8866208 | url = }}</ref> Estradiol is an estrogen, or an agonist of the estrogen receptors, whereas norethisterone acetate is a progestin (synthetic progestogen), or an agonist of the progesterone receptors.<ref name="pmid16112947">{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | issue = Suppl 1| pages = 3–63 | date = August 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = }}</ref> Relugolix suppresses ovarian sex hormone production, whereas estradiol and norethisterone acetate provide hormonal add-back to reduce hypogonadal and menopausal-like symptoms.<ref name="pmid35068291" />

==History== The medication was approved for medical use in the United States in May 2021.<ref name="Myfembree FDA label" /><ref name="Myfembree" />

In May 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Ryeqo, intended for the treatment of symptoms of uterine fibroids.<ref name="Ryeqo: Pending EC decision" /> The applicant for this medicinal product is Gedeon Richter Plc.<ref name="Ryeqo: Pending EC decision">{{cite web | title=Ryeqo: Pending EC decision | website=European Medicines Agency (EMA) | date=20 May 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/ryeqo | access-date=25 May 2021 | archive-date=26 May 2021 | archive-url=https://web.archive.org/web/20210526051359/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/ryeqo | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> The combination was approved for medical use in the European Union in July 2021.<ref name="Ryeqo EPAR">{{cite web | title=Ryeqo EPAR | website=European Medicines Agency | date=19 May 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/ryeqo | access-date=24 April 2022 | archive-date=29 April 2022 | archive-url=https://web.archive.org/web/20220429224439/https://www.ema.europa.eu/en/medicines/human/EPAR/ryeqo | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref><ref>{{cite web | title=Ryeqo Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1565.htm | access-date=3 March 2023 | archive-date=4 March 2023 | archive-url=https://web.archive.org/web/20230304111717/https://ec.europa.eu/health/documents/community-register/html/h1565.htm | url-status=live }}</ref>

In August 2022, the medication was approved for the treatment of moderate to severe pain associated with endometriosis in the United States.<ref name="Pfizer2022" />

==Research== The combination is also under development as a birth control pill for prevention of pregnancy in premenopausal women.<ref name="AdisInsight">{{cite web | title=Estradiol/norethisterone acetate/relugolix - Myovant Sciences | website=AdisInsight | date=22 August 2022 | url=https://adisinsight.springer.com/drugs/800058162 | access-date=28 August 2022 | archive-date=28 August 2022 | archive-url=https://web.archive.org/web/20220828143222/https://adisinsight.springer.com/drugs/800058162 | url-status=live }}</ref>

==References== {{Reflist}}

==Further reading== * {{cite journal |vauthors=Al-Hendy A, Lukes AS, Poindexter AN, Venturella R, Villarroel C, Critchley HO, Li Y, McKain L, Arjona Ferreira JC, Langenberg AG, Wagman RB, Stewart EA |title=Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy |journal=The New England Journal of Medicine |volume=384 |issue=7 |pages=630–42 |date=February 2021 |pmid=33596357 |doi=10.1056/NEJMoa2008283 |pmc=8262231 }}

{{Navboxes | title = Medical uses | titlestyle = background:#ccccff | list1 = {{Pituitary and hypothalamic hormones and analogues}} {{Hormonal contraceptives}} {{Estrogens and antiestrogens}} {{Progestogens and antiprogestogens}} {{GnRH and gonadotropins}} }} {{Navboxes | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 = {{Androgen receptor modulators}} {{Estrogen receptor modulators}} {{GnRH and gonadotropin receptor modulators}} {{Progesterone receptor modulators}} }} {{Portal bar | Medicine}} {{Authority control}}

{{DEFAULTSORT:Relugolix Estradiol Norethisterone Acetate}} Category:Combination sex hormone drugs