Drospirenone/estetrol

{{Infobox drug

| type = combo

| component1 = Drospirenone

| class1 = Progestogen

| component2 = Estetrol (medication)

| class2 = Estrogen

| tradename = Nextstellis, Drovelis, Lydisilka, others

| Drugs.com = {{drugs.com|monograph|estrogen-progestin-combinations}}

| MedlinePlus =

| DailyMedID = Drospirenone_and_estetrol

| pregnancy_AU = B3

| pregnancy_category =

| routes_of_administration = By mouth

| ATC_prefix = G03

| ATC_suffix = AA18

| ATC_supplemental =

| legal_AU = S4

| legal_AU_comment = {{cite web | title=Nextstellis | website=Therapeutic Goods Administration (TGA) | date=6 December 2021 | url=https://www.tga.gov.au/apm-summary/nextstellis | access-date=28 December 2021 | archive-date=28 December 2021 | archive-url=https://web.archive.org/web/20211228081222/https://www.tga.gov.au/apm-summary/nextstellis | url-status=live }}

| legal_BR =

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = {{cite web |title=PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION NEXTSTELLIS |url=https://pdf.hres.ca/dpd_pm/00060352.PDF |access-date=4 July 2024 |date=March 5, 2021 |archive-date=9 July 2022 |archive-url=https://web.archive.org/web/20220709123514/https://pdf.hres.ca/dpd_pm/00060352.PDF |url-status=live }}{{cite web | title=Summary Basis of Decision (SBD) for Nextstellis | website=Health Canada | date=23 October 2014 | url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00536&lang=en | access-date=29 May 2022 | archive-date=30 May 2022 | archive-url=https://web.archive.org/web/20220530041940/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00536&lang=en | url-status=live }}{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=Health Canada | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024 | archive-date=25 March 2024 | archive-url=https://web.archive.org/web/20240325234307/https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | url-status=live }}

| legal_DE =

| legal_DE_comment =

| legal_NZ =

| legal_NZ_comment =

| legal_UK =

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = {{cite web | title=Nextstellis- drospirenone and estetrol kit | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5270073-d083-4109-ae4b-156986175e0a | access-date=1 June 2021 | archive-date=2 June 2021 | archive-url=https://web.archive.org/web/20210602215754/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c5270073-d083-4109-ae4b-156986175e0a | url-status=live }}

| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Drovelis Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1547.htm | access-date=3 March 2023 | archive-date=5 March 2023 | archive-url=https://web.archive.org/web/20230305042410/https://ec.europa.eu/health/documents/community-register/html/h1547.htm | url-status=live }}{{cite web | title=Lydisilka Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1548.htm | access-date=3 March 2023 | archive-date=5 March 2023 | archive-url=https://web.archive.org/web/20230305042256/https://ec.europa.eu/health/documents/community-register/html/h1548.htm | url-status=live }}

| legal_UN =

| legal_UN_comment =

| legal_status =

| CAS_number =

| CAS_supplemental =

| PubChem =

| PubChemSubstance =

| IUPHAR_ligand =

| DrugBank =

| ChemSpiderID = None

| UNII =

| KEGG = D12047

| ChEBI =

| ChEMBL =

| synonyms = E4/DRSP; FSN-013

}}

Drospirenone/estetrol, sold under the brand name Nextstellis, among others, is a fixed-dose combination medication containing drospirenone, a progestin, and estetrol, an estrogen, which is used as a combined birth control pill for the prevention of pregnancy in women. It is taken by mouth.

It was approved for medical use in Canada in March 2021, and in the United States in April 2021.

Medical uses

Drospirenone/estetrol is used as a combined birth control pill to prevent pregnancy in women.

Side effects

Estetrol-containing birth control pills, similarly to estradiol-containing birth control pills, may have a lower risk of venous thromboembolism (VTE) than ethinylestradiol-containing birth control pills based on studies of coagulation.{{cite journal | vauthors = Morimont L, Haguet H, Dogné JM, Gaspard U, Douxfils J | title = Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk | journal = Front Endocrinol (Lausanne) | volume = 12 | issue = | pages = 769187 | date = 2021 | pmid = 34956081 | pmc = 8697849 | doi = 10.3389/fendo.2021.769187 | url = | doi-access = free }}{{cite journal | vauthors = Douxfils J, Morimont L, Bouvy C | title = Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk | journal = Semin Thromb Hemost | volume = 46 | issue = 8 | pages = 872–886 | date = November 2020 | pmid = 33080636 | doi = 10.1055/s-0040-1714140 | s2cid = 224821517 | url = }} However, it is likely that another decade will be required before post-marketing epidemiological studies of VTE incidence with these birth control pills are completed and able to confirm this.{{cite journal | vauthors = Grandi G, Facchinetti F, Bitzer J | title = Confirmation of the safety of combined oral contraceptives containing oestradiol on the risk of venous thromboembolism | journal = Eur J Contracept Reprod Health Care | volume = 27| issue = 2| pages = 83–84 | date = February 2022 | pmid = 35133236 | doi = 10.1080/13625187.2022.2029397 | s2cid = 246651102 | url = | quote = Moreover, the introduction of other new natural oestrogenic components, such as estetrol (E4) [12], could have a similar lower VTE impact; however, we will likely need another decade to obtain results from post-marketing studies.| doi-access = free }}

Pharmacology

=Pharmacodynamics=

Drospirenone/estetrol has a much lower impact on liver protein synthesis, including of sex hormone-binding globulin, angiotensinogen, and coagulation factors, than does ethinylestradiol/drospirenone.{{cite journal | vauthors = Farris M, Bastianelli C, Rosato E, Brosens I, Benagiano G | title = Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis | journal = Expert Rev Clin Pharmacol | volume = 10 | issue = 10 | pages = 1129–1144 | date = October 2017 | pmid = 28712325 | doi = 10.1080/17512433.2017.1356718 | s2cid = 205931204 }}

Society and culture

=Legal status=

Drospirenone/estetrol is approved for the use of hormonal contraception in the European Union,{{Cite web|title=Drovelis EPAR|url=https://www.ema.europa.eu/en/medicines/human/EPAR/drovelis|access-date=4 November 2021|website=European Medicines Agency (EMA)|date=24 March 2021|archive-date=4 November 2021|archive-url=https://web.archive.org/web/20211104153415/https://www.ema.europa.eu/en/medicines/human/EPAR/drovelis|url-status=live}}{{Cite web |title=Lydisilka EPAR |url=https://www.ema.europa.eu/en/medicines/human/EPAR/lydisilka |access-date=4 November 2021 |website=European Medicines Agency (EMA) |date=24 March 2021 |archive-date=4 November 2021 |archive-url=https://web.archive.org/web/20211104153415/https://www.ema.europa.eu/en/medicines/human/EPAR/lydisilka |url-status=live }} the United States,{{cite web | title=Drug Approval Package: Nextstellis | website=U.S. Food & Drug Administration (FDA) | date=12 May 2021 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214154Orig1s000TOC.cfm | access-date=30 November 2021 | archive-date=6 November 2021 | archive-url=https://web.archive.org/web/20211106140547/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2021/214154Orig1s000TOC.cfm | url-status=live }} and Canada.{{Cite web |title=Nextstellis Product information |url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=100241 |access-date=4 November 2021 |website=Health Canada |date=25 April 2012 |archive-date=22 September 2021 |archive-url=https://web.archive.org/web/20210922142740/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=100241 |url-status=live }}

=Brand names=

Drospirenone/estetrol in sold under the brand names Nexstellis, Drovelis, and Lydisilka.

References

External links

{{ClinicalTrialsGov|NCT02817828|E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - EU/Russia Study}}
{{ClinicalTrialsGov|NCT02817841|E4 FREEDOM (Female Response Concerning Efficacy and Safety of Estetrol/Drospirenone as Oral Contraceptive in a Multicentric Study) - United States/Canada Study}}

{{Navboxes

| title = Medical uses

| titlestyle = background:#ccccff

| list1 =

}}