Peringatan Keamanan

LD50 information for estetrol is not readily available in the literature. Subjects receiving a dose of 20 mg, 40 mg or 60 mg of estetrol per day over 12 weeks were tolerated without dose-limiting toxicity.A233719 Symptoms that may occur in association with overdose, based on existing information on overdosage with oral contraceptives include nausea, vomiting, and vaginal bleeding. In one clinical study, 1 of 32 healthy research subjects receiving a dose of 75 mg of estretol with 15 mg of drospirenone for 10 days experienced deep vein thrombosis of the lower right limb. There is no known antidote to an estretol overdose; conduct laboratory testing for electrolytes and evidence of metabolic acidosis and provide symptomatic treatment.L33199

Estetrol

DB12235

small molecule approved investigational

Deskripsi

Naturally or synthetically produced steroid estrogens have a wide range of pharmaceutical uses ranging from hormonal contraception to the treatment of menopausal symptoms.L33184 Estetrol (E4) is a native estrogen occurring naturally during pregnancy, but can be synthesized from a plant source and used for contraception.L33179 It is more potent and is safer than the synthetic estrogen ethinylestradiol (EE2) found in 97% of oral contraceptive pills, reducing the environmental accumulation of unwanted endocrine disrupting chemicals (EDCs) that often lead to harmful epigenetic effects.L33184

On April 15 2021, Mayne Pharma Group Limited and Mithra Pharmaceuticals were granted FDA approval for the oral contraceptive Estelle/Nextstellis, a combination of drospirenone and estetrol. Estetrol is the first new estrogen introduced to the USA in over 50 years and is the first approved estetrol product in the world. The combination of drospirenone and estetrol offers a new choice with a favourable safety profile for women seeking contraceptive therapy.L33179 In Canada, Nextstellis was approved for use in March 2021; it was developed by Mithra and is marketed by Searchlight Pharma.L33209

Struktur Molekul 2D

Berat 304.3808
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The elimination half-life of estetrol is approximately 27 hours.[L33174] Half-life may range between 19-40 hours.[A233679]
Volume Distribusi Limited distribution of estetrol into red blood cells has been demonstrated.[L33199]
Klirens (Clearance) -

Absorpsi

Estetrol is rapidly absorbed from the gastrointestinal tract. The Cmax of estetrol is 18 ng/mL according to the results of a pharmacokinetic study, with an AUC of 36.4 ng•h/mL. When estetrol and drospirenone are taken in a single product, maximum serum concentrations of approximately 48.7 ng/mL are achieved within 1-3 h. Bioavailability of the combination ranges between 76 and 85%.L33199 The Tmax can range from 0.5 to 2 hours and time to steady state is approximately 4 days, according to the results of one clinical study.L33174

Metabolisme

Estretol is heavily metabolized after oral administration.L33199 Phase 2 metabolism of estrogen forms glucuronide and sulfate conjugates with negligible in-vitro estrogenic activity. In vitro metabolism studies demonstrate that UGT2B7 catalyzes the formation of E4-16-glucuronide. Estetrol is combined with drospirenone in a product. The hepatic cytochrome enzyme CYP3A4 metabolizes drospirenone to two primary metabolites: the acid form of drospirenone through the opening of the lactone ring and the 4,5­ dihydrodrospirenone formed by reduction, followed by sulfation. Both metabolites are pharmacologically inactive.L33174,L33199

Rute Eliminasi

Estrogens are generally excreted as sulfated and glucuronidated derivatives.A35839 Approximately 69% of a dose of estetrol is excreted in the urine, and about 22% is excreted in the feces as unchanged drug.L33174

Interaksi Makanan

1 Data
  • 1. Take with or without food. Take at the same time each day.

Interaksi Obat

1704 Data
Prucalopride The serum concentration of Estetrol can be decreased when it is combined with Prucalopride.
Prasterone The risk or severity of adverse effects can be increased when Prasterone is combined with Estetrol.
Exemestane The therapeutic efficacy of Exemestane can be decreased when used in combination with Estetrol.
Hyaluronidase (ovine) The therapeutic efficacy of Hyaluronidase (ovine) can be decreased when used in combination with Estetrol.
Hyaluronidase (human recombinant) The therapeutic efficacy of Hyaluronidase (human recombinant) can be decreased when used in combination with Estetrol.
Hyaluronidase The therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Estetrol.
Lenalidomide Estetrol may increase the thrombogenic activities of Lenalidomide.
Ospemifene The risk or severity of adverse effects can be increased when Estetrol is combined with Ospemifene.
Ropinirole Estetrol may increase the excretion rate of Ropinirole which could result in a lower serum level and potentially a reduction in efficacy.
Ursodeoxycholic acid The therapeutic efficacy of Ursodeoxycholic acid can be decreased when used in combination with Estetrol.
Glycochenodeoxycholic Acid The therapeutic efficacy of Glycochenodeoxycholic Acid can be decreased when used in combination with Estetrol.
Cholic Acid The therapeutic efficacy of Cholic Acid can be decreased when used in combination with Estetrol.
Glycocholic acid The therapeutic efficacy of Glycocholic acid can be decreased when used in combination with Estetrol.
Deoxycholic acid The therapeutic efficacy of Deoxycholic acid can be decreased when used in combination with Estetrol.
Taurocholic acid The therapeutic efficacy of Taurocholic acid can be decreased when used in combination with Estetrol.
Obeticholic acid The therapeutic efficacy of Obeticholic acid can be decreased when used in combination with Estetrol.
Chenodeoxycholic acid The therapeutic efficacy of Chenodeoxycholic acid can be decreased when used in combination with Estetrol.
Taurochenodeoxycholic acid The therapeutic efficacy of Taurochenodeoxycholic acid can be decreased when used in combination with Estetrol.
Tauroursodeoxycholic acid The therapeutic efficacy of Tauroursodeoxycholic acid can be decreased when used in combination with Estetrol.
Bamet-UD2 The therapeutic efficacy of Bamet-UD2 can be decreased when used in combination with Estetrol.
cis-Diamminechlorocholylglycinateplatinum(II) The therapeutic efficacy of cis-Diamminechlorocholylglycinateplatinum(II) can be decreased when used in combination with Estetrol.
Dehydrocholic acid The therapeutic efficacy of Dehydrocholic acid can be decreased when used in combination with Estetrol.
Hyodeoxycholic Acid The therapeutic efficacy of Hyodeoxycholic Acid can be decreased when used in combination with Estetrol.
Aramchol The therapeutic efficacy of Aramchol can be decreased when used in combination with Estetrol.
Ox bile extract The therapeutic efficacy of Ox bile extract can be decreased when used in combination with Estetrol.
Cetuximab Estetrol may increase the thrombogenic activities of Cetuximab.
Human immunoglobulin G Estetrol may increase the thrombogenic activities of Human immunoglobulin G.
Omalizumab Estetrol may increase the thrombogenic activities of Omalizumab.
Gemtuzumab ozogamicin Estetrol may increase the thrombogenic activities of Gemtuzumab ozogamicin.
Indium In-111 satumomab pendetide Estetrol may increase the thrombogenic activities of Indium In-111 satumomab pendetide.
Trastuzumab Estetrol may increase the thrombogenic activities of Trastuzumab.
Rituximab Estetrol may increase the thrombogenic activities of Rituximab.
Basiliximab Estetrol may increase the thrombogenic activities of Basiliximab.
Muromonab Estetrol may increase the thrombogenic activities of Muromonab.
Digoxin Immune Fab (Ovine) Estetrol may increase the thrombogenic activities of Digoxin Immune Fab (Ovine).
Ibritumomab tiuxetan Estetrol may increase the thrombogenic activities of Ibritumomab tiuxetan.
Tositumomab Estetrol may increase the thrombogenic activities of Tositumomab.
Alemtuzumab Estetrol may increase the thrombogenic activities of Alemtuzumab.
Capromab pendetide Estetrol may increase the thrombogenic activities of Capromab pendetide.
Efalizumab Estetrol may increase the thrombogenic activities of Efalizumab.
Antithymocyte immunoglobulin (rabbit) Estetrol may increase the thrombogenic activities of Antithymocyte immunoglobulin (rabbit).
Natalizumab Estetrol may increase the thrombogenic activities of Natalizumab.
Palivizumab Estetrol may increase the thrombogenic activities of Palivizumab.
Daclizumab Estetrol may increase the thrombogenic activities of Daclizumab.
Bevacizumab Estetrol may increase the thrombogenic activities of Bevacizumab.
Technetium Tc-99m arcitumomab Estetrol may increase the thrombogenic activities of Technetium Tc-99m arcitumomab.
Eculizumab Estetrol may increase the thrombogenic activities of Eculizumab.
Panitumumab Estetrol may increase the thrombogenic activities of Panitumumab.
Ranibizumab Estetrol may increase the thrombogenic activities of Ranibizumab.
Galiximab Estetrol may increase the thrombogenic activities of Galiximab.
Pexelizumab Estetrol may increase the thrombogenic activities of Pexelizumab.
Epratuzumab Estetrol may increase the thrombogenic activities of Epratuzumab.
Bectumomab Estetrol may increase the thrombogenic activities of Bectumomab.
Oregovomab Estetrol may increase the thrombogenic activities of Oregovomab.
IGN311 Estetrol may increase the thrombogenic activities of IGN311.
Adecatumumab Estetrol may increase the thrombogenic activities of Adecatumumab.
Labetuzumab Estetrol may increase the thrombogenic activities of Labetuzumab.
Matuzumab Estetrol may increase the thrombogenic activities of Matuzumab.
Fontolizumab Estetrol may increase the thrombogenic activities of Fontolizumab.
Bavituximab Estetrol may increase the thrombogenic activities of Bavituximab.
CR002 Estetrol may increase the thrombogenic activities of CR002.
Rozrolimupab Estetrol may increase the thrombogenic activities of Rozrolimupab.
Hepatitis B immune globulin Estetrol may increase the thrombogenic activities of Hepatitis B immune globulin.
Girentuximab Estetrol may increase the thrombogenic activities of Girentuximab.
Obiltoxaximab Estetrol may increase the thrombogenic activities of Obiltoxaximab.
XTL-001 Estetrol may increase the thrombogenic activities of XTL-001.
NAV 1800 Estetrol may increase the thrombogenic activities of NAV 1800.
Briakinumab Estetrol may increase the thrombogenic activities of Briakinumab.
Otelixizumab Estetrol may increase the thrombogenic activities of Otelixizumab.
AMG 108 Estetrol may increase the thrombogenic activities of AMG 108.
Iratumumab Estetrol may increase the thrombogenic activities of Iratumumab.
Enokizumab Estetrol may increase the thrombogenic activities of Enokizumab.
Ramucirumab Estetrol may increase the thrombogenic activities of Ramucirumab.
Farletuzumab Estetrol may increase the thrombogenic activities of Farletuzumab.
Veltuzumab Estetrol may increase the thrombogenic activities of Veltuzumab.
Ustekinumab Estetrol may increase the thrombogenic activities of Ustekinumab.
PRO-542 Estetrol may increase the thrombogenic activities of PRO-542.
TNX-901 Estetrol may increase the thrombogenic activities of TNX-901.
Inotuzumab ozogamicin Estetrol may increase the thrombogenic activities of Inotuzumab ozogamicin.
RI 624 Estetrol may increase the thrombogenic activities of RI 624.
Stamulumab Estetrol may increase the thrombogenic activities of MYO-029.
CT-011 Estetrol may increase the thrombogenic activities of CT-011.
Leronlimab Estetrol may increase the thrombogenic activities of Leronlimab.
Glembatumumab vedotin Estetrol may increase the thrombogenic activities of Glembatumumab vedotin.
Olaratumab Estetrol may increase the thrombogenic activities of Olaratumab.
IPH 2101 Estetrol may increase the thrombogenic activities of IPH 2101.
TB-402 Estetrol may increase the thrombogenic activities of TB-402.
Caplacizumab Estetrol may increase the thrombogenic activities of Caplacizumab.
IMC-1C11 Estetrol may increase the thrombogenic activities of IMC-1C11.
Eldelumab Estetrol may increase the thrombogenic activities of Eldelumab.
Lumiliximab Estetrol may increase the thrombogenic activities of Lumiliximab.
Ipilimumab Estetrol may increase the thrombogenic activities of Ipilimumab.
Nimotuzumab Estetrol may increase the thrombogenic activities of Nimotuzumab.
Clenoliximab Estetrol may increase the thrombogenic activities of Clenoliximab.
BIIB015 Estetrol may increase the thrombogenic activities of BIIB015.
Sonepcizumab Estetrol may increase the thrombogenic activities of Sonepcizumab.
Motavizumab Estetrol may increase the thrombogenic activities of Motavizumab.
Elotuzumab Estetrol may increase the thrombogenic activities of Elotuzumab.
Carotuximab Estetrol may increase the thrombogenic activities of Carotuximab.
XmAb 2513 Estetrol may increase the thrombogenic activities of XmAb 2513.

Target Protein

Estrogen receptor ESR1
Estrogen receptor beta ESR2

Referensi & Sumber

Synthesis reference: Johannes Jan Platteeuw, Herman Jan Tijmen, Coelingh Bennink, Franciscus Wilhelmus, Petrus Damen, Michiel Christian, Alexander Van Vliet. (2013).Process for the preparation of estetrol. (WO2013012328A1).https://patents.google.com/patent/WO2013012328A1/en18
Artikel (PubMed)
  • PMID: 28641030
    Apter D, Zimmerman Y, Beekman L, Mawet M, Maillard C, Foidart JM, Coelingh Bennink HJT: Estetrol combined with drospirenone: an oral contraceptive with high acceptability, user satisfaction, well-being and favourable body weight control. Eur J Contracept Reprod Health Care. 2017 Aug;22(4):260-267. doi: 10.1080/13625187.2017.1336532. Epub 2017 Jun 22.
  • PMID: 26257704
    Montt-Guevara MM, Giretti MS, Russo E, Giannini A, Mannella P, Genazzani AR, Genazzani AD, Simoncini T: Estetrol Modulates Endothelial Nitric Oxide Synthesis in Human Endothelial Cells. Front Endocrinol (Lausanne). 2015 Jul 22;6:111. doi: 10.3389/fendo.2015.00111. eCollection 2015.
  • PMID: 32379217
    Gaspard U, Taziaux M, Mawet M, Jost M, Gordenne V, Coelingh Bennink HJT, Lobo RA, Utian WH, Foidart JM: A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety. Menopause. 2020 Aug;27(8):848-857. doi: 10.1097/GME.0000000000001561.
  • PMID: 25214462
    Abot A, Fontaine C, Buscato M, Solinhac R, Flouriot G, Fabre A, Drougard A, Rajan S, Laine M, Milon A, Muller I, Henrion D, Adlanmerini M, Valera MC, Gompel A, Gerard C, Pequeux C, Mestdagt M, Raymond-Letron I, Knauf C, Ferriere F, Valet P, Gourdy P, Katzenellenbogen BS, Katzenellenbogen JA, Lenfant F, Greene GL, Foidart JM, Arnal JF: The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor alpha modulation, uncoupling nuclear and membrane activation. EMBO Mol Med. 2014 Oct;6(10):1328-46. doi: 10.15252/emmm.201404112.
  • PMID: 32238069
    Grandi G, Del Savio MC, Lopes da Silva-Filho A, Facchinetti F: Estetrol (E4): the new estrogenic component of combined oral contraceptives. Expert Rev Clin Pharmacol. 2020 Apr;13(4):327-330. doi: 10.1080/17512433.2020.1750365. Epub 2020 Apr 7.
  • PMID: 28267365
    Coelingh Bennink HJT, Verhoeven C, Zimmerman Y, Visser M, Foidart JM, Gemzell-Danielsson K: Pharmacokinetics of the fetal estrogen estetrol in a multiple-rising-dose study in postmenopausal women. Climacteric. 2017 Jun;20(3):285-289. doi: 10.1080/13697137.2017.1291608. Epub 2017 Mar 7.
  • PMID: 18464021
    Visser M, Holinka CF, Coelingh Bennink HJ: First human exposure to exogenous single-dose oral estetrol in early postmenopausal women. Climacteric. 2008;11 Suppl 1:31-40. doi: 10.1080/13697130802056511.
  • PMID: 18464025
    Visser M, Foidart JM, Coelingh Bennink HJ: In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism. Climacteric. 2008;11 Suppl 1:64-8. doi: 10.1080/13697130802050340.
Menampilkan 8 dari 12 artikel.

Contoh Produk & Brand

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International Brands
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Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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