Peringatan Keamanan

>2000 mg/kg MSDS

The Million Women Study (MWS), which had a prospective observational design, studied the use of hormone replacement therapy. The results indicated that the increase in the incidence of breast cancer with estrogen and progestogen (compared to estrogen alone) was greater than the reduction in occurrence of endometrial cancer associated with adding progestogen to estrogen therapy. The MWS also reported a marked increase in the incidence of breast cancer with tibolone and with implanted and transdermal estrogen-only preparations L1723.

Tibolone treatment in rodent studies showed an increased association with the development of a range of tumors in long-term oral carcinogenicity studies. These tumors included pituitary adenomas, mammary carcinomas and fibroadenomas, hepatic adenomas, uterine carcinoma, stromal polyps and stromal sarcoma, and carcinomas of the urinary bladder and testes. Tibolone failed to show any evidence of genotoxicity in studies for gene mutations, chromosomal damage as well as DNA damage L1727.

Other adverse effects these include dizziness, headache, nausea, abdominal pain, rashes, pruritus, weight gain, edema, and migraine L1728.

Tibolone

DB09070

small molecule approved investigational

Deskripsi

Tibolone is a synthetic steroid hormone drug, which is mainly non-selective in its binding profile, acting as an agonist primarily at estrogen receptors (ER), with a preference for ER alpha L1874.

Tibolone (Livial, Org OD 14), produced by Organon (West Orange, NJ), is a synthetic steroid that possesses estrogenic, androgenic and progestogenic properties. It has been used in Europe for almost 2 decades, primarily for the prevention of postmenopausal osteoporosis and the treatment of post-menopausal symptoms L1720. Tibolone is approved in 90 countries to manage menopausal symptoms and in 45 countries to prevent the development of osteoporosis L1876.

In June 2006, Organon Pharmaceuticals announced the receipt of a Not Approvable Letter from the U.S. Food and Drug Administration (FDA), advising the company that the New Drug Application (NDA) for tibolone had not been approved L1722.

Interestingly, the use of tibolone in the treatment cardiovascular disease has been studied with inconclusive results A32164. Tibolone has been to have anti-resorptive effects on bone L1874.

Struktur Molekul 2D

Berat 312.453
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 is approximately 45 h [L1720].
Volume Distribusi -
Klirens (Clearance) Elimination of tibolone is not dependent renal function [L1879].

Absorpsi

Tibolone is extensively and rapidly absorbed after oral administration L1879. The parent drug undergoes extensive metabolism, with. Greater than 80% of a radioactive dose excreted from the body as metabolites, which suggests very low plasma concentrations of tibolone. Plasma concentrations of the metabolites appear within 30 minutes and peak within 1–1.5 hours.2,7 The plasma concentrations of the hydroxymetabolites are higher than those of the ?4-isomer. Food does not appear to have an effect on the absorption of this drug L1879.

Metabolisme

Tibolone is metabolized mainly in the liver L1720. The cytochrome P450 isoenzyme system is involved in minor hydroxylation of tibolone L1879. Tibolone is rapidly converted into three major metabolites: 3 alpha- and 3 beta-hydroxy-tibolone, which have oestrogenic effects, and the Delta(4)-isomer, which has both progestogenic and androgenic effects. The 3-hydroxy metabolites are present in the circulation, predominantly in their inactive sulfated form A32150.

Rute Eliminasi

Excreted in the urine and feces in the form of sulfated metabolites.L1720, L1879 About 40% of the drug is excreted as metabolites in urine.L1728 The predominant route of elimination of tibolone is via the feces:L1879 about 60% of the drug is excreted as metabolites in feces.L1728

Interaksi Makanan

2 Data
  • 1. Avoid St. John's Wort. St. John's Wort induces CYP3A4, increasing the metabolism of estrogens and progesterone and therefore reducing the efficacy of tibolone.
  • 2. Take with or without food.

Interaksi Obat

548 Data
Lepirudin Tibolone may increase the anticoagulant activities of Lepirudin.
Bivalirudin Tibolone may increase the anticoagulant activities of Bivalirudin.
Alteplase Tibolone may increase the anticoagulant activities of Alteplase.
Urokinase Tibolone may increase the anticoagulant activities of Urokinase.
Reteplase Tibolone may increase the anticoagulant activities of Reteplase.
Anistreplase Tibolone may increase the anticoagulant activities of Anistreplase.
Tenecteplase Tibolone may increase the anticoagulant activities of Tenecteplase.
Abciximab Tibolone may increase the anticoagulant activities of Abciximab.
Drotrecogin alfa Tibolone may increase the anticoagulant activities of Drotrecogin alfa.
Streptokinase Tibolone may increase the anticoagulant activities of Streptokinase.
Dicoumarol Tibolone may increase the anticoagulant activities of Dicoumarol.
Argatroban Tibolone may increase the anticoagulant activities of Argatroban.
Ardeparin Tibolone may increase the anticoagulant activities of Ardeparin.
Phenindione Tibolone may increase the anticoagulant activities of Phenindione.
Fondaparinux Tibolone may increase the anticoagulant activities of Fondaparinux.
Warfarin Tibolone may increase the anticoagulant activities of Warfarin.
Pentosan polysulfate Tibolone may increase the anticoagulant activities of Pentosan polysulfate.
Phenprocoumon Tibolone may increase the anticoagulant activities of Phenprocoumon.
Dipyridamole Tibolone may increase the anticoagulant activities of Dipyridamole.
Heparin Tibolone may increase the anticoagulant activities of Heparin.
Enoxaparin Tibolone may increase the anticoagulant activities of Enoxaparin.
Epoprostenol Tibolone may increase the anticoagulant activities of Epoprostenol.
Acenocoumarol Tibolone may increase the anticoagulant activities of Acenocoumarol.
4-hydroxycoumarin Tibolone may increase the anticoagulant activities of 4-hydroxycoumarin.
Coumarin Tibolone may increase the anticoagulant activities of Coumarin.
Ximelagatran Tibolone may increase the anticoagulant activities of Ximelagatran.
Desmoteplase Tibolone may increase the anticoagulant activities of Desmoteplase.
Defibrotide Tibolone may increase the anticoagulant activities of Defibrotide.
Ancrod Tibolone may increase the anticoagulant activities of Ancrod.
Beraprost Tibolone may increase the anticoagulant activities of Beraprost.
Prasugrel Tibolone may increase the anticoagulant activities of Prasugrel.
Rivaroxaban Tibolone may increase the anticoagulant activities of Rivaroxaban.
Sulodexide Tibolone may increase the anticoagulant activities of Sulodexide.
Semuloparin Tibolone may increase the anticoagulant activities of Semuloparin.
Idraparinux Tibolone may increase the anticoagulant activities of Idraparinux.
Cangrelor Tibolone may increase the anticoagulant activities of Cangrelor.
Astaxanthin Tibolone may increase the anticoagulant activities of Astaxanthin.
Apixaban Tibolone may increase the anticoagulant activities of Apixaban.
Otamixaban Tibolone may increase the anticoagulant activities of Otamixaban.
Amediplase Tibolone may increase the anticoagulant activities of Amediplase.
Dabigatran etexilate Tibolone may increase the anticoagulant activities of Dabigatran etexilate.
Danaparoid Tibolone may increase the anticoagulant activities of Danaparoid.
Dalteparin Tibolone may increase the anticoagulant activities of Dalteparin.
Tinzaparin Tibolone may increase the anticoagulant activities of Tinzaparin.
(R)-warfarin Tibolone may increase the anticoagulant activities of (R)-warfarin.
Ethyl biscoumacetate Tibolone may increase the anticoagulant activities of Ethyl biscoumacetate.
Nadroparin Tibolone may increase the anticoagulant activities of Nadroparin.
Triflusal Tibolone may increase the anticoagulant activities of Triflusal.
Ticagrelor Tibolone may increase the anticoagulant activities of Ticagrelor.
Ditazole Tibolone may increase the anticoagulant activities of Ditazole.
Vorapaxar Tibolone may increase the anticoagulant activities of Vorapaxar.
Edoxaban Tibolone may increase the anticoagulant activities of Edoxaban.
Sodium citrate Tibolone may increase the anticoagulant activities of Sodium citrate.
Dextran Tibolone may increase the anticoagulant activities of Dextran.
Bemiparin Tibolone may increase the anticoagulant activities of Bemiparin.
Parnaparin Tibolone may increase the anticoagulant activities of Parnaparin.
Desirudin Tibolone may increase the anticoagulant activities of Desirudin.
Antithrombin Alfa Tibolone may increase the anticoagulant activities of Antithrombin Alfa.
Protein C Tibolone may increase the anticoagulant activities of Protein C.
Antithrombin III human Tibolone may increase the anticoagulant activities of Antithrombin III human.
Letaxaban Tibolone may increase the anticoagulant activities of Letaxaban.
Darexaban Tibolone may increase the anticoagulant activities of Darexaban.
Betrixaban Tibolone may increase the anticoagulant activities of Betrixaban.
Nafamostat Tibolone may increase the anticoagulant activities of Nafamostat.
Monteplase Tibolone may increase the anticoagulant activities of Monteplase.
Gabexate Tibolone may increase the anticoagulant activities of Gabexate.
Fluindione Tibolone may increase the anticoagulant activities of Fluindione.
Protein S human Tibolone may increase the anticoagulant activities of Protein S human.
Brinase Tibolone may increase the anticoagulant activities of Brinase.
Clorindione Tibolone may increase the anticoagulant activities of Clorindione.
Diphenadione Tibolone may increase the anticoagulant activities of Diphenadione.
Tioclomarol Tibolone may increase the anticoagulant activities of Tioclomarol.
Melagatran Tibolone may increase the anticoagulant activities of Melagatran.
Saruplase Tibolone may increase the anticoagulant activities of Saruplase.
(S)-Warfarin Tibolone may increase the anticoagulant activities of (S)-Warfarin.
Tocopherylquinone Tibolone may increase the anticoagulant activities of Tocopherylquinone.
Dabigatran Tibolone may increase the anticoagulant activities of Dabigatran.
Troxerutin Tibolone may increase the anticoagulant activities of Troxerutin.
Edetic acid Tibolone may increase the anticoagulant activities of Edetic acid.
Reviparin Tibolone may increase the anticoagulant activities of Reviparin.
Dermatan sulfate Tibolone may increase the anticoagulant activities of Dermatan sulfate.
SR-123781A Tibolone may increase the anticoagulant activities of SR-123781A.
Prasterone The risk or severity of adverse effects can be increased when Prasterone is combined with Tibolone.
Exemestane The therapeutic efficacy of Exemestane can be decreased when used in combination with Tibolone.
Hyaluronidase (ovine) The therapeutic efficacy of Hyaluronidase (ovine) can be decreased when used in combination with Tibolone.
Hyaluronidase (human recombinant) The therapeutic efficacy of Hyaluronidase (human recombinant) can be decreased when used in combination with Tibolone.
Hyaluronidase The therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Tibolone.
Lenalidomide Tibolone may increase the thrombogenic activities of Lenalidomide.
Ospemifene The risk or severity of adverse effects can be increased when Tibolone is combined with Ospemifene.
Ropinirole Tibolone may increase the excretion rate of Ropinirole which could result in a lower serum level and potentially a reduction in efficacy.
Thalidomide Tibolone may increase the thrombogenic activities of Thalidomide.
Cetuximab Tibolone may increase the thrombogenic activities of Cetuximab.
Human immunoglobulin G Tibolone may increase the thrombogenic activities of Human immunoglobulin G.
Omalizumab Tibolone may increase the thrombogenic activities of Omalizumab.
Adalimumab Tibolone may increase the thrombogenic activities of Adalimumab.
Gemtuzumab ozogamicin Tibolone may increase the thrombogenic activities of Gemtuzumab ozogamicin.
Indium In-111 satumomab pendetide Tibolone may increase the thrombogenic activities of Indium In-111 satumomab pendetide.
Infliximab Tibolone may increase the thrombogenic activities of Infliximab.
Trastuzumab Tibolone may increase the thrombogenic activities of Trastuzumab.
Rituximab Tibolone may increase the thrombogenic activities of Rituximab.

Target Protein

Estrogen receptor ESR1

Referensi & Sumber

Artikel (PubMed)
  • PMID: 15337246
    Kloosterboer HJ: Tissue-selectivity: the mechanism of action of tibolone. Maturitas. 2004 Aug 30;48 Suppl 1:S30-40. doi: 10.1016/j.maturitas.2004.02.012.
  • PMID: 17614936
    Campisi R, Marengo FD: Cardiovascular effects of tibolone: a selective tissue estrogenic activity regulator. Cardiovasc Drug Rev. 2007 Summer;25(2):132-45. doi: 10.1111/j.1527-3466.2007.00007.x.
  • PMID: 16339391
    Steckelbroeck S, Oyesanmi B, Jin Y, Lee SH, Kloosterboer HJ, Penning TM: Tibolone metabolism in human liver is catalyzed by 3alpha/3beta-hydroxysteroid dehydrogenase activities of the four isoforms of the aldo-keto reductase (AKR)1C subfamily. J Pharmacol Exp Ther. 2006 Mar;316(3):1300-9. doi: 10.1124/jpet.105.091587. Epub 2005 Dec 8.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Tibella
    Tablet • 2.5 mg • Oral • Canada • Approved

Sekuens Gen/Protein (FASTA)

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