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Identification
- Summary
Bazedoxifene is a selective estrogen receptor modulator (SERM) used to treat moderate to severe vasomotor symptoms in menopause and osteoporosis alone or in combination with conjugated estrogens.
- Brand Names
- Duavee, Duavive
- Generic Name
- Bazedoxifene
- DrugBank Accession Number
- DB06401
- Background
Bazedoxifene is a third generation selective estrogen receptor modulator (SERM), developed by Pfizer following the completion of their takeover of Wyeth Pharmaceuticals. In late 2013, Pfizer received approval for bazedoxifene as part of the combination drug DUAVEE in the prevention (not treatment) of postmenopausal osteoporosis. It is approved in the European Union (marketed in Italy and Spain) and Japan as monotherapy. In 2013, the combination product containing conjugated estrogens and bazedoxifene was approved by the FDA for the treatment of moderate to severe vasomotor symptoms associated with menopause, as well as the prevention of postmenopausal osteoporosis in women.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Bazedoxifene (DB06401)
- Weight
- Average: 470.613
Monoisotopic: 470.256942963 - Chemical Formula
- C30H34N2O3
- Synonyms
- Bazedoxifene
- Bazedoxifeno
- External IDs
- TSE-424
- WAY 140424
- WAY-140424
- WAY-TSE-424
Pharmacology
- Indication
Indicated for following conditions alone or in combination with conjugated estrogens in women with a uterus:
Treatment of moderate to severe vasomotor symptoms associated with menopause
Prevention of postmenopausal osteoporosis
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to prevent Postmenopausal osteoporosis Combination Product in combination with: Conjugated estrogens (DB00286) •••••••••••• Used in combination to treat Moderate vasomotor symptoms Combination Product in combination with: Conjugated estrogens (DB00286) •••••••••••• Used in combination to treat Severe vasomotor symptoms Combination Product in combination with: Conjugated estrogens (DB00286) •••••••••••• - Contraindications & Blackbox Warnings
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Not Available
- Mechanism of action
Bazedoxifene belongs to a class of compounds known as selective estrogen receptor modulators (SERMs). Bazedoxifene acts as both an oestrogen-receptor agonist and/or antagonist, depending upon the cell and tissue type and target genes. Bazedoxifene decreases bone resorption and reduces biochemical markers of bone turnover to the premenopausal range. These effects on bone remodelling lead to an increase in bone mineral density (BMD), which in turn contributes to a reduction in the risk of fractures. Bazedoxifene functions primarily as an oestrogen-receptor antagonist in uterine and breast tissues.
Target Actions Organism AEstrogen receptor antagonistagonistHumans UEstrogen receptor beta Not Available Humans - Absorption
Bazedoxifene is rapidly absorbed with a tmax of approximately 2 hours and exhibits a linear increase in plasma concentrations for single doses from 0.5 mg up to 120 mg and multiple daily doses from 1 mg to 80 mg. The absolute bioavailability of bazedoxifene is approximately 6%.
- Volume of distribution
Following intravenous administration of a 3 mg dose of bazedoxifene, the volume of distribution is 14.7 ± 3.9 l/kg.
- Protein binding
98-99%.
- Metabolism
Glucuronidation is the major metabolic pathway. After peroral application, bazedoxifene is metabolized by UDP-glucuronosyltransferases (UGTs) to bazedoxifene-4'-glucuronide (M4) and bazedoxifene-5-glucuronide (M5).Little or no cytochrome P450-mediated metabolism is evident. The concentrations of this glucuronide are approximately 10-fold higher than those of unchanged active substance in plasma.
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- Route of elimination
The major route of elimination of radio-labelled bazedoxifene is the faeces, and less than 1% of the dose is eliminated in urine.
- Half-life
~30 hours.
- Clearance
The apparent oral clearance of bazedoxifene is approximately 4 to 5 l/h/kg.
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAdenine The metabolism of Bazedoxifene can be decreased when combined with Adenine. Amitriptyline The metabolism of Bazedoxifene can be decreased when combined with Amitriptyline. Asciminib The metabolism of Bazedoxifene can be decreased when combined with Asciminib. Atazanavir The metabolism of Bazedoxifene can be decreased when combined with Atazanavir. Carbamazepine The serum concentration of Bazedoxifene can be decreased when it is combined with Carbamazepine. - Food Interactions
- Administer calcium supplement. If calcium intake from food is inadequate administer calcium supplements to prevent hypocalcemia.
- Administer vitamin supplements. If dietary intake of vitamin D is inadequate, then administer vitamin D supplements to avoid deficiency of vitamin D and calcium.
- Take at the same time every day.
- Take with or without food. Taking bazedoxifene with food may increase its AUC by 25% but does not impact the Cmax.
Products
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Ingredient UNII CAS InChI Key Bazedoxifene acetate J70472UD3D 198481-33-3 OMZAMQFQZMUNTP-UHFFFAOYSA-N - International/Other Brands
- Viviant
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Conbriza Tablet, film coated 20 mg Oral Pfizer Europe Ma Eeig 2021-02-10 Not applicable EU 
Conbriza Tablet, film coated 20 mg Oral Pfizer Europe Ma Eeig 2021-02-10 Not applicable EU Conbriza Tablet, film coated 20 mg Oral Pfizer Europe Ma Eeig 2021-02-10 Not applicable EU Conbriza Tablet, film coated 20 mg Oral Pfizer Europe Ma Eeig 2021-02-10 Not applicable EU Conbriza Tablet, film coated 20 mg Oral Pfizer Europe Ma Eeig 2021-02-10 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Duavee Bazedoxifene acetate (20 mg/1) + Conjugated estrogens (0.45 mg/1) Tablet, film coated Oral U.S. Pharmaceuticals 2013-11-15 Not applicable US 
Duavee Bazedoxifene acetate (20 mg/1) + Conjugated estrogens (0.45 mg/1) Tablet, film coated Oral U.S. Pharmaceuticals 2013-11-15 Not applicable US Duavee Bazedoxifene acetate (20 mg/1) + Conjugated estrogens (0.45 mg/1) Tablet, film coated Oral Wyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc. 2013-10-03 Not applicable US Duavive Bazedoxifene acetate (20 mg) + Conjugated estrogens (0.45 mg) Tablet, multilayer, extended release Oral Pfizer Canada Ulc 2016-12-20 Not applicable Canada 
Duavive Bazedoxifene (20 mg) + Conjugated estrogens (0.45 mg) Tablet, multilayer, extended release Oral Pfizer Europe Ma Eeig 2016-09-08 Not applicable EU
Categories
- ATC Codes
- G03XC02 — Bazedoxifene
- G03XC — Selective estrogen receptor modulators
- G03X — OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G03 — SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
- G — GENITO URINARY SYSTEM AND SEX HORMONES
- Drug Categories
- Bone Density Conservation Agents
- Estrogen Agonist/Antagonist
- Estrogen Receptor Modulators
- Genito Urinary System and Sex Hormones
- Heterocyclic Compounds, Fused-Ring
- Hormone Antagonists
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Selective Estrogen Receptor Modulators
- Sex Hormones and Modulators of the Genital System
- UGT1A1 Substrates
- UGT1A4 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 2-phenylindoles. These are indoles substituted at the 2-position with a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Indoles and derivatives
- Sub Class
- Indoles
- Direct Parent
- 2-phenylindoles
- Alternative Parents
- Phenylpyrroles / N-alkylindoles / Hydroxyindoles / 3-methylindoles / Phenoxy compounds / Phenol ethers / Azepanes / Alkyl aryl ethers / 1-hydroxy-2-unsubstituted benzenoids / Heteroaromatic compounds show 4 more
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 2-phenylindole / 2-phenylpyrrole / 3-alkylindole / 3-methylindole / Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Azacycle / Azepane show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- Q16TT9C5BK
- CAS number
- 198481-32-2
- InChI Key
- UCJGJABZCDBEDK-UHFFFAOYSA-N
- InChI
- InChI=1S/C30H34N2O3/c1-22-28-20-26(34)12-15-29(28)32(30(22)24-8-10-25(33)11-9-24)21-23-6-13-27(14-7-23)35-19-18-31-16-4-2-3-5-17-31/h6-15,20,33-34H,2-5,16-19,21H2,1H3
- IUPAC Name
- 1-({4-[2-(azepan-1-yl)ethoxy]phenyl}methyl)-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol
- SMILES
- CC1=C(N(CC2=CC=C(OCCN3CCCCCC3)C=C2)C2=C1C=C(O)C=C2)C1=CC=C(O)C=C1
References
- General References
- Gruber C, Gruber D: Bazedoxifene (Wyeth). Curr Opin Investig Drugs. 2004 Oct;5(10):1086-93. [Article]
- Miller PD, Chines AA, Christiansen C, Hoeck HC, Kendler DL, Lewiecki EM, Woodson G, Levine AB, Constantine G, Delmas PD: Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study. J Bone Miner Res. 2008 Apr;23(4):525-35. [Article]
- External Links
- KEGG Drug
- D03062
- PubChem Compound
- 154257
- PubChem Substance
- 310264867
- ChemSpider
- 135921
- BindingDB
- 50099585
- 1441386
- ChEBI
- 135947
- ChEMBL
- CHEMBL46740
- ZINC
- ZINC000001895505
- PDBe Ligand
- 29S
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Bazedoxifene
- PDB Entries
- 4xi3 / 6psj
- FDA label
- Download (671 KB)
- MSDS
- Download (58.6 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Osteoporosis 2 somestatus stop reason just information to hide Not Available Completed Not Available Postmenopausal Osteoporosis 1 somestatus stop reason just information to hide Not Available Completed Other Osteoarthritis of the Hands 1 somestatus stop reason just information to hide Not Available Terminated Not Available Postmenopausal 1 somestatus stop reason just information to hide Not Available Unknown Status Treatment Pancreatic Cancer 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 20 MG Tablet, film coated Oral Tablet Oral Tablet, delayed release Oral Tablet, multilayer, extended release Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5998402 No 1999-12-07 2017-04-04 US US6479535 No 2002-11-12 2019-05-06 US US7138392 No 2006-11-21 2017-04-04 US US7683051 No 2010-03-23 2027-03-10 US US8815934 No 2014-08-26 2019-05-06 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.000564 mg/mL ALOGPS logP 6.03 ALOGPS logP 6.01 Chemaxon logS -5.9 ALOGPS pKa (Strongest Acidic) 9.63 Chemaxon pKa (Strongest Basic) 9.09 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 57.86 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 141.9 m3·mol-1 Chemaxon Polarizability 54.06 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0200900000-ae072a06f52d2ec9f2a6 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0010900000-c0bd1029aca7e5493568 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0330900000-879b86ec364330d4f0b8 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00rl-0298700000-99ca17be921042e83ab5 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-2900300000-f397fb898147c26faf22 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-0092100000-a59f2855a9e3c22fd54b Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 228.5986547 predictedDarkChem Lite v0.1.0 [M-H]- 215.6573 predictedDeepCCS 1.0 (2019) [M+H]+ 229.6014547 predictedDarkChem Lite v0.1.0 [M+H]+ 218.0153 predictedDeepCCS 1.0 (2019) [M+Na]+ 228.7226547 predictedDarkChem Lite v0.1.0 [M+Na]+ 225.20178 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- General Function
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032). Maintains neuronal survival in response to ischemic reperfusion injury when in the presence of circulating estradiol (17-beta-estradiol/E2) (By similarity)
- Specific Function
- 14-3-3 protein binding
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Gruber C, Gruber D: Bazedoxifene (Wyeth). Curr Opin Investig Drugs. 2004 Oct;5(10):1086-93. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560)
- Specific Function
- DNA binding
- Gene Name
- ESR2
- Uniprot ID
- Q92731
- Uniprot Name
- Estrogen receptor beta
- Molecular Weight
- 59215.765 Da
References
- Komm BS, Kharode YP, Bodine PV, Harris HA, Miller CP, Lyttle CR: Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology. 2005 Sep;146(9):3999-4008. Epub 2005 Jun 16. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:18177842, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18177842). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3 essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Also glucuronidates the biologically active form of vitamin D3, calcitriol, probably leading to its biliary transport and intestinal reabsorption (PubMed:18177842)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1A4
- Molecular Weight
- 60024.535 Da
References
- Lusin TT, Mrhar A, Trontelj J: UGT1A1*28 polymorphism influences glucuronidation of bazedoxifene. Pharmazie. 2015 Feb;70(2):94-6. [Article]
- Shen L, Ahmad S, Park S, DeMaio W, Oganesian A, Hultin T, Scatina J, Bungay P, Chandrasekaran A: In vitro metabolism, permeability, and efflux of bazedoxifene in humans. Drug Metab Dispos. 2010 Sep;38(9):1471-9. doi: 10.1124/dmd.109.030999. Epub 2010 Jun 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:15472229, PubMed:16595710, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15472229, PubMed:16595710, PubMed:23288867). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens and estrogens (PubMed:15472229, PubMed:16595710, PubMed:18719240, PubMed:23288867). Produces dihydrotestosterone (DHT) diglucuronide from the DHT after two subsequent glucoronidation steps (PubMed:16595710). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A8
- Uniprot ID
- Q9HAW9
- Uniprot Name
- UDP-glucuronosyltransferase 1A8
- Molecular Weight
- 59741.035 Da
References
- Shen L, Ahmad S, Park S, DeMaio W, Oganesian A, Hultin T, Scatina J, Bungay P, Chandrasekaran A: In vitro metabolism, permeability, and efflux of bazedoxifene in humans. Drug Metab Dispos. 2010 Sep;38(9):1471-9. doi: 10.1124/dmd.109.030999. Epub 2010 Jun 1. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:18719240, PubMed:19545173, PubMed:23288867, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:18719240, PubMed:23288867, PubMed:26220143). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A10
- Uniprot ID
- Q9HAW8
- Uniprot Name
- UDP-glucuronosyltransferase 1A10
- Molecular Weight
- 59809.075 Da
References
- Shen L, Ahmad S, Park S, DeMaio W, Oganesian A, Hultin T, Scatina J, Bungay P, Chandrasekaran A: In vitro metabolism, permeability, and efflux of bazedoxifene in humans. Drug Metab Dispos. 2010 Sep;38(9):1471-9. doi: 10.1124/dmd.109.030999. Epub 2010 Jun 1. [Article]
Drug created at March 19, 2008 16:29 / Updated at June 02, 2024 21:55