Identification

Name
Bazedoxifene
Accession Number
DB06401
Description

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
Thumb
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

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics
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.

TargetActionsOrganism
AEstrogen receptor alpha
antagonist
agonist
Humans
UEstrogen receptor betaNot AvailableHumans
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.

Hover over products below to view reaction partners

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
Learn about our commercial Adverse Effects data.
Learn More
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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.
DrugInteraction
AdenineThe metabolism of Bazedoxifene can be decreased when combined with Adenine.
AmitriptylineThe metabolism of Bazedoxifene can be decreased when combined with Amitriptyline.
AtazanavirThe metabolism of Bazedoxifene can be decreased when combined with Atazanavir.
CarbamazepineThe serum concentration of Bazedoxifene can be decreased when it is combined with Carbamazepine.
DacomitinibThe metabolism of Bazedoxifene can be decreased when combined with Dacomitinib.
DasabuvirThe metabolism of Bazedoxifene can be decreased when combined with Dasabuvir.
DeferasiroxThe metabolism of Bazedoxifene can be decreased when combined with Deferasirox.
DesogestrelThe metabolism of Bazedoxifene can be increased when combined with Desogestrel.
EfavirenzThe metabolism of Bazedoxifene can be increased when combined with Efavirenz.
EltrombopagThe metabolism of Bazedoxifene can be decreased when combined with Eltrombopag.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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

Product Ingredients
IngredientUNIICASInChI Key
Bazedoxifene acetateJ70472UD3D198481-33-3OMZAMQFQZMUNTP-UHFFFAOYSA-N
International/Other Brands
Viviant
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
DuaveeBazedoxifene acetate (20 mg/1) + Conjugated estrogens (0.45 mg/1)Tablet, film coatedOralU.S. Pharmaceuticals2013-11-15Not applicableUs
DuaveeBazedoxifene acetate (20 mg/1) + Conjugated estrogens (0.45 mg/1)Tablet, film coatedOralWyeth Pharmaceuticals Llc, a Subsidiary of Pfizer Inc.2013-10-03Not applicableUs
DuaveeBazedoxifene acetate (20 mg/1) + Conjugated estrogens (0.45 mg/1)Tablet, film coatedOralU.S. Pharmaceuticals2013-11-15Not applicableUs
DuaviveBazedoxifene (20 mg) + Conjugated estrogens (0.45 mg)Tablet, multilayer, extended releaseOralPfizer Canada Ulc2016-12-20Not applicableCanada
DuaviveBazedoxifene (20 mg) + Conjugated estrogens (0.45 mg)Tablet, multilayer, extended releaseOralPfizer Europe Ma Eeig2014-12-16Not applicableEu

Categories

ATC Codes
G03XC02 — BazedoxifeneG03CC07 — Conjugated estrogens and bazedoxifene
Drug Categories
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

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
  1. Gruber C, Gruber D: Bazedoxifene (Wyeth). Curr Opin Investig Drugs. 2004 Oct;5(10):1086-93. [PubMed:15535430]
  2. 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. [PubMed:18072873]
KEGG Drug
D03062
PubChem Compound
154257
PubChem Substance
310264867
ChemSpider
135921
BindingDB
50099585
RxNav
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
PhaseStatusPurposeConditionsCount
4CompletedNot AvailablePostmenopausal Osteoporosis (PMO)1
4CompletedPreventionBMI >30 kg/m2 / Glucose Homeostasis / Postmenopausal Syndrome1
4CompletedPreventionRheumatoid Arthritis1
4RecruitingTreatmentSchizo Affective Disorder / Schizophrenia / Schizophreniform Disorders1
4SuspendedBasic ScienceDepression / Perimenopausal Disorder1
3CompletedDiagnosticVulvovaginal Atrophy1
3CompletedPreventionEndometrial Hyperplasia / Osteoporosis1
3CompletedPreventionOne to five years postmenopausal / Osteoporosis1
3CompletedPreventionOsteoporosis1
3CompletedTreatmentEndometrial Hyperplasia / Osteoporosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, film coatedOral20 MG
Tablet, film coatedOral
TabletOral0.45 MG/20MG
Tablet, multilayer, extended releaseOral
Tablet, delayed release0.45 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5998402No1999-12-072017-04-04Us
US6479535No2002-11-122019-05-06Us
US7138392No2006-11-212017-04-04Us
US7683051No2010-03-232027-03-10Us
US8815934No2014-08-262019-05-06Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000564 mg/mLALOGPS
logP6.03ALOGPS
logP6.01ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)9.63ChemAxon
pKa (Strongest Basic)9.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.86 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity141.9 m3·mol-1ChemAxon
Polarizability54.06 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Zinc ion binding
Specific 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 tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Gruber C, Gruber D: Bazedoxifene (Wyeth). Curr Opin Investig Drugs. 2004 Oct;5(10):1086-93. [PubMed:15535430]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. 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. [PubMed:15961563]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Lusin TT, Mrhar A, Trontelj J: UGT1A1*28 polymorphism influences glucuronidation of bazedoxifene. Pharmazie. 2015 Feb;70(2):94-6. [PubMed:25997248]
  2. 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. [PubMed:20516255]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A8
Uniprot ID
Q9HAW9
Uniprot Name
UDP-glucuronosyltransferase 1-8
Molecular Weight
59741.035 Da
References
  1. 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. [PubMed:20516255]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein kinase c binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 Da
References
  1. 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. [PubMed:20516255]

Drug created on March 19, 2008 10:29 / Updated on June 12, 2020 10:52

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