Identification
- Summary
Ospemifene is a non-hormonal estrogen receptor modulator (SERM) used to treat moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.
- Brand Names
- Osphena
- Generic Name
- Ospemifene
- DrugBank Accession Number
- DB04938
- Background
Ospemifene is a new selective non-hormonal estrogen receptor modulator (SERM) that is used for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. FDA approved on February 26, 2013.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ospemifene (DB04938)
- Weight
- Average: 378.891
Monoisotopic: 378.138657687 - Chemical Formula
- C24H23ClO2
- Synonyms
- 2-(4-(4-Chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol
- 2-(p-((Z)-4-Chloro-1,2-diphenyl-1-butenyl)phenoxy)ethanol
- Deamino-hydroxytoremifene
- Ospemifene
- Ospemifeno
- External IDs
- FC-1271
- FC-1271A
Pharmacology
- Indication
Ospemifene is indicated for the treatment of moderate to severe dyspareunia and vaginal dryness associated with menopause.7
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- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
The half maximal inhibitory concentration (IC50) for estrogen receptor (ER) alpha and beta are 0.8 μM and 1.7 μM, respectively. Ospemifene has potential uses in the management of osteoporosis in postmenopausal women. It interacts with osteoblasts and osteoclasts in such a way that it reduces bone turnover. It also has potential uses in the prevention of breast cancer. Studies suggest that ospemifene, in a dose-dependent manner, reduces the incidence of tumours.
- Mechanism of action
Ospemifene is a next generation SERM (selective estrogen receptor modulator) that selectively binds to estrogen receptors and either stimulates or blocks estrogen's activity in different tissue types. It has an agonistic effect on the endometrium.
Target Actions Organism AEstrogen receptor alpha antagonistagonistHumans - Absorption
When a single oral dose of ospemifene 60 mg is given to postmenopausal women under fasted conditions, the pharmacokinetic parameters are as follows: Tmax = 2 hours (range of 1 - 8 hours); Cmax = 533 ng/mL; AUC (0-inf) = 4165 ng•hr/mL. When the same aforementioned dose is given to postmenopausal women under fed conditions, the pharmacokinetic parameters are as follows: Tmax = 2.5 hours (1 - 6 hours); Cmax = 1198 ng/mL; AUC (0-inf) = 7521 ng•hr/mL. Accumulation occurs following repeated doses. Time to steady state = 9 days.
Although the bioavailability of ospemifene has not been formally evaluated, it is expected to have a low bioavailability because of its lipophilic nature.- Volume of distribution
448 L
- Protein binding
>99% bound to serum proteins
- Metabolism
Ospemifene is hepatically metabolized via CYP3A4, CYP2C9, CYP2C19, and CYP2B6. The major metabolite was 4-hydroxyospemifene, 25% of the parent compound will undergo this biotransformation. Other metabolites include 4'-hydroxy-ospemifene, <7% of the parent compound will undergo this biotransformation. In order of decreasing potency, ospemifene was suggested to be a weak inhibitor for CYP2B6, CYP2C9, CYP2C19, CYP2C8, CYP2D6 and CYP3A4.
- Route of elimination
Following an oral administration of ospemifene, approximately 75% and 7% of the dose was excreted in feces and urine, respectively. Less than 0.2% of the ospemifene dose was excreted unchanged in urine.
- Half-life
Terminal half-life = 26 hours .
- Clearance
Total body clearance = 9.16 L/hr.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Adverse reactions (≥1 percent) include: hot flush, vaginal discharge, muscle spasms, genital discharge, hyperhidrosis.
- 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 softwareAbametapir The serum concentration of Ospemifene can be increased when it is combined with Abametapir. Abatacept The metabolism of Ospemifene can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Ospemifene. Acebutolol The metabolism of Acebutolol can be decreased when combined with Ospemifene. Acenocoumarol The metabolism of Ospemifene can be decreased when combined with Acenocoumarol. Acetaminophen The metabolism of Acetaminophen can be decreased when combined with Ospemifene. Acetohexamide The metabolism of Ospemifene can be decreased when combined with Acetohexamide. Acetyl sulfisoxazole The metabolism of Ospemifene can be decreased when combined with Acetyl sulfisoxazole. Acetylsalicylic acid The metabolism of Ospemifene can be decreased when combined with Acetylsalicylic acid. Adalimumab The metabolism of Ospemifene can be increased when combined with Adalimumab. 
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- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Osphena Tablet 60 mg Oral Duchesnay Inc. 2022-01-13 Not applicable Canada 
Osphena Tablet, film coated 60 mg/1 Oral SHIONOGI INC. 2013-02-26 Not applicable US 
Osphena Tablet, film coated 60 mg/1 Oral Pharma Packaging Solutions 2013-02-26 Not applicable US Senshio Tablet 60 mg Oral Shionogi B.V. 2020-12-22 Not applicable EU 
Senshio Tablet 60 mg Oral Shionogi B.V. 2020-12-22 Not applicable EU Senshio Tablet 60 mg Oral Shionogi B.V. 2020-12-22 Not applicable EU
Categories
- ATC Codes
- G03XC05 — Ospemifene
- Drug Categories
- Benzene Derivatives
- Benzylidene Compounds
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Estrogen Agonist-antagonists
- Estrogen Agonist/Antagonist
- Genito Urinary System and Sex Hormones
- Selective Estrogen Receptor Modulators
- Sex Hormones and Modulators of the Genital System
- Stilbenes
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Stilbenes
- Sub Class
- Not Available
- Direct Parent
- Stilbenes
- Alternative Parents
- Diphenylmethanes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Primary alcohols / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides
- Substituents
- Alcohol / Alkyl aryl ether / Alkyl chloride / Alkyl halide / Aromatic homomonocyclic compound / Benzenoid / Diphenylmethane / Ether / Hydrocarbon derivative / Monocyclic benzene moiety
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- aromatic ether, organochlorine compound, primary alcohol (CHEBI:73275)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- B0P231ILBK
- CAS number
- 128607-22-7
- InChI Key
- LUMKNAVTFCDUIE-VHXPQNKSSA-N
- InChI
- InChI=1S/C24H23ClO2/c25-16-15-23(19-7-3-1-4-8-19)24(20-9-5-2-6-10-20)21-11-13-22(14-12-21)27-18-17-26/h1-14,26H,15-18H2/b24-23-
- IUPAC Name
- 2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethan-1-ol
- SMILES
- OCCOC1=CC=C(C=C1)C(=C(\CCCl)C1=CC=CC=C1)\C1=CC=CC=C1
References
- Synthesis Reference
Marja Sodervall, Maire Eloranta, Arja Kalapudas, Brian Kearton, Michael McKenzie, "METHODS FOR THE PREPARATION OF FISPEMIFENE FROM OSPEMIFENE." U.S. Patent US20080214860, issued September 04, 2008.
US20080214860- General References
- Taras TL, Wurz GT, DeGregorio MW: In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer. J Steroid Biochem Mol Biol. 2001 Jun;77(4-5):271-9. [Article]
- Voipio SK, Komi J, Kangas L, Halonen K, DeGregorio MW, Erkkola RU: Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Maturitas. 2002 Nov 20;43(3):207-14. [Article]
- Rutanen EM, Heikkinen J, Halonen K, Komi J, Lammintausta R, Ylikorkala O: Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial. Menopause. 2003 Sep-Oct;10(5):433-9. [Article]
- Ylikorkala O, Cacciatore B, Halonen K, Lassila R, Lammintausta R, Rutanen EM, Heikkinen J, Komi J: Effects of ospemifene, a novel SERM, on vascular markers and function in healthy, postmenopausal women. Menopause. 2003 Sep-Oct;10(5):440-7. [Article]
- Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [Article]
- McCall JL, DeGregorio MW: Pharmacologic evaluation of ospemifene. Expert Opin Drug Metab Toxicol. 2010 Jun;6(6):773-9. doi: 10.1517/17425255.2010.487483. [Article]
- FDA Approved Drug Products: Osphena (ospemifene) tablets for oral use [Link]
- External Links
- KEGG Drug
- D08958
- PubChem Compound
- 3036505
- PubChem Substance
- 175426911
- ChemSpider
- 2300501
- 1370971
- ChEBI
- 73275
- ChEMBL
- CHEMBL2105395
- ZINC
- ZINC000001550766
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Ospemifene
- FDA label
- Download (350 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Painful Intercourse / Vulvo Vaginal Atrophy 1 4 Recruiting Health Services Research Genitourinary Syndrome of Menopause (GSM) / Sexual; Disorder, Arousal, Female / Vulvovaginal signs and symptoms 1 4 Terminated Treatment Sexual Dysfunctions, Physiological 1 3 Completed Treatment Atrophy / Vaginal Diseases 5 3 Completed Treatment Vaginal Dryness 1 2 Completed Treatment Atrophy / Vaginal Diseases 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 60 mg Tablet, film coated Oral 60 mg/1 Tablet, film coated Oral 60 MG Tablet, film coated Oral 60.0 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8470890 No 2013-06-25 2024-02-13 US US6245819 No 2001-06-12 2020-07-21 US US8236861 No 2012-08-07 2026-08-11 US US8772353 No 2014-07-08 2024-02-13 US US9241915 No 2016-01-26 2024-02-13 US US8642079 No 2014-02-04 2028-07-09 US US9566252 No 2017-02-14 2020-07-21 US US9855224 No 2018-01-02 2024-02-13 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Insoluble FDA label - Predicted Properties
Property Value Source Water Solubility 0.000526 mg/mL ALOGPS logP 5.7 ALOGPS logP 5.56 ChemAxon logS -5.9 ALOGPS pKa (Strongest Acidic) 15.1 ChemAxon pKa (Strongest Basic) -2.8 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 1 ChemAxon Polar Surface Area 29.46 Å2 ChemAxon Rotatable Bond Count 8 ChemAxon Refractivity 121.68 m3·mol-1 ChemAxon Polarizability 41.97 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five No ChemAxon Ghose Filter Yes ChemAxon Veber's Rule Yes ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9972 Blood Brain Barrier + 0.7095 Caco-2 permeable + 0.6894 P-glycoprotein substrate Non-substrate 0.587 P-glycoprotein inhibitor I Inhibitor 0.7541 P-glycoprotein inhibitor II Inhibitor 0.5935 Renal organic cation transporter Non-inhibitor 0.6587 CYP450 2C9 substrate Non-substrate 0.7712 CYP450 2D6 substrate Non-substrate 0.8459 CYP450 3A4 substrate Non-substrate 0.5552 CYP450 1A2 substrate Non-inhibitor 0.5168 CYP450 2C9 inhibitor Non-inhibitor 0.7604 CYP450 2D6 inhibitor Non-inhibitor 0.8754 CYP450 2C19 inhibitor Inhibitor 0.5512 CYP450 3A4 inhibitor Non-inhibitor 0.7578 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6072 Ames test Non AMES toxic 0.597 Carcinogenicity Non-carcinogens 0.767 Biodegradation Not ready biodegradable 0.5073 Rat acute toxicity 2.3083 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.5657 hERG inhibition (predictor II) Non-inhibitor 0.6556
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntagonistAgonist
- 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
- Komi J, Heikkinen J, Rutanen EM, Halonen K, Lammintausta R, Ylikorkala O: Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women. Gynecol Endocrinol. 2004 Mar;18(3):152-8. [Article]
- Wurz GT, Read KC, Marchisano-Karpman C, Gregg JP, Beckett LA, Yu Q, Degregorio MW: Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice. J Steroid Biochem Mol Biol. 2005 Nov;97(3):230-40. Epub 2005 Sep 8. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
Drug created at October 21, 2007 22:23 / Updated at August 16, 2022 17:13