Ospemifene
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: ENDOMETRIAL CANCER and CARDIOVASCULAR DISORDERS WARNING: ENDOMETRIAL CANCER and CARDIOVASCULAR DISORDERS See full prescribing information for complete boxed warning. OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Perform adequate diagnostic measures, including directed and random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ].
Estrogen-alone therapy has an increased risk of stroke and deep vein thrombosis (DVT). OSPHENA 60 mg had cerebral thromboembolic and hemorrhagic stroke incidence rates of 1.13 and 3.39 per thousand women years, respectively vs. 3.15 and 0 per thousand women years, respectively with placebo. For deep vein thrombosis, the incidence rate for OSPHENA 60 mg is 2.26 per thousand women years (2 reported cases) vs. 3.15 per thousand women years (1 reported case) with placebo [see Warnings and Precautions (5.1) ]. Endometrial Cancer OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects.
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Perform adequate diagnostic measures, including directed and random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ]. Cardiovascular Disorders In the clinical trials for OSPHENA (duration of treatment up to 15 months), the incidence rates of thromboembolic and hemorrhagic stroke were 1.13 and 3.39 per thousand women years, respectively in the OSPHENA 60 mg treatment group and 3.15 and 0 with placebo [see Warnings and Precautions (5.1) ].
The incidence of DVT was 2.26 per thousand women years (2 reported cases) in the OSPHENA 60 mg treatment group and 3.15 per thousand women years (1 reported case) with placebo [see Warnings and Precautions (5.1) ]. OSPHENA should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman. Increased risks of stroke and deep vein thrombosis (DVT) are reported in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo as part of the…
Handling and access
NIOSH hazardous drug
Table 2NIOSH lists ospemifene as a hazardous drug. AHFS class: 68:16.12 estrogen agonist-antagonists.
- Meets the NIOSH definition of a hazardous drug (carcinogenicity, developmental or reproductive toxicity, organ toxicity at low doses, or genotoxicity) without MSHI or a Group 1 or 2A carcinogen classification.
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Estrogen Agonist/Antagonist
Dosing in kidney impairment
Renal Impairment The pharmacokinetics of ospemifene in women with severe renal impairment (CrCL <30 mL/min) was similar to those in women with normal renal function [see Clinical Pharmacology ]. No dose adjustment of OSPHENA is required in women with renal impairment.
Dosing in liver impairment
Hepatic Impairment The pharmacokinetics of ospemifene has not been studied in women with severe hepatic impairment (Child-Pugh Class C); therefore, do not use OSPHENA in women with severe hepatic impairment [see Warnings and Precautions , and Clinical Pharmacology ]. No clinically important pharmacokinetic differences with OSPHENA were observed between women with mild to moderate hepatic impairment and healthy women [see Clinical Pharmacology ].
No dose adjustment of OSPHENA is required in women with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.
Drug interactions
Check ospemifene against a medication listLabel text (8 paragraphs)
7 DRUG INTERACTIONS OSPHENA is primarily metabolized by CYP3A4 and CYP2C9. CYP2C19 and other pathways contribute to the metabolism of ospemifene. Do not use estrogens or estrogen agonist/antagonist concomitantly with OSPHENA. ( 7.1 , 12.3 ) Do not use fluconazole concomitantly with OSPHENA. Fluconazole increases serum concentrations of OSPHENA. ( 7.2 , 12.3 ) Do not use rifampin concomitantly with OSPHENA. Rifampin decreases serum concentration of OSPHENA. ( 7.2 , 12.3 )
7.1 Estrogens and Estrogen Agonist/Antagonist Do not use OSPHENA concomitantly with estrogens and estrogen agonists/antagonists. The safety of concomitant use of OSPHENA with estrogens and estrogen agonists/antagonists has not been studied.
7.2 Fluconazole Do not use OSPHENA concomitantly with fluconazole, a moderate CYP3A / strong CYP2C9 / moderate CYP2C19 inhibitor. Fluconazole increases the systemic exposure of ospemifene by 2.7-fold. Administration of fluconazole with ospemifene may increase the risk of OSPHENA-related adverse reactions [see Clinical Pharmacology (12.3) ] .
7.3 Rifampin Rifampin, a strong CYP3A4 / moderate CYP2C9 / moderate CYP2C19 inducer, decreases the systemic exposure of ospemifene by 58%. Therefore, co-administration of OSPHENA with drugs such as rifampin which induce CYP3A4, CYP2C9 and/or CYP2C19 activity would be expected to decrease the systemic exposure of ospemifene, which may decrease the clinical effect [see Clinical Pharmacology (12.3) ] .
7.4 Ketoconazole Ketoconazole, a strong CYP3A4 inhibitor, increases the systemic exposure of ospemifene by 1.4-fold. Administration of ketoconazole chronically with ospemifene may increase the risk of OSPHENA-related adverse reactions [see Clinical Pharmacology (12.3) ] .
7.5 Warfarin Repeated administration of ospemifene had no effect on the pharmacokinetics of a single 10 mg dose of warfarin. No study was conducted with multiple doses of warfarin. The effect of ospemifene on clotting time such as the International Normalized Ratio (INR) or prothrombin time (PT) was not studied [see Clinical Pharmacology (12.3) ] .
7.6 Highly Protein-Bound Drugs Ospemifene is more than 99% bound to serum proteins and might affect the protein binding of other drugs. Use of OSPHENA with other drug products that are highly protein-bound may lead to increased exposure of either that drug or ospemifene [see Clinical Pharmacology (12.3) ] .
7.7 Multiple Enzyme Inhibition Co-administration of OSPHENA with a drug known to inhibit CYP3A4 and CYP2C9 isoenzymes may increase the risk of OSPHENA-related adverse reactions.
Contraindications
4 CONTRAINDICATIONS OSPHENA is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding. Estrogen-dependent neoplasia. Active DVT, PE, or a history of these conditions. Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions. Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) to OSPHENA or any ingredients. OSPHENA is contraindicated in women who are or may become pregnant. OSPHENA may cause fetal harm when administered to a pregnant woman.
Ospemifene was embryo-fetal lethal with labor difficulties and increased pup deaths in rats at doses below clinical exposures, and embryo-fetal lethal in rabbits at 10 times the clinical exposure based on mg/m 2 . If this drug is used during pregnancy, or if a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to a fetus.
Undiagnosed abnormal genital bleeding ( 4 ) Estrogen-dependent neoplasia ( 4 , 5.2 ) Active DVT, pulmonary embolism (PE), or a history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke and myocardial infarction [MI]), or a history of these conditions ( 4 , 5.1 ) Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) to OSPHENA or any ingredients ( 4 ) Known or suspected pregnancy ( 4 , 8.1 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for ospemifene. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Not Recommended During Pregnancy OSPHENA is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to a fetus [see Contraindications (4) ]. Based on animal data, OSPHENA is likely to increase the risk of adverse outcomes during pregnancy and labor. Adverse findings at maternally toxic doses included embryofetal lethality in rats and rabbits, and neonatal mortality and difficult labor in rats. The reproductive effects observed are consistent with and are considered to be related to estrogen receptor activity of OSPHENA.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data The effects of ospemifene on embryo-fetal development were studied in rats (0.1, 1, or 4 mg/kg/day) and rabbits (3, 10, or 30 mg/kg/day) when treated from implantation through organogenesis [Gestation Day (GD) 6-16 in the rat and GD6-18 in the rabbit. In rabbits, there was an increase in the incidence of total resorptions at 30 mg/kg/day (10 times the human exposure based on body surface area mg/m 2 )]. Drug-induced malformations were not observed in either rats or rabbits.
The effects of ospemifene on pre- and postnatal development were studied in pregnant rats (0.01, 0.05, and 0.25 mg/kg/day) treated from implantation (GD6) through lactation (Lactation Day (LD) 21). Pregnant rats given 0.05 or 0.25 mg/kg/day ospemifene (0.8% to 4% the human exposure based on body surface area mg/m 2 ) had a significantly prolonged and difficult gestation, increased post-implantation loss, increased number of dead pups at birth, and an increased incidence of postnatal loss. Ospemifene did not induce adverse effects in the surviving offspring of pregnant rats at drug exposures up to 4% the human exposure.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.