Version July 2025
Ospemifene is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, ospemifene 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.
In the clinical trials for ospemifene (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 ospemifene 60 mg treatment group and 3.15 and 0 with placebo. The incidence of deep vein thrombosis (DVT) was 2.26 per thousand women years (2 reported cases) in ospemifene 60 mg treatment group and 3.15 per thousand women years (1 reported case) with placebo. Ospemifene should be prescribed for the shortest duration consistent with treatment goals and risks for the individual woman.
Increased risks of stroke and 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 Women's Health Initiative (WHI).
Dosage guidance:
Clinical considerations: Generally reserved for patients who did not respond to nonhormonal therapies (ie, vaginal moisturizer, lubricant) and cannot (eg, limited mobility) or prefer not to use vaginal estrogen (Ref).
Genitourinary syndrome of menopause (vulvovaginal atrophy) (with dyspareunia and/or vaginal dryness), treatment (alternative agent): Oral: 60 mg once daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild or moderate impairment (Child-Turcotte-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Turcotte-Pugh class C): Use is not recommended.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Endocrine & metabolic: Hot flash (7% to 12%)
1% to 10%:
Central nervous system: Headache (3%)
Dermatologic: Hyperhidrosis (1% to 3%), night sweats (1%)
Genitourinary: Endometrial hyperplasia (10%), vaginal discharge (4% to 6%), endometrial polyps (2%), vaginal hemorrhage (1%)
Neuromuscular & skeletal: Muscle spasm (2% to 5%)
<1%, postmarketing, and/or case reports: Angioedema, benign neoplasm, cerebrovascular accident, cyst, deep vein thrombosis, endometrial carcinoma, erythematous rash, hypersensitivity reaction, malignant neoplasm, myocardial infarction, polyp, pruritus, pulmonary embolism, skin rash, thrombosis, urticaria
Hypersensitivity (eg, angioedema, urticaria, rash, pruritus) to ospemifene or any component of the formulation; undiagnosed abnormal genital bleeding; active deep vein thrombosis, pulmonary embolism, or a history of these conditions; active arterial thromboembolic disease (eg, stroke, myocardial infarction) or a history of these conditions; estrogen-dependent neoplasia; patients who are or may become pregnant.
Concerns related to adverse effects:
• Breast cancer: Estrogen with or without progestogen for the management of menopausal symptoms may be associated with an increased risk of breast cancer. Ospemifene has not been adequately studied in patients with breast cancer. Use is not currently recommended in patients with carcinoma of the breast (known, suspected or history of).
• Endometrial cancer: The use of unopposed estrogen in patients with a uterus is associated with an increased risk of endometrial cancer. Perform adequate diagnostic measures, including endometrial sampling if indicated, to rule out malignancy in patients who are postmenopausal with undiagnosed abnormal vaginal bleeding.
Disease-related concerns:
• Cardiovascular disease: Adverse cardiovascular events may occur; manage risk factors for cardiovascular disorders, arterial vascular disorders, and/or venous thromboembolism (VTE) appropriately. Risk factors include diabetes mellitus, hypercholesterolemia, hypertension, SLE, obesity, tobacco use, and/or history of VTE. Discontinue immediately if a VTE, thromboembolic, or hemorrhagic stroke occur or are suspected.
• Hepatic dysfunction: Has not been studied in patients with severe hepatic impairment; use is not recommended.
Special populations:
• Surgical patients: Whenever possible, discontinue at least 4 to 6 weeks prior to elective surgery associated with an increased risk of thromboembolism or during periods of prolonged immobilization.
Other warnings/precautions:
• Risks vs benefits: Use for the shortest duration possible consistent with treatment goals and risks for the individual patient. With appropriate clinical monitoring, use may continue as long as bothersome symptoms are present (NAMS 2020).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Osphena: 60 mg
No
Tablets (Osphena Oral)
60 mg (per each): $9.76
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Osphena: 60 mg
Administer with food.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Genitourinary syndrome of menopause (vulvovaginal atrophy) with dyspareunia and/or vaginal dryness, treatment: Treatment of genitourinary syndrome of menopause (vulvovaginal atrophy) with dyspareunia and/or vaginal dryness.
Note: The International Society for the Study of Women’s Sexual Health and The North American Menopause Society have endorsed the term genitourinary syndrome of menopause (GSM) as new terminology for vulvovaginal atrophy. The term GSM encompasses all genital and urinary signs and symptoms associated with a loss of estrogen due to menopause (Portman 2014).
Ospemifene may be confused with osimertinib, raloxifene, toremifene
Substrate of CYP2C19 (Minor), CYP2C9 (Minor), CYP3A4 (Major with inhibitors), CYP3A4 (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Apalutamide: May decrease serum concentration of Ospemifene. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Ospemifene. Risk C: Monitor
Dicloxacillin: May decrease serum concentration of Ospemifene. Risk C: Monitor
Enzalutamide: May decrease serum concentration of Ospemifene. Risk C: Monitor
Estrogen Derivatives: May increase adverse/toxic effects of Ospemifene. Risk X: Avoid
Fluconazole: May increase serum concentration of Ospemifene. Risk X: Avoid
Fluoroestradiol F18: Coadministration of Selective Estrogen Receptor Modulators and Fluoroestradiol F18 may alter diagnostic results. Risk X: Avoid
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
MiFEPRIStone: May increase serum concentration of Ospemifene. Risk C: Monitor
RifAMPin: May decrease serum concentration of Ospemifene. Risk C: Monitor
Selective Estrogen Receptor Modulators: May increase adverse/toxic effects of Ospemifene. Ospemifene may also enhance adverse/toxic effects of other Selective Estrogen Receptor Modulators. Risk X: Avoid
Use is contraindicated in patients who may become pregnant.
Use is contraindicated in patients who are pregnant.
It is not known if ospemifene is present in human milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Evaluate baseline risk for breast cancer and CVD prior to therapy. Efficacy and side effects beginning 1 to 3 months after starting therapy, then every 6 to 12 months as appropriate; age appropriate breast and pelvic exams; blood pressure; unscheduled bleeding lasting >6 months for endometrial pathology (sooner in patients who are obese, diabetic, or have a history of endometrial cancer). Duration of treatment should be evaluated at least annually (ES [Stuenkel 2015]).
Ospemifene is a selective estrogen receptor modulator (SERM); it activates estrogen pathways in some tissues and blocks estrogen pathways in others, and specifically has agonistic effects on the endometrium. In women with VVA, ospemifene was shown to improve vaginal changes associated with the decrease in natural estrogen production associated with menopause (improves vaginal maturation index, decreases vaginal pH) and significantly decreased the most bothersome moderate-to-severe subjective findings reported by women (vaginal dryness and dyspareunia) after 12 weeks of therapy (Bachmann, 2010).
Onset of action: A significant decrease in vaginal dryness and dyspareunia were observed after 12 weeks of therapy (Bachmann, 2010).
Distribution: Vd: 448 L
Protein binding: >99% bound to serum proteins
Metabolism: Hepatic via CYP3A4, 2C9, and 2C19; forms a metabolite (4-hydroxyospemifene)
Bioavailability: Increased approximately two- to threefold by food
Half-life elimination: ~26 hours
Time to peak: ~2 hours (range: 1-8 hours)
Excretion: Feces (75%); urine (7%; <0.2% as unchanged drug)
