OSPHENA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OSPHENA (OSPHENA).
Selective estrogen receptor modulator (SERM) that acts as an estrogen agonist on bone and lipid metabolism, and as an estrogen antagonist on breast and uterine tissue. It mimics estrogen's effects on bone by reducing bone resorption and increasing bone mineral density.
| Metabolism | Extensively metabolized in the liver via glucuronidation (UGT1A8, UGT1A10, UGT2B7) and to a lesser extent by cytochrome P450 (CYP3A4, CYP2C19). Undergoes enterohepatic recycling. Half-life is approximately 5.7 days. |
| Excretion | Following oral administration, 50% of a radiolabeled dose is excreted in urine and 35% in feces within 168 hours, primarily as glucuronide conjugates; <1% is excreted unchanged. |
| Half-life | The terminal elimination half-life of ospemifene is approximately 26 hours (range 22-39 hours), supporting once-daily dosing. |
| Protein binding | Ospemifene is >99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The apparent volume of distribution (Vd/F) is approximately 2.4 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Absolute bioavailability is approximately 30% after oral administration due to first-pass metabolism. |
| Onset of Action | Symptomatic improvement in dyspareunia (moderate to severe) may be noted within 4-12 weeks of daily oral dosing. |
| Duration of Action | The therapeutic effect persists throughout the 24-hour dosing interval with continued daily administration; symptom relief is maintained during therapy. |
| Molecular Weight | 370.49 |
60 mg orally once daily with food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: not recommended; Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established; no specific dosing guidelines. |
| Geriatric use | No specific dose adjustment; monitor for dysphagia and esophageal adverse effects. |
| 1st trimester | Contraindicated in pregnancy. Ospemifene is an estrogen agonist/antagonist with potential for fetal harm. Animal studies show embryofetal toxicity and teratogenicity. |
| 2nd trimester | Contraindicated in pregnancy. Avoid use due to risk of fetal harm. |
| 3rd trimester | Contraindicated in pregnancy. Avoid use due to risk of fetal harm and potential effects on labor. |
Clinical note
Comprehensive clinical and safety monograph for OSPHENA (OSPHENA).
| Placental transfer | Ospemifene crosses the placenta in animal studies. Human data are lacking, but due to molecular weight (contributes to transfer) and lipophilicity, placental transfer is expected. |
| Breastfeeding | No data on presence in human milk. Ospemifene is lipophilic and may be excreted into milk. Due to potential for serious adverse reactions in nursing infants, breastfeeding should be discontinued or the drug avoided. |
■ FDA Black Box Warning
Increased risk of venous thromboembolic events (including deep vein thrombosis and pulmonary embolism) and death due to stroke. Use is contraindicated in women with active or past history of venous thromboembolism.
| Serious Effects |
PregnancyUndiagnosed abnormal genital bleedingKnown or suspected estrogen-sensitive malignant conditions (e.g., breast cancer)Active or history of venous thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism)Hypersensitivity to ospemifene or any component
| Precautions | Increased risk of venous thromboembolic events and stroke; consider risk-benefit in women at risk for these events. May cause hot flashes and leg cramps. Use with caution in patients with hepatic impairment or history of cholestasis. Not recommended for use in premenopausal women. Discontinue if prolonged immobilization occurs. Monitor lipid profile; may cause small reductions in HDL cholesterol. |
| Food/Dietary | No specific food interactions; take with food to minimize gastrointestinal side effects. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Ospemifene is contraindicated in pregnancy. Based on its mechanism as a selective estrogen receptor modulator (SERM) and animal studies showing embryotoxicity and teratogenicity, there is potential for fetal harm. First trimester exposure may increase risk of congenital anomalies; second/third trimester exposure may cause urogenital tract abnormalities and endocrine disruption. |
| Fetal Monitoring | Monitor for signs of thromboembolism, endometrial hyperplasia, and ovarian cysts. In pregnant patients, serial fetal ultrasound for urogenital and endocrine development. No specific maternal serum markers. |
| Fertility Effects | May impair fertility due to antiestrogenic effects on endometrium and ovulation; reversible upon discontinuation. No long-term studies on human fertility. |
| Clinical Pearls | Ospemifene is a selective estrogen receptor modulator (SERM) indicated for moderate to severe dyspareunia due to vulvar and vaginal atrophy in postmenopausal women. Avoid in women with estrogen-dependent neoplasia, unexplained genital bleeding, or prior thromboembolic events. Monitor for endometrial hyperplasia because uterine stimulation can occur. Not for use in premenopausal women. |
| Patient Advice | Take daily with food to reduce nausea. · Do not take if you have a history of blood clots, breast cancer, or uterine cancer. · Report any unusual vaginal bleeding, breast pain, or leg swelling immediately. · May cause hot flashes, vaginal discharge, or muscle spasms. · Use proper lubricants during intercourse; this medicine does not protect against STIs. · Continue regular pelvic exams and mammograms as recommended. |