OSPEMIFENE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OSPEMIFENE (OSPEMIFENE).
Ospemifene is a selective estrogen receptor modulator (SERM) that acts as an agonist on estrogen receptors in vaginal tissues, leading to proliferation and maturation of vaginal epithelium, while exhibiting antagonist activity on breast and endometrial tissues.
| Metabolism | Primarily metabolized via CYP3A4 and CYP2C9, with minor contributions from CYP2C19, CYP2C8, and CYP2B6. Undergoes glucuronidation and sulfation. |
| Excretion | Primarily hepatic metabolism with biliary excretion; < 30% renal elimination as metabolites. Fecal excretion accounts for approximately 70% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 26 hours (range 20–30 hours), supporting once-daily dosing. |
| Protein binding | > 99% bound to serum proteins, primarily albumin. |
| Volume of Distribution | Approximately 4.2 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 20–30% due to first-pass metabolism. |
| Onset of Action | Oral administration: maximum plasma concentrations reached in 2–4 hours; clinical effects on vaginal epithelium seen within 4–8 weeks of daily dosing. |
| Duration of Action | Sustained effect on vaginal pH and maturation index with continued daily use; effects diminish over 2–4 weeks after discontinuation. |
| Molecular Weight | 389.5 |
60 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥15 mL/min). Not studied in severe renal impairment (CrCl <15 mL/min) or dialysis. |
| Liver impairment | Contraindicated in Child-Pugh Class C (severe hepatic impairment). No dose adjustment for Child-Pugh Class A or B; use with caution. |
| Pediatric use | Not indicated for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; pharmacokinetics similar to younger adults. Monitor for vulvovaginal atrophy and thromboembolic risks. |
| 1st trimester | Contraindicated due to potential teratogenicity; animal studies show embryo-fetal toxicity. |
| 2nd trimester | Contraindicated; may cause fetal harm based on antiestrogen activity. |
| 3rd trimester | Contraindicated; risk of fetal growth restriction and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for OSPEMIFENE (OSPEMIFENE).
| Placental transfer | Ospemifene is a nonsteroidal estrogen agonist/antagonist; animal studies indicate placental transfer and fetal exposure. |
| Breastfeeding | Not recommended during breastfeeding due to potential serious adverse reactions in nursing infants; drug or metabolites may be excreted in milk. |
| Lactation Rating |
■ FDA Black Box Warning
There is an increased risk of endometrial cancer in women with an intact uterus. Use only when necessary and consider periodic endometrial evaluation.
| Serious Effects |
Hypersensitivity to ospemifene or any componentUndiagnosed abnormal genital bleedingKnown or suspected estrogen-dependent neoplasiaActive or past history of venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism)Active liver disease or impaired liver function (e.g., Child-Pugh Class A, B, C)
| Precautions | Endometrial cancer risk, Cardiovascular and cerebrovascular events (not evaluated in long-term studies), Venous thromboembolism (potential risk), Breast cancer (long-term safety not established), Use with caution in patients with hepatic impairment |
| Food/Dietary | Take with food to minimize GI side effects. No specific food restrictions; however, avoid grapefruit juice as it may increase drug levels via CYP3A4 inhibition. |
Loading safety data…
| L5 |
| Teratogenic Risk | Ospemifene is contraindicated in pregnancy due to potential fetal harm. In animal studies, it caused fetal malformations (e.g., skeletal abnormalities) and embryo-fetal loss. There are no adequate human data; however, based on its estrogenic and antiestrogenic activity, it may interfere with fetal development. Use is not recommended at any trimester. |
| Fetal Monitoring | If unintentional exposure occurs during pregnancy, monitor fetal growth and development via ultrasound. In general, no specific maternal monitoring beyond routine prenatal care is required, but assess for signs of estrogenic side effects (e.g., thromboembolic events). |
| Fertility Effects | Ospemifene may impair fertility in females of reproductive potential. In animal studies, it disrupted estrous cycles and caused ovarian changes. The effect on human fertility is unknown; however, it should be avoided in women attempting conception until further data are available. |
| Clinical Pearls | Ospemifene is a selective estrogen receptor modulator (SERM) indicated for moderate to severe dyspareunia due to vulvar and vaginal atrophy (VVA) in postmenopausal women. It has estrogenic effects on vaginal tissue but antiestrogenic effects on breast and endometrium. Monitor for thromboembolic events; contraindicated in history of VTE or PE. Not for use in women with breast cancer or estrogen-dependent neoplasia. May cause hot flashes and vaginal discharge. |
| Patient Advice | Take one 60 mg tablet daily with food to reduce gastrointestinal upset. · Notify your healthcare provider if you experience unusual vaginal bleeding, breast pain, or lumps. · Seek immediate medical attention for signs of blood clots: chest pain, shortness of breath, leg swelling or pain, sudden severe headache. · Do not use if you have a history of blood clots, breast cancer, or liver disease. · Ospemifene is for non-surgical women postmenopausal; it does not prevent pregnancy or sexually transmitted infections. · Avoid smoking and limit alcohol intake to reduce the risk of blood clots. |