OSPHENA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OSPHENA (OSPHENA).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for OSPHENA (OSPHENA).

Breastfeeding	No data on human milk excretion. Ospemifene may suppress lactation due to estrogenic effects. M/P ratio unknown. Avoid breastfeeding during treatment and for at least 2 weeks after last dose.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

Active or past history of venous thromboembolism (DVT, PE, retinal vein thrombosis), pregnancy (can cause fetal harm), women who are or may become pregnant, nursing mothers, patients with hypersensitivity to raloxifene or any component of the formulation.

Clinical Precautions

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.

Clinical Tips & Counseling

Drug interactions

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OSPHENA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OSPHENA (OSPHENA).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for OSPHENA (OSPHENA).

Breastfeeding	No data on human milk excretion. Ospemifene may suppress lactation due to estrogenic effects. M/P ratio unknown. Avoid breastfeeding during treatment and for at least 2 weeks after last dose.
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.