OSPEMIFENE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OSPEMIFENE (OSPEMIFENE).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OSPEMIFENE (OSPEMIFENE).

Breastfeeding	It is unknown whether ospemifene is excreted in human breast milk. No M/P ratio is available. Due to potential serious adverse effects in the nursing infant, breastfeeding is not recommended during treatment and for one week after the last dose.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Undiagnosed abnormal genital bleeding","Known or suspected estrogen-sensitive cancer (e.g., breast cancer)","Active or history of venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism)","Pregnancy or women who may become pregnant"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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OSPEMIFENE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for OSPEMIFENE (OSPEMIFENE).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for OSPEMIFENE (OSPEMIFENE).

Breastfeeding	It is unknown whether ospemifene is excreted in human breast milk. No M/P ratio is available. Due to potential serious adverse effects in the nursing infant, breastfeeding is not recommended during treatment and for one week after the last dose.
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.

Warnings & precautions

■ 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.