Introduction
Ospemifene is an oral selective estrogen receptor modulator (SERM) approved for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), in postmenopausal women who are not candidates for local vaginal estrogen therapy. It represents a novel non-estrogen treatment option for genitourinary syndrome of menopause.
Mechanism of Action
Ospemifene exerts mixed estrogen agonist/antagonist effects in a tissue-selective manner. It acts as an estrogen agonist on vaginal epithelium, increasing superficial cells and decreasing parabasal cells, thereby reversing vaginal atrophy. Simultaneously, it acts as an estrogen antagonist on breast and endometrial tissue, minimizing the risk of estrogen-dependent malignancies.
Indications
- FDA-approved: Treatment of moderate to severe dyspareunia due to postmenopausal vulvar and vaginal atrophy
- FDA-approved: Treatment of moderate to severe vaginal dryness due to postmenopausal vulvar and vaginal atrophy
Dosage and Administration
- Standard dosage: 60 mg orally once daily with food
- Administration: Take with food to improve absorption
- Duration: Long-term treatment as clinically indicated
- Special populations:
- Renal impairment: No dosage adjustment necessary - Hepatic impairment: Use with caution in moderate to severe impairment - Geriatric patients: No dosage adjustment required
Pharmacokinetics
- Absorption: Bioavailability approximately 60-70%; Tmax 1.5-4 hours
- Distribution: Extensive protein binding (>99%), primarily to albumin
- Metabolism: Extensive hepatic metabolism via CYP3A4, CYP2C9, and CYP2C19
- Elimination: Primarily fecal excretion (76%), with renal excretion accounting for <1%
- Half-life: Approximately 26 hours
Contraindications
- Known or suspected estrogen-dependent neoplasia
- Active or history of venous thromboembolism (DVT, PE)
- Active or history of arterial thromboembolic disease (MI, stroke)
- Known hypersensitivity to ospemifene or any component of the formulation
- Undiagnosed abnormal genital bleeding
- Pregnancy or women who may become pregnant
Warnings and Precautions
- Venous thromboembolism: Increased risk of DVT and PE; discontinue if thromboembolic events occur
- Stroke: Increased risk of cardiovascular events
- Endometrial cancer: Monitor for any unexplained vaginal bleeding
- Cardiovascular disease: Use with caution in women with risk factors
- Hepatic impairment: Use with caution in moderate to severe impairment
- Breast cancer: Not recommended in women with known or suspected breast cancer
Drug Interactions
- CYP3A4 inducers (rifampin, carbamazepine): May decrease ospemifene concentrations
- CYP3A4 inhibitors (ketoconazole, clarithromycin): May increase ospemifene concentrations
- Warfarin: Potential for increased anticoagulant effect; monitor INR closely
- Hormone therapy: Avoid concomitant use with estrogen products
Adverse Effects
Common (>10%):- Hot flashes
- Vaginal discharge
- Muscle spasms
- Hyperhidrosis
- Headache
- Genital discharge
- Night sweats
- Vaginal hemorrhage
- Venous thromboembolism
- Stroke
- Endometrial hyperplasia
- Allergic reactions
Monitoring Parameters
- Baseline and periodic evaluation of endometrial thickness via transvaginal ultrasound
- Monitor for signs and symptoms of venous thromboembolism
- Assessment of vaginal health and symptom improvement
- Evaluation of any unexplained vaginal bleeding
- Liver function tests in patients with hepatic impairment
- Regular breast examinations and mammography as appropriate
Patient Education
- Take medication exactly as prescribed with food
- Report any signs of blood clots (leg pain/swelling, chest pain, shortness of breath)
- Immediately report any unexplained vaginal bleeding
- Regular gynecological examinations are important during treatment
- Notify all healthcare providers about ospemifene use before starting new medications
- Understand that hot flashes are a common side effect that may diminish over time
- This medication is not indicated for prevention of osteoporosis
- Use non-hormonal contraception if premenopausal status is possible
References
1. FDA Prescribing Information: Ospemifene (Osphena). 2023 2. Portman DJ, Bachmann GA, Simon JA. Ospemifene, a novel selective estrogen receptor modulator for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy. Menopause. 2013;20(6):623-630 3. Simon JA, Lin VH, Radovich C, et al. One-year long-term safety extension study of ospemifene for the treatment of vulvar and vaginal atrophy in postmenopausal women with a uterus. Menopause. 2013;20(4):418-427 4. Archer DF, Altomare C, Jiang W, et al. Ospemifene's effects on lipids and coagulation factors: a post hoc analysis of phase 2 and 3 clinical trial data. Menopause. 2017;24(10):1167-1174 5. Bachmann G, Bobula J, Mirkin S. Effects of bazedoxifene/conjugated estrogens and ospemifene on vaginal epithelium and uterine tissues. Climacteric. 2016;19(5):471-477 6. Constantine GD, Goldstein SR, Archer DF. Endometrial safety of ospemifene: results of the phase 2/3 clinical development program. Menopause. 2015;22(1):36-43