Osmifen60 mg

Osmifen is a selective estrogen receptor modulator (SERM) indicated for postmenopausal women for the treatment of:

• Moderate to severe dyspareunia (pain during sexual intercourse), a symptom of vulvar and vaginal atrophy (VVA) due to menopause.
• Moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy due to menopause.

These are the only FDA-approved indications for Osmifen; it is not approved or intended for use in premenopausal women or for any other condition.

Each film-coated tablet contains Ospemifene 60 mg as the active ingredient, along with pharmaceutically acceptable excipients including microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, hypromellose, magnesium stearate, and a film-coating system.

Osmifen is an oral, non-hormonal (non-estrogen) selective estrogen receptor modulator (SERM) used specifically to treat moderate to severe painful intercourse and vaginal dryness caused by menopausal vulvar and vaginal atrophy. Unlike estrogen therapy, Osmifen acts on estrogen receptors in a tissue-selective manner, producing estrogen-agonist effects on vaginal tissue while behaving differently in other tissues such as the endometrium. It is supplied as a 60 mg oral tablet taken once daily with food.

Osmifen belongs to the therapeutic class of Selective Estrogen Receptor Modulators (SERMs), used specifically for the management of menopausal vulvovaginal atrophy symptoms.

Ospemifene is a selective estrogen receptor modulator (SERM) that acts as an estrogen receptor agonist on vaginal epithelial tissue, while exhibiting mixed agonist/antagonist activity in other tissues depending on the tissue type and estrogen receptor subtype involved. On vaginal tissue, Ospemifene increases superficial and intermediate cell numbers, decreases parabasal cells, and lowers vaginal pH, thereby reducing atrophic changes responsible for dyspareunia and dryness.

Pharmacokinetics

• Absorption: Peak plasma concentration is reached in about 2 hours; taking Ospemifene with food increases absorption 2- to 3-fold, so it should always be taken with food.
• Distribution: More than 99% bound to plasma proteins.
• Metabolism: Primarily metabolized by hepatic CYP3A4 and CYP2C9 enzymes (CYP2C19 contributes to a lesser extent) to an active metabolite, 4-hydroxyospemifene.
• Elimination: Terminal half-life is approximately 26 hours; eliminated mainly in feces (~75%) with a smaller portion in urine (~7%).

Take Osmifen by mouth once daily, always with food, as food substantially increases absorption. Swallow the tablet whole with water; do not crush, chew, or split unless directed by a physician.

Osmifen is metabolized mainly by CYP3A4 and CYP2C9, making it susceptible to clinically significant interactions with drugs affecting these enzymes:

• Fluconazole (moderate CYP2C9/CYP3A4 inhibitor): Increases Osmifen exposure substantially (~2.7-fold); concomitant use should be avoided.
• Ketoconazole and other strong CYP3A4 inhibitors: Increase Osmifen exposure and may increase the risk of adverse reactions; use with caution.
• Rifampin and other strong CYP3A4/CYP2C9 inducers: Significantly decrease Osmifen concentrations, which may reduce effectiveness; concomitant use should generally be avoided.
• Estrogens and estrogen agonists/antagonists: The safety of combining Osmifen with systemic estrogen or other estrogen agonist/antagonist products has not been studied; concomitant use is not recommended.
• Warfarin: No clinically significant effect was seen after a single dose, but patients on chronic warfarin therapy should have anticoagulation status monitored when starting Osmifen.

Always inform your physician of all medicines, supplements, and herbal products being used before starting Osmifen.

The most common side effects of Osmifen reported in clinical trials include:

• Hot flashes/hot flushes (most common)
• Vaginal discharge
• Muscle spasms
• Excessive sweating (hyperhidrosis)
• Vaginal bleeding/spotting
• Night sweats

Serious but less common risks include endometrial thickening/hyperplasia, endometrial cancer, stroke, and venous thromboembolism - see Precautions and Warnings and Contraindications for details. Report any unusual vaginal bleeding, leg swelling or pain, chest pain, or sudden weakness/vision changes to a physician immediately.

Pregnancy: Osmifen is contraindicated in pregnancy. It is intended only for postmenopausal women and has no indication in women who could become pregnant. Animal studies have shown fetal harm (embryo-fetal lethality) at doses relevant to human exposure. If pregnancy is suspected, Osmifen should be discontinued immediately and a physician consulted.

Lactation: Osmifen is not indicated for use in nursing mothers, as it is intended for postmenopausal women. It is not known whether Osmifen passes into human breast milk; animal data suggest it is present in milk at concentrations higher than in maternal plasma. Use during breastfeeding is not recommended; consult a physician if breastfeeding is being considered.

Osmifen carries important warnings that require caution:

• Endometrial effects: An increased risk of endometrial cancer has not been ruled out; endometrial thickening has been observed in clinical trials. Any unexplained or recurrent vaginal bleeding while on Osmifen should be promptly evaluated by a physician, including endometrial sampling if indicated.
• Cardiovascular and thromboembolic risk: As with other SERMs, Osmifen is associated with an increased risk of stroke and venous thromboembolism (DVT/PE). Discontinue immediately if a stroke or blood clot is suspected. Consider discontinuing at least 4-6 weeks before surgery associated with a high risk of thromboembolism, or during prolonged immobilization.
• Hot flashes: Hot flashes are a common side effect and may worsen menopausal vasomotor symptoms in some women.
• Breast cancer: Has not been adequately studied in women with breast cancer and should not be used in women with known or suspected breast cancer.
• Severe hepatic impairment: Should not be used - see Contraindications/Dosage.
• Cardiovascular risk factors (hypertension, diabetes, smoking, high cholesterol, obesity) should be appropriately managed in women using Osmifen.

There is limited clinical experience with Osmifen overdose. In case of a suspected overdose, seek immediate medical attention or contact a poison control center. Treatment should be symptomatic and supportive, as there is no specific antidote; do not attempt unsupervised home treatment.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Elderly: No overall differences in safety or effectiveness were observed between women 65 years and older and younger postmenopausal women in clinical trials; no dose adjustment is required based on age alone.

Renal impairment: No dose adjustment is needed, including in patients with severe renal impairment.

Hepatic impairment: No dose adjustment is needed in mild to moderate hepatic impairment; Osmifen is contraindicated in severe hepatic impairment (see Contraindications).

Pediatric population: Not applicable - see Pediatric Uses.

Osmifen should be used at the lowest effective dose for the shortest duration consistent with the individual patient's treatment goals and risk profile. Physicians should periodically reassess the need for continued therapy, generally at least annually.

Selective Estrogen Receptor Modulator (SERM); non-hormonal estrogen agonist/antagonist used in menopausal vulvovaginal atrophy.

Ospemifene works as a selective estrogen receptor modulator (SERM), binding to estrogen receptors and producing tissue-selective effects. In vaginal epithelial tissue, it behaves as an estrogen receptor agonist, promoting maturation of the vaginal epithelium (increasing superficial cells, reducing parabasal cells) and lowering vaginal pH toward premenopausal levels. This reverses the atrophic changes of the vaginal mucosa that cause dryness and painful intercourse after menopause. Its activity in other estrogen-sensitive tissues (such as the endometrium) differs from its vaginal action, which underlies both its warnings and its distinct pharmacologic profile compared with systemic estrogen therapy.

Osmifen is not indicated for use in children or adolescents. It is approved solely for postmenopausal women, and clinical studies of Osmifen have not been conducted in the pediatric population. Safety and effectiveness in pediatric patients have not been established.