Ospemifene is an estrogen agonist/antagonist used for the treatment of moderate to severe dyspareunia, which is a symptom of vulvar and vaginal atrophy associated with menopause.

Ospemifene is a next-generation selective estrogen receptor modulator (SERM) that binds selectively to estrogen receptors and can either activate or block estrogenic activity depending on the tissue type. It shows an agonistic effect on the endometrium.

Treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause: 60 mg tablet with food once daily.

Treatment of moderate to severe vaginal dryness, a symptom of vulvar and vaginal atrophy, due to menopause: 60 mg tablet with food once daily.

Ospemifene is mainly metabolized by CYP3A4 and CYP2C9 enzymes, while CYP2C19 and other pathways also contribute to its metabolism.

Estrogens and Estrogen Agonist/Antagonist: Ospemifene should not be used together with estrogens or estrogen agonists/antagonists. The safety of this combination has not been established.

Fluconazole: Fluconazole is a moderate CYP3A, strong CYP2C9, and moderate CYP2C19 inhibitor. It should not be co-administered with Ospemifene because it increases Ospemifene exposure by about 2.7 times, which may increase the risk of adverse effects.

Rifampin: Rifampin is a strong CYP3A4 and moderate CYP2C9/CYP2C19 inducer. It reduces Ospemifene exposure by approximately 58%, which may reduce its clinical effectiveness.

Ketoconazole: Ketoconazole increases Ospemifene exposure by about 1.4-fold. Long-term use may increase the risk of adverse reactions.

Warfarin: Ospemifene does not significantly alter the pharmacokinetics of warfarin. However, its effect on INR or prothrombin time has not been evaluated.

Highly Protein-Bound Drugs: Ospemifene is more than 99% protein-bound and may displace or be affected by other highly protein-bound drugs, potentially altering drug exposure.

Multiple Enzyme Inhibition: Co-administration with drugs that inhibit CYP3A4 and CYP2C9 may increase the risk of Ospemifene-related adverse reactions.

• Undiagnosed abnormal genital bleeding. Known or suspected estrogen-dependent neoplasia.
• Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history of these conditions.
• Active arterial thromboembolic disease (e.g., stroke, myocardial infarction) or a history of these conditions.
• Hypersensitivity reactions (e.g., angioedema, urticaria, rash, pruritus) to Ospemifene or any of its ingredients.

Ospemifene is contraindicated in women who are pregnant or may become pregnant. It may cause fetal harm when used during pregnancy. Animal studies showed embryo-fetal lethality, labor complications, and increased pup mortality in rats at exposures below clinical levels, and embryo-fetal lethality in rabbits at about 10 times the clinical exposure (based on mg/m²). If exposure occurs during pregnancy, the patient should be informed about potential fetal risk.

• Cardiovascular disorders.
• Malignant neoplasms.
• Vascular disorders: hot flush.
• Reproductive system and breast disorders: vaginal discharge.
• Musculoskeletal and connective tissue disorders: muscle spasms.
• Skin and subcutaneous tissue disorders: hyperhidrosis.

Use in Pregnancy: Ospemifene is contraindicated in women who are or may become pregnant. If exposure occurs during pregnancy, patients should be informed about the potential risk to the fetus. Animal data suggest increased risk of adverse pregnancy and labor outcomes, including embryo-fetal death in rats and rabbits, neonatal mortality, and difficult labor in rats at maternally toxic doses. These effects are consistent with estrogen receptor activity of Ospemifene.

Use in Lactation: It is not known whether Ospemifene is excreted in human breast milk. There are no data on its effects on the breastfed infant or milk production. Breastfeeding should be avoided during treatment. Ospemifene has been detected in rat milk.

Cardiovascular Disorders Risk factors for cardiovascular disease and thromboembolism (such as hypertension, diabetes, smoking, hypercholesterolemia, obesity, personal or family history of VTE, and systemic lupus erythematosus) should be properly managed before and during treatment.

Stroke In clinical trials (up to 15 months), thromboembolic and hemorrhagic stroke rates with Ospemifene 60 mg were 1.13 and 3.39 per 1,000 women-years, compared to 3.15 and 0 in placebo.

Coronary Heart Disease In trials, two cases of myocardial infarction occurred in women receiving Ospemifene 60 mg. In estrogen-alone studies, no overall increase in coronary heart disease events was observed compared to placebo.

Venous Thromboembolism (VTE) Two cases of deep vein thrombosis were reported in clinical trials with Ospemifene. If VTE is suspected, the drug should be stopped immediately. It should be discontinued 4–6 weeks before major surgery or prolonged immobilization when possible.

Endometrial Cancer Ospemifene has estrogen agonist/antagonist activity in a tissue-selective manner and shows agonist effects in the endometrium. No endometrial cancer cases were seen up to 52 weeks of use, but hyperplasia, endometrial thickening, and uterine polyps were reported more frequently than placebo. Women with unexplained persistent or recurrent abnormal vaginal bleeding should be evaluated for malignancy.

Breast Cancer Ospemifene has not been adequately studied in breast cancer patients and should not be used in women with known or suspected breast cancer.

Severe Hepatic Impairment Ospemifene should not be used in women with severe liver impairment.

Hypersensitivity Reactions Patients with previous hypersensitivity reactions such as angioedema, urticaria, rash, or itching should not use Ospemifene.

Vaginal Bleeding Postmenopausal women should report any abnormal vaginal bleeding promptly to a healthcare provider.

Hot Flashes Ospemifene may cause or worsen hot flashes in some patients.

Carcinogenesis In long-term animal studies, Ospemifene increased adrenal and ovarian tumors in mice at exposures several times higher than human levels. These effects are believed to be related to its estrogenic/antiestrogenic activity.

Mutagenesis Ospemifene showed no genotoxic effects in bacterial tests, mouse lymphoma assay, bone marrow micronucleus test, or rat DNA adduct studies.

Impairment of Fertility Animal studies showed effects on reproductive organs, including reduced ovarian and uterine weights, ovarian cysts, uterine atrophy, and disrupted cycles in females, and prostate and seminal vesicle atrophy in males. These findings are consistent with its estrogen receptor activity and suggest possible fertility impairment.

Pediatric Use: Ospemifene is not indicated for use in children. No clinical studies have been performed in the pediatric population.

Geriatric Use: In clinical trials involving 2,209 women treated with Ospemifene, more than 19% were aged 65 years or older. No meaningful differences in safety or effectiveness were observed between elderly and younger women under 65 years.

Renal Impairment; In women with severe renal impairment (CrCL <30 mL/min), the pharmacokinetics of Ospemifene were similar to those with normal kidney function. No dose adjustment is required in renal impairment.

Hepatic Impairment :Ospemifene has not been studied in women with severe hepatic impairment (Child-Pugh Class C). Therefore, it should not be used in these patients.

Drugs used in vaginal and vulval conditions.

Store below 30°C, protect from light and moisture, and keep out of reach of children.