Ospemifene

Undiagnosed abnormal genital bleeding. Known or suspected estrogen-dependent neoplasia.
Active DVT, pulmonary embolism (PE), or a history of these conditions.
Active arterial thromboembolic disease [for example, stroke and myocardial infarction, or a history of these conditions.
Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) or any ingredients.
It is contraindicated in women who are or may become pregnant. It may cause fetal harm when administered to a pregnant woman. Ospemifene was embryo-fetal lethal with labor difficulties and increased pup deaths in rats at doses below clinical exposures, and embryo-fetal lethal in rabbits at 10 times the clinical exposure based on mg/m2. If this drug is used during pregnancy, or if a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to a fetus.

Cardiovascular Disorders
: Risk factors for cardiovascular disorders, arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.
Stroke
: In the clinical trials for Myfene (duration of treatment up to 15 months), the incidence rates of thromboembolic and hemorrhagic stroke were 1.13 and 3.39 per thousand women years, respectively in Myfene 60 mg treatment group and 3.15 and 0 per thousand women years in placebo.
Coronary Heart Disease
: In the clinical trials, two cases of myocardial infarction (MI) occurred in women receiving 60 mg of Myfene. In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo.
Venous Thromboembolism
: In the Myfene clinical trials, two cases of DVT occurred in women receiving Myfene 60 mg. Should a VTE occur or be suspected, Myfene should be discontinued immediately. If feasible, Myfene should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
Endometrial Cancer
: Myfene is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, Myfene has agonistic effects. In the Myfene clinical trials (60 mg treatment group), no cases of endometrial cancer were seen with exposure up to 52 weeks. There was a single case of simple hyperplasia without atypia. Endometrial thickening equal to 5 mm or greater was seen in the Myfene up to 52 weeks treatment groups at a rate of 101.4 per thousand women vs. 20.9 per thousand women for placebo. The incidence of any type of proliferative (weakly plus active plus disordered) endometrium was 26.3 per thousand women in the Myfene up to 52 weeks treatment groups vs. 0 per thousand women for placebo. Uterine polyps occurred at an incidence of 19.6 per thousand women in the Myfene up to 52 weeks treatment groups vs. 8.3 per thousand women for placebo. Clinical surveillance of all women using Myfene is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.
Breast Cancer
: Myfene 60 mg has not been adequately studied in women with breast cancer; therefore, it should not be used in women with known or suspected breast cancer.
Severe Hepatic Impairment
: Myfene should not be used in women with severe hepatic impairment
Hypersensitivity Reactions
: Inform postmenopausal women who have had hypersensitivity reactions to Myfene such as angioedema, urticaria, rash, and pruritus, that they should not take.
Vaginal Bleeding
: Inform postmenopausal women of the importance of reporting unusual vaginal bleeding to their healthcare providers as soon as possible.
Hot Flashes or Flushes
: Myfene may initiate or increase the occurrence of hot flashes in some women.
Carcinogenesis
: In a 2-year carcinogenicity study in female mice, Myfene was orally administered at 100, 400, or 1500 mg/kg/day. No evaluation for carcinogenicity was conducted in male mice. There was significant increase in adrenal subcapsular cell adenomas at 4 and 5 times the human exposure based on AUC, and adrenal cortical tumors at 5 times the human exposure. In the ovary, an increase in sex cord/stromal tumors, tubulostromal tumors, granulosa cell tumors, and luteomas were also seen. These findings occurred at doses 2 to 5 times the human exposure based on AUC and are probably related to estrogenic/antiestrogenic effect of Myfene in mice.
Mutagenesis
: Myfene was not genotoxic in vitro in the Ames test in strains of Salmonella typhimurium or at the thymidine kinase (tk) locus of mouse lymphoma L5178Y cells in the absence and in the presence of a metabolic activator system. In in vivo testing, Myfene was not genotoxic in a standard mouse bone marrow micronucleus test or in a determination of DNA adducts in the liver of rats.
Impairment of Fertility
: The effect of Myfene on fertility was not directly evaluated. In female rats and monkeys, decreases in ovarian and uterine weights, decreased corpora lutea number, increased ovarian cysts, uterine atrophy, and disrupted cycles were observed when given repeated daily oral doses. In male rats, atrophy of the prostate and seminal vesicles was noted. The effects on reproductive organs observed in animals are consistent with the estrogen receptor activity of Myfene and potential for impairment of fertility.