Ospemifene

⛔ FDA Black Box Warning

WARNING: ENDOMETRIAL CANCER and CARDIOVASCULAR DISORDERS WARNING: ENDOMETRIAL CANCER and CARDIOVASCULAR DISORDERS See full prescribing information for complete boxed warning. OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Perform adequate diagnostic measures, including directed and random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ]. Estrogen-alone therapy has an increased risk of stroke and deep vein thrombosis (DVT). OSPHENA 60 mg had cerebral thromboembolic and hemorrhagic stroke incidence rates of 1.13 and 3.39 per thousand women years, respectively vs. 3.15 and 0 per thousand women years, respectively with placebo. For deep vein thrombosis, the incidence rate for OSPHENA 60 mg is 2.26 per thousand women years (2 reported cases) vs. 3.15 per thousand women years (1 reported case) with placebo [see Warnings and Precautions (5.1) ]. Endometrial Cancer OSPHENA is an estrogen agonist/antagonist with tissue selective effects. In the endometrium, OSPHENA has estrogen agonistic effects. There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Perform adequate diagnostic measures, including directed and random endometrial sampling when indicated, to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions (5.2) ]. Cardiovascular Disorders In the clinical trials for OSPHENA (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 the OSPHENA 60 mg treatment group and 3.15 and 0 with placebo [see Warnings and Pr

Contraindications

4 CONTRAINDICATIONS OSPHENA is contraindicated in women with any of the following conditions: Undiagnosed abnormal genital bleeding. Estrogen-dependent neoplasia. Active DVT, PE, or a history of these conditions. Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions. Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) to OSPHENA or any ingredients. OSPHENA is contraindicated in women who are or may become pregnant. OSPHENA 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/m 2 . 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. Undiagnosed abnormal genital bleeding ( 4 ) Estrogen-dependent neoplasia ( 4 , 5.2 ) Active DVT, pulmonary embolism (PE), or a history of these conditions ( 4 , 5.1 ) Active arterial thromboembolic disease (for example, stroke and myocardial infarction [MI]), or a history of these conditions ( 4 , 5.1 ) Hypersensitivity (for example, angioedema, urticaria, rash, pruritus) to OSPHENA or any ingredients ( 4 ) Known or suspected pregnancy ( 4 , 8.1 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Not Recommended During Pregnancy OSPHENA is contraindicated in women who are or may become pregnant. 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 [see Contraindications (4) ]. Based on animal data, OSPHENA is likely to increase the risk of adverse outcomes during pregnancy and labor. Adverse findings at maternally toxic doses included embryofetal lethality in rats and rabbits, and neonatal mortality and difficult labor in rats. The reproductive effects observed are consistent with and are considered to be related to estrogen receptor activity of OSPHENA. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data The effects of ospemifene on embryo-fetal development were studied in rats (0.1, 1, or 4 mg/kg/day) and rabbits (3, 10, or 30 mg/kg/day) when treated from implantation through organogenesis [Gestation Day (GD) 6-16 in the rat and GD6-18 in the rabbit. In rabbits, there was an increase in the incidence of total resorptions at 30 mg/kg/day (10 times the human exposure based on body surface area mg/m 2 )]. Drug-induced malformations were not observed in either rats or rabbits. The effects of ospemifene on pre- and postnatal development were studied in pregnant rats (0.01, 0.05, and 0.25 mg/kg/day) treated from implantation (GD6) through lactation (Lactation Day (LD) 21). Pregnant rats given 0.05 or 0.25 mg/kg/day ospemifene (0.8% to 4% the human exposure based on body surface area mg/m 2 ) had a significantly prolonged and difficult gestation, increased post-implantation loss, increased number of dead pups at birth, and an increased incidence of postnatal loss. Ospemifene did not induce adverse effects in the surviving offspring of pregnant rats at drug exposures up to 4% the human exposure.