Estradiol Hemihydrate (1 brand name, 1 dosage form, 1 route)
Available dosage forms: EMULSION.
Routes of administration: TOPICAL.
Brand Names
- ESTRASORB
Boxed Warning
Estrogen and progestin combinations, including MYFEMBREE, increase the risk of thrombotic or thromboembolic disorders including pulmonary embolism (PE), deep vein thrombosis (DVT), stroke and myocardial infarction (MI), especially in women at increased risk for these events [see Warnings and Precautions (5.1)]. MYFEMBREE is contraindicated in women with current or a history of thrombotic or thromboembolic disorders and in women at increased risk for these events, including women over 35 years of age who smoke or women with uncontrolled hypertension [see Contraindications (4)].
Contraindications
MYFEMBREE is contraindicated in women: With a high risk of arterial, venous thrombotic, or thromboembolic disorders [see Boxed Warning and Warnings and Precautions (5.1)]. Examples include women over 35 years of age who smoke and women who are known to have: current or history of deep vein thrombosis or pulmonary embolism vascular disease (e.g., cerebrovascular disease, coronary artery disease, peripheral vascular disease) thrombogenic valvular or thrombogenic rhythm diseases of the heart (e.g., subacute bacterial endocarditis with valvular disease, or atrial fibrillation) inherited or acquired hypercoagulopathies uncontrolled hypertension headaches with focal neurological symptoms or migraine headaches with aura if over 35 years of age Who are pregnant. Exposure to MYFEMBREE early in pregnancy may increase the risk of early pregnancy loss [see Warnings and Precautions (5.9) and Use in Specific Populations (8.1)]. With known osteoporosis, because of the risk of further bone loss [see Warnings and Precautions (5.2)]. With current or history of breast cancer or other hormone-sensitive malignancies, and with increased risk for hormone-sensitive malignancies [see Warnings and Precautions (5.3)]. With known hepatic impairment or disease [see Warnings and Precautions (5.5)]. With undiagnosed abnormal uterine bleeding. With known anaphylactic reaction, angioedema, or hypersensitivity to MYFEMBREE or any of its components. Anaphylactoid reactions, urticaria, and angioedema have been reported [see Warnings and Precautions (5.14), Adverse Reactions (6.2)].
Adverse Reactions
The following clinically significant adverse reactions are discussed elsewhere in the labeling: Thromboembolic Disorders and Vascular Events [see Warnings and Precautions (5.1)] Bone Loss [see Warnings and Precautions (5.2)] Suicidal Ideation and Mood Disorders (Including Depression) [see Warnings and Precautions (5.4)] Hepatic Impairment and Transaminase Elevations [see Warnings and Precautions (5.5)] Elevated Blood Pressure [see Warnings and Precautions (5.7)] Change in Menstrual Bleeding Pattern and Reduced Ability to Recognize Pregnancy [see Warnings and Precautions (5.8)] Uterine Fibroid Prolapse or Expulsion [see Warnings and Precautions (5.10)] Alopecia [see Warnings and Precautions (5.11)] Effects on Carbohydrate and Lipid Metabolism [see Warnings and Precautions (5.12)] Hypersensitivity Reactions [see Warnings and Precautions (5.14)]
Mechanism of Action
MYFEMBREE is a combination of relugolix, estradiol (E2), and norethindrone acetate (NETA). Relugolix is a non-peptide GnRH receptor antagonist that competitively binds to pituitary GnRH receptors, thereby reducing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to decreased serum concentrations of the ovarian sex hormones estradiol and progesterone and reduced bleeding associated with uterine fibroids and pain associated with endometriosis. Estradiol acts by binding to nuclear receptors that are expressed in estrogen-responsive tissues. As a component of MYFEMBREE, the addition of exogenous estradiol may reduce the increase in bone resorption and resultant bone loss that can occur due to a decrease in circulating estrogen concentrations from relugolix alone. Progestins such as norethindrone act by binding to nuclear receptors that are expressed in progesterone-responsive tissues. As a component of MYFEMBREE, norethindrone may protect the uterus from the potential adverse endometrial effects of unopposed estrogen.
Overdosage
Overdosage of estrogen plus progestin may cause nausea, vomiting, breast tenderness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. Supportive care is recommended if an overdose occurs. The amount of relugolix, estradiol, or norethindrone removed by hemodialysis is unknown.