Estradiol/Norethindrone Acetate

DEA Class; Rx

Common Brand Names; Activella, CombiPatch, Lopreeza, Mimvey

Indicated for treatment of moderate to severe vasomotor symptoms (hot flashes) of menopause and/or related genitourinary symptoms including atrophic vaginitis, vulvar atrophy (kraurosis vulvae), whether menopause is natural or surgical (e.g., due to oophorectomy).

Hypersensitivity, including anaphylaxis or angioedema to estrogen/progestins Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Pregnancy

Estrogen-dependent neoplasia

Current/history of DVT/PE, arterial thromboembolic disease, breast cancer, liver disease/tumors

Undiagnosed abnormal vaginal bleeding

• Amenorrhea
• Breakthrough bleeding
• Change in menstrual flow
• Spotting
• Edema
• Anorexia
• Weakness
• Change in weight
• Depression
• Dizziness
• Headache
• Nervousness
• Somnolence
• Breast tenderness
• Galactorrhea
• Abdominal pain
• Nausea/vomiting
• Cholestatic jaundice
• Deep vein thrombosis
• Thrombophlebitis
• Endometrial hyperplasia
• Endocervical polyp
• Uterine leiomyomata
• Fallopian tube cyst
• Uterine spasms
• Breast cancer
• Hypertension
• Varicose veins
• Jaundice cholestatic
• Cholelithiasis
• Gall bladder disorder
• Transaminases increased
• Skin discoloration
• Lability affected
• Libido disorder
• Migraine
• Vertigo
• Paresthesia
• Angioedema
• Hypersensitivity
• Weight increased

Caution in patients with bone mineral density changes, current/history of depression, DM, HTN, hyperlipidemia, hypertriglyceridemia, obesity, endometriosis, family history of breast cancer & DVT/PE, smoking, epilepsy, migraine, renal/cardiac impairment; discontinue estrogen with or without progestogen, if DVT/PE, stroke or MI occur or suspected

Discontinue if the following develop: jaundice, visual problems, 4-6 wk before major surgery, any symptoms of VTE, massive BP increase, unusually severe migraines or first-time migraines, depression

The WHI estrogen plus progestin substudy reported increased risk (not statistically significant) of coronary heart disease (CHD) events (defined as nonfatal MI, silent MI, or CHD death) in women receiving daily CE plus MPA compared to women receiving placebo; an increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5; the WHI estrogen-alone substudy reported no overall effect on CHD events in women receiving estrogen-alone compared to placebo

Increased risk of post-op thromboembolic complications; if feasible, discontinue 4-6 wk before major surgery or the type associated with increased risk of thromboembolism, or during periods of prolonged immobilization

History of migraine with aura reported with therapy

In some epidemiologic studies, use of estrogen plus progestin and estrogen-only products, in particular for 5 or more years, has been associated with increased risk of ovarian cancer; however, duration of exposure associated with increased risk is not consistent across all epidemiologic studies and some report no association

Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases; if hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce serum calcium levels

Angioedema involving eye/eyelid, face, larynx, pharynx, tongue and extremity (hands, legs, ankles, and fingers) with or without urticaria requiring medical intervention has occurred in postmarketing; women who develop angioedema anytime during course of treatment should not receive it again; exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema; consider whether benefits of estrogen therapy outweigh risks in such women

Cases of anaphylactic/ anaphylactoid reactions, which developed anytime during course of treatment and required emergency medical management, reported in postmarketing setting

In women with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis; consider discontinuation of treatment if pancreatitis occurs

Not indicated for use in pregnancy; there are no data with use of in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac abnormalities and limb-reduction defects) following exposure to combined hormonal contraceptives (estrogen and progestins) before conception or during early pregnancy

Estrogens plus progestogens are present in human milk and can reduce milk production in breastfeeding women; this reduction can occur at any time but is less likely to occur once breastfeeding is well established; the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from therapy or from underlying maternal condition