Ethinyl Estradiol/Norethindrone Acetate (Oral)
Cardiovascular and Other Risks
- Estrogens and progestins should not be used for the prevention of cardiovascular disease.
- WHI Study-MI, Stroke, Breast Cancer, PE, DVT:The Women's Health Initiative (WHI) Study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years) during 5 yrs of treatment with daily oral conjugated estrogens (0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo (See Package Insert)
Risk of Probable Dementia
- Estrogens and progestins should not be used for the prevention of dementia.
- WHIMS Study: Estrogens Plus Progestins-Dementia: The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during four years of treatment with daily conjugated estrogens combined with medroxyprogresterone acetate, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See package insert)
General Risk Statements
- Other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins, were not studied in the WHI clinical trials, and in the absence of comparable data, these risks should be assumed to be similar.
- Because of these risks, estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals for the individual woman.
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Use lowest possible estrogen dose to control symptoms and discontinue medication as soon as possible
- If prolonged treatment indicated, reassess patient on at least a semi-annual basis to determine need for continued therapy
- Close clinical surveillance recommended, monitor for persistent/recurrent abnormal vaginal bleeding.
- Exposure during pregnancy requires patient appraisal of potential risks.
FDA and Industry Communications
Updated January 2018