Important Safety Information
There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. 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.
The Women's Health Initiative (WHI) estrogen alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women during 7.1 years of treatment with daily oral conjugated estrogens (CE) alone, relative to placebo. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women during 5.6 years of treatment with daily oral CE combined with medroxyprogesterone acetate (MPA), relative to placebo.
The WHI Memory Study (WHIMS) estrogen alone study reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE alone, relative to placebo. The WHIMS estrogen plus progestin study reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE combined with MPA, relative to placebo. It is unknown whether these findings apply to younger postmenopausal women.
The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer.
Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia.
Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.
PREMARIN should not be used in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or a history of breast cancer; known or suspected estrogen-dependent neoplasia; active deep vein thrombosis, pulmonary embolism, or a history of these conditions; active arterial thromboembolic disease (ie, stroke, myocardial infarction), or a history of these conditions; anaphylactic reaction or angioedema to PREMARIN; liver dysfunction or disease; thrombophilic disorders; pregnancy.
In a clinical trial, the most commonly reported (≥5%) adverse events for PREMARIN tablets that were statistically different than placebo included vaginal moniliasis, vaginitis, vaginal bleeding, dysmenorrhea, and leg cramps.
PREMARIN is indicated in the treatment of moderate to severe vasomotor symptoms due to menopause, treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, and the prevention of postmenopausal osteoporosis.
When prescribing solely for the symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered.
Updated June 22, 2010. Accessed June 13, 2011. 19. US Food and Drug Administration. Compounded menopausal hormone therapy questions and answers.
Updated February 5, 2010. Accessed June 13, 2011. 20. US Food and Drug Administration. Menopause.
Updated April 29, 2011. Accessed June 13, 2011. 21. Utian WH, Shoupe D, Bachmann G, Pinkerton JV, Pickar JH. Relief of vasomotor symptoms and vaginal atrophy with lower doses of conjugated equine estrogens and medroxyprogesterone acetate. Fertil Steril. 2001;75(6):1065-1079.