PREMARIN: A blend of estrogens with extensive evidence to support your recommendation3-17
- Evidence supports starting appropriate symptomatic menopausal women on estrogen therapy22
- No increased risk of invasive breast cancer with PREMARIN after an average follow-up of 7.1 years3
- No increased risk of coronary heart disease with PREMARIN after an average follow-up of 7.1 years23
- A significant increased risk of stroke and DVT associated with PREMARIN after an average follow-up of 7.1 years4,23
- Significant relief of moderate to severe vasomotor symptoms in as early as 3 weeks6
Findings on breast cancer
Evidence supports starting appropriate symptomatic menopausal women on estrogen therapy.22 Data from the Women’s Health Initiative (WHI) trial show that in all age groups, there was no increased risk of invasive breast cancer with PREMARIN after an average follow-up of 7.1 years.3
Adjudicated data from the WHI Estrogen-Alone Substudy, a prospective, randomized, double‑blind trial comparing estrogen alone with placebo in 10,739 women aged 50-79 years who had undergone a hysterectomy.
The use of estrogens has been reported to result in an increase in abnormal mammograms requiring further evaluation.22
Effect on vasomotor symptoms
PREMARIN can provide significant relief of moderate to severe vasomotor symptoms as early as 3 weeks.6 In the Women’s Health, Osteoporosis, Progestin, Estrogen (HOPE) Study, a randomized, double-blind trial comparing PREMARIN with placebo in 2,673 healthy, postmenopausal women with an intact uterus (including an efficacy-evaluable population, n=241 at baseline in the vasomotor substudy):
- 84% reduction in the number of hot flashes by week 4 with PREMARIN 0.625 mg (n=27)6.22
- 94% reduction in the number of hot flashes by week 12 with PREMARIN 0.625 mg (n=27)6.22
Effect on bone mineral density
In the 2-year Women’s Hope Study, PREMARIN provided a significant increase in spine and hip bone mineral density.2,7
* Data from the Women’s HOPE Study: a 2-year study of 2,673 healthy postmenopausal women
(average age of 53.3 years). The BMD substudy included 822 women.
† Modified intent-to-treat population.
‡ Differences from baseline and placebo were significant (P<0.05).
§ P=0.02 for 0.3 mg vs. 0.625 mg.
Percentages rounded to nearest tenth.
All subjects received one 600-mg tablet of Caltrate® daily.
Range of dosing options
PREMARIN has been shown to provide symptom relief and bone protection at every dose: 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg.6.7,22
Important Safety Information
WARNINGS
ENDOMETRIAL CANCER
Adequate diagnostic measures, including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. (See WARNINGS, Malignant neoplasms, Endometrial cancer in the Prescribing Information.)
CARDIOVASCULAR AND OTHER RISKS
Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Dementia in the Prescribing Information.)
The estrogen alone substudy of the Women’s Health Initiative (WHI) reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 6.8 years and 7.1 years, respectively, of treatment with daily oral conjugated estrogens (CE 0.625 mg), relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders in the Prescribing Information.)
The estrogen plus progestin substudy of WHI reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and DVT in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily CE 0.625 mg combined with medroxyprogesterone acetate (MPA 2.5 mg), relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular disorders and Malignant neoplasms, Breast cancer in the Prescribing Information.)
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 5.2 years of treatment with daily CE 0.625 mg alone and during 4 years of treatment with daily CE 0.625 mg combined with MPA 2.5 mg, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL STUDIES and WARNINGS, Dementia and PRECAUTIONS, Geriatric Use in the Prescribing Information.)
In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA and other combinations and dosage forms of estrogens and progestins. 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 and risks for the individual woman.
PREMARIN is indicated in the treatment of moderate to severe vasomotor symptoms due to menopause, the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, and the prevention of postmenopausal osteoporosis.
PREMPRO is indicated in women who have a uterus for the treatment of moderate to severe vasomotor symptoms due to menopause, the treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, and the prevention of postmenopausal osteoporosis.
PREMARIN Vaginal Cream is indicated in the treatment of atrophic vaginitis and kraurosis vulvae and the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.
When prescribing solely for the treatment of 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 for whom non-estrogen medications are not considered to be appropriate.
PREMARIN, PREMPRO, and PREMARIN Vaginal Cream should not be used under any of the following conditions or circumstances: undiagnosed abnormal genital bleeding; known, suspected, or a history of breast cancer; known or suspected estrogen-dependent neoplasia; active venous thromboembolism or a history of this condition; active or recent arterial thromboembolism; liver dysfunction or disease; in patients with a known hypersensitivity to their ingredients; known or suspected pregnancy.
In a clinical trial, the most commonly reported (≥5%) adverse events for PREMARIN that were statistically different than placebo included vaginal moniliasis, vaginitis, vaginal bleeding, dysmenorrhea, and leg cramps. In a clinical trial, the most commonly reported (≥5%) adverse events for PREMPRO 0.45 mg/1.5 mg and 0.625 mg/2.5 mg that were statistically different than placebo were mastalgia, vaginal bleeding, vaginal moniliasis, leg cramps, dysmenorrhea, breast enlargement, and vaginitis. In a clinical trial, there was no difference in the commonly reported (≥5%) adverse events for women taking PREMPRO 0.3 mg/1.5 mg compared to those taking placebo. In a prospective, randomized, placebo-controlled, double-blind study, the most common adverse reactions (≥5%) for PREMARIN Vaginal Cream are headache, infection, abdominal pain, back pain, accidental injury, and vaginitis.
Please see Prescribing Information, including Boxed Warning, for PREMARIN, PREMPRO, and PREMARIN Vaginal Cream.
The appearance of the PREMARIN tablets is a trademark of Wyeth Pharmaceuticals.
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