Estraderm?
(estradiol) Transdermal System
Continuous delivery for twice-weekly application
ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER.
Close clinical surveillance of all women taking estrogens is important. 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. There is no evidence that the use of ?natural? estrogens results in a different endometrial risk profile than synthetic estrogens at equivalent estrogen doses. (See WARNINGS, Malignant neoplasms, Endometrial cancer.)
CARDIOVASCULAR AND OTHER RISKS
Estrogens and progestins should not be used for the prevention of cardiovascular disease or dementia. (See WARNINGS, Cardiovascular disorders and Dementia.)
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 (50-79 years of age) during 5 years of treatment with oral conjugated equine estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo (see CLINICAL PHARMACOLOGY, Clinical Studies).
The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated equine estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL PHARMACOLOGY, Clinical Studies).
Other doses of oral conjugated estrogens with 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 and risks for the individual woman.
DRUG DESCRIPTION
Estraderm, estradiol transdermal system, is designed to release estradiol through a rate-limiting membrane continuously upon application to intact skin.
Two systems are available to provide nominal in vivo delivery of 0.05 or 0.1 mg of estradiol per day via skin of average permeability (interindividual variation in skin permeability is approximately 20%). Each corresponding system having an active surface area of 10 or 20 cm? contains 4 or 8 mg of estradiol USP and 0.3 or 0.6 mL of alcohol USP, respectively. The composition of the systems per unit area is identical.
INDICATIONS
Estraderm? (estradiol transdermal system) is indicated in:
* Treatment of moderate to severe vasomotor symptoms associated with the menopause.
* Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with the menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
* Treatment of hypoestrogenism due to hypogonadism, castration, or primary ovarian failure.
* Prevention of postmenopausal osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risks of osteoporosis and non-estrogen medications should be carefully considered.
The mainstays for decreasing the risk of postmenopausal osteoporosis are weight-bearing exercise, adequate calcium and vitamin D intake, and when indicated, pharmacologic therapy. Postmenopausal women require an average of 1500 mg/day of elemental calcium. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake. Vitamin D supplementation of 400-800 IU/day may also be required to ensure adequate daily intake in postmenopausal women.
SIDE EFFECTS
See BOXED WARNINGS, WARNINGS and PRECAUTIONS.
The most commonly reported adverse reaction to Estraderm in clinical trials was redness and irritation at the application site. This occurred in about 17% of the women treated and caused approximately 2% to discontinue therapy. Reports of rash have been rare. There have also been rare reports of severe systemic allergic reactions.
The following additional adverse reactions have been reported with estrogens:
1. Genitourinary system. Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow breakthrough bleeding spotting dysmenorrheal, increase in size of uterine leiomyomata vaginitis, including vaginal candidiasis change in amount of cervical secretion changes in cervical ectropion ovarian cancer endometrial hyperplasia endometrial cancer.
2. Breasts. Tenderness, enlargement, pain, nipple discharge, galactorrhea fibrocystic breast changes breast cancer.
3.
