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Alora®
(estradiol transdermal system)
Continuous Delivery for Twice Weekly Dosing
See:
Estradiol Evista
Mircette
Activella Climara Pro
CombiPatch Delestrogen
Esclim Estraderm
Estring Estrace Tablets
Evamist Vagifem Vivelle-Dot
All of these products are used to reduce symptoms
of menopause, including feelings of warmth in the face, neck, and chest; the
sudden intense episodes of heat and sweating known as "hot flashes"; dry, itchy
external genitals; and vaginal irritation. They are also prescribed for other
conditions that cause low levels of estrogen, and some doctors prescribe them
for teenagers who fail to mature at the usual rate.
Along with diet, calcium supplements, and exercise, Alora, Estraderm, Climara,
Vivelle, and Vivelle-Dot are prescribed to prevent osteoporosis, a condition in
which the bones become brittle and easily broken.
PRESCRIBING INFORMATION
Alora (estradiol transdermal system) is designed to deliver estradiol
continuously and consistently over a 3 or 4-day interval upon application to
intact skin. Four strengths of Alora are available, having nominal in vivo
delivery rates of 0.025, 0.05, 0.075, and 0.1 mg estradiol per day through skin
of average permeability (inter-individual variation in skin permeability is
approximately 20%). Alora has contact surface areas of 9, 18, 27, and 36 cm2 and
contains 0.77, 1.5, 2.3, and 3.1 mg of estradiol, USP, respectively. The
composition of the estradiol transdermal systems per unit area is identical.
Estradiol, USP is a white, crystalline powder that is chemically described as
estra-1,3,5(10)-triene-3, 17β-diol, has an empirical formula of C18H24O2 and has
molecular weight of 272.39.
Alora consists of three layers. Proceeding from the polyethylene backing film as
shown in the cross-sectional view below, the adhesive matrix drug reservoir that
is in contact with the skin consists of estradiol, USP and sorbitan monooleate
dissolved in an acrylic adhesive matrix. The polyester overlapped release liner
protects the adhesive matrix during storage and is removed prior to application
of the system to the skin.
WARNINGS
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 currently no evidence that the use
of "natural" estrogens results in a different endometrial risk profile than
synthetic estrogens of equivalent estrogen dose. (See WARNINGS, Malignant
neoplasms, Endometrial cancer)
CARDIOVASCULAR AND OTHER RISKS
Estrogens with and without 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 to 79 years of age) during 5 years of
treatment with oral conjugated estrogens (CE 0.625mg) combined with
medroxyprogesterone acetate (MPA 2.5mg) relative to placebo (See CLINICAL
PHARMACOLOGY, Clinical Studies and WARNINGS, Cardiovascular disorders and
Malignant neoplasms, Breast cancer)
The Women's Health Initiative Memory Study (WHIMS), a substudy of WHI, reported
increased risk of developing probably dementia in postmenopausal women 65 years
of age or older during 4 years of treatment with oral conjugated estrogens plus
medroxyprogesterone acetate relative to placebo. It is unknown whether this
finding applies to younger postmenopausal women . (See CLINICAL PHARMACOLOGY,
Clinical Studies and WARNINGS, Dementia and PRECAUTIONS, Geriatric Use )
Other does 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.
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