|
| |
Estraderm®
estradiol transdermal system
Continuous delivery for twice-weekly application
See:
Estradiol Evista
Mircette
Activella Alora
Climara Pro
CombiPatch Delestrogen
Esclim
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.
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 cm2 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.
Estradiol USP is a white, crystalline powder, chemically described as
estra-1,3,5 (10)-triene-3,17ß-diol.
The Estraderm system comprises four layers. Proceeding from the visible surface
toward the surface attached to the skin, these layers are (1) a transparent
polyester/ethylene vinyl acetate copolymer film, (2) a drug reservoir of
estradiol USP and alcohol USP gelled with hydroxypropyl cellulose NF, (3) an
ethylene-vinyl acetate copolymer membrane, and (4) an adhesive formulation of
light mineral oil NF and polyisobutylene. A protective liner (5) of siliconized
polyester film is attached to the adhesive surface and must be removed before
the system can be used.
The active component of the system is estradiol. The remaining components of the
system are pharmacologically inactive. Alcohol is also released from the system
during use.
WARNING
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.
|
