WARNING
| 1.
ESTROGENS HAVE BEEN REPORTED TO INCREASE THE RISK
OF ENDOMETRIAL CARCINOMA IN POSTMENOPAUSAL WOMEN:
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 "natural"
estrogens are more or less hazardous than "synthetic"
estrogens at equiestrogenic doses.
2.
ESTROGENS SHOULD NOT BE USED DURING PREGNANCY:
Estrogen therapy during pregnancy is associated
with an increased risk of congenital defects in
the reproductive organs of the fetus, and possibly
other birth defects. Studies of women who received
diethylstilbestrol (DES) during pregnancy have shown
that female offspring have an increased risk of
vaginal adenosis, squamous cell dysplasia of the
uterine cervix, and clear cell vaginal cancer later
in life; male offspring have an increased risk of
urogenital abnormalities and possibly testicular
cancer later in life. The 1985 DES Task Force concluded
that the use of DES during pregnancy is associated
with a subsequent increased risk of breast cancer
in the mothers, although a causal relationship remains
unproven and the observed level of excess risk is
similar to that for a number of other breast cancer
risk factors. There is no indication for estrogen
therapy during pregnancy or during the immediate
postpartum period. Estrogens are ineffective for
the prevention or treatment of threatened or habitual
abortion. Estrogens are not indicated for the prevention
of postpartum breast engorgement. |
DESCRIPTION
Estradiol (17b-estradiol) is
a white, crystalline powder, chemically described as estra-1,3,5(10)-triene-3,17b-diol.
It has an empirical formula of C18H24O2
and molecular weight of 272.37.
Estraderm
The Estraderm system is designed to release 17b-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 a contact surface area of 10 or 20 cm2
contains 4 or 8 mg of estradiol and 0.3 or 0.6 ml of alcohol,
respectively. The composition of the systems per unit
area is identical.
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
film, (2) a drug reservoir of estradiol and alcohol gelled
with hydroxypropyl cellulose, (3) an ethylene-vinyl acetate
copolymer membrane, and (4) an adhesive formulation of
light mineral oil and polyisobutylene. A protective liner
(5) of siliconized polyethylene terephthalate 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.
Climara
Climara, estradiol transdermal system, is designed to
release 17b-estradiol continuously
upon application to intact skin. Four (6.5, 12.5, 18.75,
and and 25.0 cm2) systems are available to
provide nominal in vivo delivery of 0.025, 0.05,
0.075, or or 0.1 mg respectively of estradiol per day.
The period of use is 7 days. Each system has a contact
surface area of either 6.5, 12.5, 18.75, or 25.0 cm2,
and contains 2.04, 3.9, 5.85, or 7.8 mg of estradiol respectively.
The composition of the systems per unit area is identical.
The Climara system comprises two layers. Proceeding from
the visible surface toward the surface attached to the
skin, these layers are a translucent polyethylene film,
and an acrylate adhesive matrix containing estradiol.
A protective liner of siliconized or fluoropolymer-coated
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 17b-estradiol.
The remaining components of the system (acrylate copolymer
adhesive, fatty acid esters, and polyethylene backing)
are pharmacologically inactive.
|
|
