WARNING
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.
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 male and
female fetus, an increased
risk of vaginal adenosis,
squamous cell
dysplasia of the
uterine cervix, and
vaginal cancer in the
female later in life.
The 1985 DES Task Force
concluded that women who used DES
during their pregnancies may subsequently experience an increased
risk of breast
cancer. However, a causal relationship is still unproven, and
the observed level of risk
is similar to that for a number of other breast-cancer risk
factors. There is no indication
for estrogen therapy during pregnancy. Estrogens are ineffective
for the prevention or treatment
of threatened or habitual abortion.
ESTROGENS HAVE BEEN REPORTED TO INCREASE THE RISK OF ENDOMETRIAL
CARCINOMA. Three independent, case-controlled studies have reported
an increased risk of endometrial
cancer in postmenopausal
women exposed to exogenous
estrogens for more than one year.1-3 This risk
was independent of the other known risk
factors for endometrial
cancer. These studies are further supported by the finding that
incidence rates
of endometrial
cancer have increased
sharply since 1969 in eight different areas of the United States
with population-based cancer-reporting systems, an increase which
may be related to the rapidly expanding use of estrogens during
the last decade.4 The three case-controlled studies
reported that the risk
of endometrial cancer in estrogen
users was about 4.5 to 13.9 times greater than in nonusers. The
risk appears to depend
on both duration
of treatment1 and on estrogen dose.3 In view of these
findings, when estrogens are used for the treatment
of menopausal symptoms, the lowest dose
that will control symptoms
should be utilized and medication
should be discontinued as soon as possible. When prolonged treatment
is medically indicated, the patient should be reassessed, on at
least a semiannual basis, to determine the need for continued
therapy. Although the evidence
must be considered preliminary, one study suggests that cyclic
administration
of low doses of estrogen may carry less risk
than continuous administration.3 It therefore appears
prudent to utilize such a regimen. Close clinical
surveillance of all women taking estrogens is important. In all
cases of undiagnosed persistent or recurring abnormal
vaginal bleeding,
adequate diagnostic measures should be undertaken to rule
out malignancy. There is no evidence at present
that "natural" estrogens are more or less hazardous
than "synthetic" estrogens at equiestrogenic doses.
ESTROGENS SHOULD NOT BE USED DURING PREGNANCY. The use of female
sex hormones, both estrogens and progestogens, during early pregnancy
may seriously damage the offspring. It has been shown that females
exposed in utero to diethylstilbestrol, a nonsteroidal estrogen,
have an increased risk
of developing, in later life, a form
of vaginal or cervical
cancer that is ordinarily
extremely rare.5,6 This risk
has been estimated as not greater than 4 per
1,000 exposures.7 Furthermore, a high percentage of
such exposed women (from 30% to 90%) have been found to have vaginal
adenosis,8-12 epithelial changes of the vagina
and cervix. Although these changes are histologically benign,
it is not known whether they are precursors of malignancy. Although
similar data are not available with the use of other estrogens,
it cannot be presumed they would not induce similar changes. Several
reports suggest an association
between intrauterine exposure to female
sex hormones and congenital
anomalies, including congenital heart defects and limb-reduction
defects. 13-16 One case-controlled study 16 estimated a 4.7-fold
increased risk of limb-reduction
defects in infants exposed in utero to sex
hormones (oral contraceptives, hormone
withdrawal tests for pregnancy, or attempted treatment
for threatened abortion). Some of these exposures were very short
and involved only a few days of treatment. The data suggest that
the risk of limb-reduction
defects in exposed fetuses is somewhat less than 1 per
1,000. In the past, female
sex hormones have been
used during pregnancy in an attempt to treat threatened or habitual
abortion. There is considerable evidence
that estrogens are ineffective for these indications, and there
is no evidence from
well-controlled studies that progestogens are effective for these
uses. If Premarin (conjugated estrogens) is used during pregnancy,
or if the patient
becomes pregnant while taking this drug, she should be apprised
of the potential
risks to the fetus, and the advisability of pregnancy continuation.
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DESCRIPTION
Conjugated estrogens is a mixture
of estrogens obtained exclusively from natural
sources, occurring as the sodium
salts of water-soluble estrogen
sulfates blended to represent the average
composition of material derived
from pregnant mares' urine.
It contains estrone, equilin, and 17 a-dihydroequilin,
together with smaller amounts of 17 a-estradiol,
equilenin, and 17 a-dihydroequilenin as salts
of their sulfate esters.
Tablets
Tablets for oral administration
are available in 0.3 mg, 0.625 mg, 0.9 mg, 1.25 mg, and 2.5 mg strengths
of conjugated estrogens.
Premarin Tablets Contain the Following Inactive Ingredients:
Calcium phosphate tribasic, calcium
sulfate anhydrous
(white tablet), calcium sulfate,
carnauba wax, cellulose, glyceryl
monooleate, lactose, magnesium
stearate, methylcellulose, pharmaceutical
glaze, polyethylene glycol,
stearic acid, sucrose, talc, titanium
dioxide.
0.3 mg Tablets Also Contain: D&C yellow
no. 10, FD&C blue no. 1, FD&C blue
no. 2, FD&C yellow no.
6;
0.625 mg Tablets Also Contain: FD&C blue
no. 2, D&C red no. 27, FD&C red
no. 40;
0.9 mg Tablets Also Contain: D&C red
no. 6, D&C red no. 7;
1.25 mg Tablets Also Contain: Black iron
oxide, D&C yellow no. 10, FD&C yellow
no. 6;
2.5 mg Tablets Also Contain: FD&C blue
no. 2, D&C red no. 7.
Injection
Each Secule vial contains 25
mg of conjugated estrogens, in a sterile lyophilized cake which also contains
lactose 200 mg, sodium
citrate 12.2 mg, and simethicone
0.2 mg. The pH is adjusted with
sodium hydroxide
or hydrochloric acid. A sterile
diluent (5 ml) containing
2% benzyl alcohol in sterile
water is provided for reconstitution.
The reconstituted solution is suitable for intravenous
or intramuscular injection.
Vaginal Cream
Each gram of Premarin (conjugated
estrogens) Vaginal Cream contains 0.625 mg conjugated estrogens, in a
nonliquefying base containing
cetyl esters wax, cetyl alcohol, white
wax, glyceryl monostearate,
propylene glycol monostearate, methyl
stearate, benzyl alcohol, sodium
lauryl sulfate, glycerin, and mineral
oil. Premarin Vaginal Cream is applied intravaginally.
CATEGORIES, BRAND NAMES
CATEGORIES: Carcinoma, breast, adjunct; Carcinoma, prostate;
Hypogonadism, female; Kraurosis vulvae; Menopause; Osteoporosis; Ovarian
failure, primary; Vaginitis, atrophic; Pregnancy Category X; FDA Approved
1942 May; Top 200 Drugs
FDA Drug Classes: Antineoplastics; Estrogens
BRAND NAMES:
BRAND NAMES: Ayerogen; Ayerogen Crema Vaginal;
Azumon; C.E.S.; Climarest; Conjugated Estrogens; Conjugen;
Dagynil; Emopremarin; Equin; Femavit; Hyphorin;
Mannest; Menopak-E; Menpoz; Neo-Menovar; Oestro-Feminal;
Ovest; Premaril; Premarin; Premarin Crema V; Premarin
Creme; Premarin Vaginal Creme; Premarina; Premarose;
Presomen; Prevagin-Premaril; Romeda; Sefac;
Srogen; Sukingpo; Transannon
(Foreign Brand names outside U.S. in italics)
FOREIGN BRAND AVAILABILITY:
Ayerogen (Colombia; Venezuela)
Ayerogen Crema Vaginal (Colombia; Ecuador)
C.E.S. (Canada)
Climarest (Germany)
Dagynil (Korea; Netherlands; Taiwan)
Equin (Hong-Kong; Spain)
Femavit (Germany)
Hyphorin (Japan)
Menpoz (Philippines)
Neo-Menovar (Argentina)
Oestro-Feminal (Czech-Republic; Ecuador; Germany; Switzerland)
Premaril (Israel)
Premarin Crema V (Mexico)
Premarin Creme (Australia; New-Zealand; South-Africa)
Premarin Vaginal Creme (Bahamas; Bahrain; Barbados; Belize; Bermuda; Curacao;
Cyprus; Egypt; Guyana; Hong-Kong; Iran; Iraq; Israel; Jamaica; Jordan;
Kuwait; Lebanon; Libya; Malaysia; Netherland-Antilles; Oman; Philippines;
Puerto-Rico; Qatar; Republic-of-Yemen; Saudi-Arabia; Surinam; Syria; Taiwan;
Thailand; Trinidad; United-Arab-Emirates)
Premarina (Sweden)
Premarose (Indonesia)
Presomen (Czech-Republic; Germany)
Prevagin-Premaril (Israel)
Romeda (Japan)
Sefac (Japan)
Srogen (Korea)
Sukingpo (Taiwan)
Transannon (Switzerland)
COST OF THERAPY: $208.05 (Osteoporosis, premenopausal;
Premarin Tablet; .625 mg; 1/day; 365 days)
HCFA JCODE(S): J1410 per
25 mg IV, IM
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