Additions and/or
revisions underlined
WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, PROBABLE
DEMENTIA, and BREAST CANCER
Estrogen-Alone Therapy
Endometrial Cancer
There is an increased risk of endometrial cancer in a woman with a
uterus who uses unopposed estrogens. Adding a progestogen to estrogen therapy
has been shown to reduce the risk of endometrial hyperplasia, which may be a
precursor to endometrial cancer. Perform adequate diagnostic measures,
including directed or random endometrial sampling when indicated, to rule
out malignancy in postmenopausal women with undiagnosed persistent or recurring
abnormal genital bleeding [see Warnings and Precautions (5.3)].
Cardiovascular Disorders
and Probable Dementia
The Women’s Health Initiative (WHI) estrogen-alone substudy reported
increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal
women (50 to 79 years of age) during 7.1 years of treatment with daily oral
conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo [see
Warnings and Precautions (5.2), and Clinical Studies (14.2)].
The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI
reported an increased risk of developing probable dementia in postmenopausal
women 65 years of age and older during 5.2 years of treatment with daily CE
(0.625 mg)-alone, relative to placebo. It is unknown whether this finding
applies to younger postmenopausal women [see Warnings and Precautions (5.4),
Use in Specific Populations (8.5), and Clinical Studies (14.3)].
Do not use estrogen-alone therapy for the prevention of cardiovascular
disease or dementia [see Warnings and Precautions (5.2, 5.4), and Clinical
Studies (14.2, 14.3)].
Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy
of the WHI. Therefore, the relevance of the WHI findings regarding adverse
cardiovascular events and dementia to lower CE doses, other routes of
administration, or other estrogen-alone products is not known. Without such
data, it is not possible to definitively exclude these risks or determine
the extent of these risks for other products. Discuss with your patient
the benefits and risks of estrogen-alone therapy, taking into account her
individual risk profile.
Prescribe estrogens with or without progestogens at the lowest
effective doses and for the shortest duration consistent with treatment goals
and risks for the individual woman.
Estrogen Plus Progestin Therapy
Cardiovascular
Disorders and Probable Dementia
The WHI estrogen plus progestin substudy reported increased risks of
pulmonary embolism (PE), DVT, stroke, and myocardial infarction (MI) in
postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with
daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5
mg], relative to placebo [see Warnings and Precautions (5.2), and Clinical
Studies (14.2)].
The WHIMS estrogen plus progestin ancillary study of the WHI reported
an increased risk of developing probable dementia in postmenopausal women 65
years of age and older during 4 years of treatment with daily CE (0.625
mg) combined
with MPA (2.5 mg), relative to placebo. It is unknown whether this finding
applies to younger postmenopausal women [see Warnings and Precautions (5.4),
Use in Specific Populations (8.5), and Clinical Studies (14.3)].
Do not use estrogen plus progestogen therapy for the prevention of
cardiovascular disease or dementia [see Warnings and Precautions (5.2, 5.4),
and Clinical Studies (14.2, 14.3)].
Breast Cancer
The WHI estrogen plus progestin substudy
demonstrated an increased risk of invasive breast cancer [see Warnings and
Precautions (5.3), and Clinical Studies (14.2)].
Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen
plus progestin substudy of the WHI. Therefore, the relevance of the WHI
findings regarding adverse cardiovascular events, dementia and breast cancer to
lower CE plus other MPA doses, other routes of administration, or other
estrogen plus progestogen products is not known. Without such data, it is not
possible to definitively exclude these risks or determine the extent of these
risks for other products. Discuss with your patient the benefits and risks of
estrogen plus progestogen therapy, taking into account her individual risk
profile.
Prescribe estrogens with or without progestogens at the lowest
effective doses and for the shortest duration consistent with treatment goals
and risks for the individual woman.
8.1 Pregnancy
Additions
and/or revisions underlined
Risk
Summary
Vagifem
is not indicated for use in pregnancy. There are no data with the use of
Vagifem in pregnant women; however, epidemiologic studies and
meta-analyses have not found an increased risk of genital or nongenital
birth defects (including cardiac anomalies and limb-reduction defects)
following exposure to combined hormonal contraceptives (estrogens and
progestins) before conception or during early pregnancy.
In
the U.S. general population, the estimated background risk of major birth
defects and miscarriage in clinically recognized pregnancies is 2% to 4% and
15% to 20%, respectively.
8.2 Lactation
Additions
and/or revisions underlined
Risk
Summary
Estrogens
are present in human milk and can reduce milk production in breast-feeding
females. This reduction can occur at any time but is less likely to occur once
breast-feeding is well-established. The clinical need for Vagifem and any
potential adverse effects on the breastfed child from Vagifem or from the
underlying maternal condition.developmental and health benefits of
breastfeeding should be considered along with the mother’s.
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