Approved Drug Label (PDF)
4
Contraindications
Additions and/or revisions underlined:
IMVEXXY is contraindicated
in women with any of the following conditions:
Undiagnosed abnormal genital
bleeding [see Warning and Precautions (5.3).
Breast cancer or a
history of breast cancer [see Warnings and Precautions (5.3)].
Estrogen-dependent neoplasia [see Warnings and Precautions (5.3)].
Active DVT, PE, or
history of these conditions [see
Warnings and Precautions (5.2)].
Active arterial
thromboembolic disease (for example,
stroke or MI), or a history
of these conditions [see Warnings
and Precautions (5.2)].
Known
anaphylactic reaction, angioedema, or hypersensitivity to IMVEXXY.
Hepatic impairment or disease.
Protein
C, protein S, or antithrombin deficiency, or other known thrombophilic disorders.
5
Warnings and Precautions
5.10 Exacerbation of
Hypertriglyceridemia
Additions and/or revisions underlined:
In women with
pre-existing hypertriglyceridemia, estrogen therapy
may be associated with elevations of plasma triglycerides leading to pancreatitis. Discontinue
IMVEXXY if pancreatitis occurs.
5.11 Hepatic Impairment and/or
Past History of Cholestatic Jaundice
Additions and/or revisions underlined:
Estrogens may be poorly metabolized
in women with hepatic impairment. Exercise
caution in any
woman with a history of cholestatic jaundice associated
with past estrogen use or with pregnancy. In
the case of recurrence of cholestatic jaundice,
discontinue IMVEXXY.
5.12 Exacerbation
of Hypothyroidism
Additions and/or revisions underlined:
Estrogen administration
leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid
function can compensate for the increased TBG by making more thyroid hormone,
thus maintaining free T4 and T3
serum concentrations in the normal range.
Women dependent on thyroid hormone replacement therapy who
are
also receiving estrogens may require increased doses of their thyroid replacement therapy. Monitor thyroid function
in these women during treatment with
IMVEXXY to maintain their free
thyroid hormone levels in an acceptable range.
5.13 Fluid Retention
Additions and/or revisions underlined:
Estrogens may cause some degree of fluid retention. Monitor any woman with
a condition(s) that might
predispose her to fluid retention, such as cardiac
or renal impairment. Discontinue estrogen-alone therapy, including IMVEXXY, with evidence of medically concerning fluid retention.
5.14
Hypocalcemia
Additions and/or revisions underlined:
Estrogen-induced hypocalcemia may occur in women with hypoparathyroidism. Consider
whether the benefits of estrogen therapy, including IMVEXXY, outweigh the risks
in such women.
5.15
Exacerbation of Endometriosis
Additions and/or revisions underlined:
A few cases of malignant transformation
of residual endometrial implants have been reported in women treated
post-hysterectomy with estrogen-alone
therapy. Consider the addition of progestogen therapy for women
known to have residual endometriosis
post-hysterectomy.
5.16 Hereditary Angioedema
Additions and/or revisions underlined:
Exogenous estrogens may exacerbate symptoms
of
angioedema in women with hereditary angioedema.
Consider whether the benefits of estrogen therapy, including
IMVEXXY, outweigh
the risks in such women.
5.17
Exacerbation of Other Conditions
Additions and/or revisions underlined:
Estrogen therapy,
including IMVEXXY, may cause
an exacerbation of asthma, diabetes
mellitus, epilepsy, migraine, porphyria, systemic lupus
erythematosus, and hepatic
hemangiomas. Consider whether the benefits of estrogen
therapy outweigh the risks in women with these conditions.
5.18
Laboratory Tests
Additions and/or revisions underlined:
Serum follicle stimulating hormone
(FSH) and estradiol levels have
not been shown to be useful
in the management of postmenopausal women with moderate to severe symptoms
of vulvar and vaginal atrophy due to menopause.
5.2 Cardiovascular Disorders
Extensive changes; please refer to label
5.3 Malignant Neoplasms
Additions and/or revisions
underlined:
Endometrial Cancer
An
increased risk of endometrial cancer has been reported with
the use of unopposed estrogen therapy in a woman with a
uterus. The reported endometrial
cancer risk among unopposed
estrogen users is about
2- to 12-fold greater than
in non-users
and
appears dependent
on duration of treatment and on estrogen dose.
Most studies show no significant
increased risk associated with
use of estrogens for less than
1 year. The greatest risk appears associated with prolonged use, with
an increased
risk of 15- to 24-fold for 5 to
10 years or more, and this risk has
been shown to persist for
at least 8 to 15 years after estrogen therapy is discontinued.
Clinical surveillance of all women using estrogen-alone or estrogen plus progestogen
therapy is important. 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.
There
is no evidence that the use of
natural estrogens results in a different endometrial risk profile than synthetic estrogens of
equivalent estrogen dose.
Adding a progestogen to estrogen therapy
in postmenopausal women has
been shown to reduce the risk
of endometrial hyperplasia, which may be
a precursor to endometrial
cancer.
Breast Cancer
The WHI substudy of daily CE (0.625 mg)-alone
provided information about breast cancer in estrogen-alone
users. In the WHI estrogen-alone substudy, after an
average follow-up
of 7.1 years, daily CE-alone
was not associated with an increased
risk of invasive breast cancer [relative risk (RR) 0.80]5 [see Clinical Studies (14.2)].
After a mean follow-up of 5.6 years, the WHI substudy of daily CE
(0.625 mg) plus MPA
(2.5 mg) reported an increased risk of
invasive breast cancer in women who took daily
CE plus MPA compared
to placebo. In this substudy,
prior use of estrogen-alone or estrogen
plus progestin therapy was
reported by 26% of the women. The
relative risk of invasive breast cancer was
1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years,
for CE plus MPA compared with placebo. Among women
who reported prior use of hormone
therapy, the relative risk of invasive breast cancer was
1.86, and the absolute risk was 46 versus
25 cases per 10,000 women-years, for CE plus MPA
compared with placebo.
Among women who reported no prior
use of hormone therapy, the relative
risk of invasive
breast cancer was 1.09, and the
absolute risk was 40 versus 36 cases per 10,000 women-years for CE plus MPA
compared with placebo. In
the same substudy, invasive breast
cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in
the CE (0.625 mg) plus MPA (2.5 mg)
group compared with the placebo
group. Metastatic disease was rare,
with no apparent difference between
the two groups. Other prognostic
factors, such as
histologic subtype, grade and hormone receptor
status did not differ between
the groups6 [see Clinical Studies (14.2)].
Ovarian Cancer
The
CE plus MPA substudy of WHI reported
that estrogen plus progestin increased the risk
of ovarian
cancer. After an average follow-up of 5.6 years,
the relative risk for ovarian
cancer for CE plus
MPA versus placebo was 1.58 (95%
confidence interval
[CI], 0.77 to 3.24), but it was not
statistically significant. The absolute risk for CE plus
MPA versus placebo was 4 versus
3 cases
per 10,000 women-years.7
5.6 Hypercalcemia
Additions and/or revisions underlined:
Estrogen administration
may lead to severe hypercalcemia
in women with breast cancer and bone metastases. Discontinue estrogens, including IMVEXXY, if hypercalcemia occurs and
take appropriate measures
to reduce the serum calcium level.
5.7
Visual Abnormalities
Additions and/or revisions
underlined:
Retinal vascular
thrombosis has been reported
in women
receiving estrogens. Discontinue IMVEXXY
pending examination if there is a sudden partial or complete
loss of vision, or a sudden onset
of proptosis, diplopia, or migraine. Permanently
discontinue estrogens, including
IMVEXXY, if examination
reveals papilledema or retinal vascular
lesions.
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
Risk
Summary
IMVEXXY
is not indicated for use
in pregnancy. There are no data with the use of IMVEXXY
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 developmental and health
benefits of breastfeeding should be
considered along with
the mother’s clinical need for IMVEXXY
and any potential adverse effects on the
breastfed child from IMVEXXY
or from the underlying maternal condition.
8.4
Pediatric Use
Additions and/or revisions underlined:
IMVEXXY is not indicated for use in pediatric
patients. Clinical studies have
not been conducted
in the pediatric population.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
What is the most important
information I should know about IMVEXXY (an estrogen hormone)?
Using estrogen-alone may increase your chance
of getting dementia,
based on a study of women 65 years of age and older.
Do not use estrogens
with progestogens to prevent
heart disease, heart attacks,
strokes or dementia.
Using estrogens with
progestogens may increase your chances of getting heart
attacks, strokes, breast cancer,
or blood clots.
Using estrogens with
progestogens may
increase your chance of getting dementia,
based on a study of women 65 years of age and older.
Only one estrogen-alone product and dose have been shown to increase
your chances of getting
strokes, blood clots, and dementia. Only one estrogen with progestogen product and dose have been shown to increase your chances
of getting heart attacks, strokes,
breast cancer, blood clots, and dementia. Because other products and doses have not been studied
in the same way, it is not known how the use of IMVEXXY
will affect your chances of having these conditions.
Who should not use IMVEXXY?
Do not start using IMVEXXY if you:
Vaginal bleeding
after menopause may be a warning
sign of cancer of the uterus (womb). Your
healthcare provider should check any unusual
vaginal bleeding
to find out the cause.
Before you use IMVEXXY,
tell your healthcare provider about all of your medical conditions, including if you:
have any unusual vaginal bleeding. Vaginal bleeding
after menopause may be a warning sign of cancer
of the uterus (womb). Your healthcare provider should
check any unusual
vaginal bleeding or spotting
to find out the cause.
have any other
medical conditions that may become
worse while you are using IMVEXXY. Your healthcare provider may need to check
you more carefully if you have certain
medical conditions, such as asthma (wheezing), epilepsy (seizures), diabetes, migraine, endometriosis, lupus, angioedema (swelling of face and tongue), problems
with your heart, liver, thyroid, kidneys,
or have high calcium levels
in your blood.
are going to have surgery or will be on bed rest. You may need to stop using IMVEXXY.
are pregnant or think you may be pregnant.
Imvexxy is not for pregnant women.
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