Pregnancy and Breast-feeding
Warnings [top]
Pregnancy Warning
Tamoxifen caused
fetal harm in
animal studies, including abortions, premature delivery, and death. Because of
the potential for serious adverse effects to the fetus, this drug should not be
used by pregnant women.
Breast-feeding
Warning
No information
is available from
either human or animal studies. However, it is likely that this drug is
excreted in human milk, and because of the potential for serious adverse
effects in nursing infants, you should not take this drug while nursing.
Safety Warnings For This Drug: [top]
FDA BLACK BOX
WARNING
WARNING—For
Women with Ductal
Carcinoma in Situ (DCIS) and Women at High Risk for Breast Cancer: Serious
and life-threatening events associated with NOLVADEX in the risk reduction
setting (women at high risk for cancer and women with DCIS) include uterine
malignancies, stroke, and pulmonary embolism. Incidence rates for these
events were estimated from the NSABP P-1 trial [a major clinical trial
involving tamoxifen1].
Uterine malignancies
[cancers]
consist of both endometrial adenocarcinoma (incidence rate per 1,000
women-years of 2.20 for NOLVADEX vs. 0.71 for placebo) and uterine sarcoma
(incidence rate per 1,000 women-years of 0.17 for NOLVADEX vs. 0.0 for
placebo). For stroke, the incidence rate per 1,000 women-years was 1.43 for
NOLVADEX vs. 1.00 for placebo. For pulmonary embolism, the incidence rate per
1,000 women-years was 0.75 for NOLVADEX vs. 0.25 for placebo.
Some of the strokes,
pulmonary
emboli, and uterine malignancies were fatal.
Health care providers
should
discuss the potential benefits versus the potential risks of these serious
events with women at high risk of breast cancer and women with DCIS
considering NOLVADEX to reduce their risk of developing breast cancer.
The benefits
of NOLVADEX outweigh
its risks in women already diagnosed with breast cancer.2
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Facts About This Drug: [top]
Tamoxifen (NOLVADEX) was
approved by the Food and Drug Adminstration (FDA) in 1977 and is now
approved to be used in several different situations involving breast cancer.3
In 1998, the drug received approval for the reduction in breast cancer
incidence in women at high risk of developing the disease. High risk was defined
as a five-year predicted risk of breast cancer of at least 1.67
percent.
Confusion soon
erupted over whether
the FDA approved tamoxifen for all women 60 years of age and older, without
other risk factors for breast cancer. The news media were initially reporting
that regardless of other factors, all women 60 and older were at a five-year
predicted risk of 1.67 percent (in the high-risk category) for
developing breast cancer and thus were eligible to receive tamoxifen. This is
not the case: Not all women over 60 are at a high risk of developing breast
cancer and not all women over 60 should be receiving tamoxifen to reduce the
risk of breast cancer.
The large clinical
trial (over
13,000 women) that was used to gain approval for tamoxifen in reducing breast
cancer incidence in high-risk women compared tamoxifen to a placebo over a
period of five years.4
The
incidence of breast
cancer was reduced by 2.9 cases per year out
of 1,000 women using tamoxifen.
However, there was an excess of 1.4 cases of endometrial cancer per year out of 1,000 women taking tamoxifen.
{Uterine cancer is more serious than breast
cancer because it is usually diagnosed in an advanced stage--jk.} For blood clot in the lungs, blood clot in the
veins, and stroke, the number of excess cases of these serious adverse drug
reactions with tamoxifen compared to placebo was 0.5, 0.5, and 0.4 cases per year out of 1,000 women
taking tamoxifen, respectively. Overall, there
was an excess of 2.8 cases of a potentially life-threatening adverse drug
reaction per year out of 1,000 women on tamoxifen.
Said another way, for each reduction of one case in
the incidence of breast cancer, there was about one case of a potentially
life-threatening drug reaction with the use of tamoxifen.
In this study,
the benefit of tamoxifen equaled its serious
risks — it was a wash. However, there was also an increased risk of cataracts and cataract surgery in women using tamoxifen.
Side effects
In 2006 there
were three case
reports of women who developed uterine sarcomas during or following treatment
with tamoxifen for breast cancer. Two of these three women died.5
Endometrial cancer,
involving the
lining of the uterus, is the most common form of cancer in this organ,
accounting for approximately 95 percent of all uterine cancers. Uterine
sarcoma is a rare cancer of the body of the uterus, accounting for 2 to 5
percent of all uterine cancers. Because it is usually diagnosed at a more
advanced stage than other uterine tumors, women diagnosed usually have a poorer
outcome and shorter survival than others.
Evidence of the
risk of uterine
sarcoma with tamoxifen use, leading to the FDA’s decision to include a
black-box warning, came in a letter to the New England Journal of Medicine from
FDA staff in June 2002.6
The FDA found that between 1978, when tamoxifen was first approved in the
United States, and April 2001, there were 43 cases of uterine sarcoma reported
to the agency or published in the medical literature. In addition, this cancer
was reported to have developed in 116 women in other countries who had used
tamoxifen for breast cancer.
The Medical Letter
on Drugs and
Therapeutics published a brief article reviewing information on the interaction
of tamoxifen and selective serotonin reuptake inhibitor (SSRI), a class of
drugs used to treat depression. The article summarized the results of two
observational studies on the effect of SSRIs on tamoxifen and the success rate
of tamoxifen in preventing recurrence of breast cancer. One study found a
higher 2-year recurrence rate and the other study found no association of a
recurrence rate.7
Regulatory actions
surrounding
tamoxifen
2002: In June 2002,
the FDA required a black-box warning, the
strongest type of warning that the agency can require, on the professional
product label for the drug. The warning concerns increased risk of sometimes
fatal uterine cancers, stroke, and blood clots in the lungs (pulmonary
embolism) in women at high risk of breast cancer who use the drug to reduce the
incidence of breast cancer and in women with a form of breast cancer called
ductal carcinoma in situ (DCIS). DCIS is characterized by abnormal cells that
involve only the lining of a duct. Such cells have not yet spread outside the
duct to other breast tissues. It is a noninvasive cancer that can become
invasive in some cases.
The June 2002
labeling change was
aimed at women who are considering tamoxifen as a way to reduce the incidence
of breast cancer or those with DCIS for whom a survival benefit of the drug has
not been demonstrated. At this time, the known benefits of tamoxifen outweigh
its risks in women already diagnosed with other kinds of breast cancer.
Before You Use This Drug: [top]
Do not use if
you have or have had:
- blood-clotting problems
- pregnancy or are breast-feeding
- stroke
- uterine malignancies
- pulmonary emboli
- deep vein thrombosis (DVT)
Tell your doctor
if you have or have
had:
- allergy to tamoxifen
- blood disorder
- cataracts or other vision problems
- high cholesterol
Tell your doctor
about any other
drugs you take, including aspirin, herbs,
vitamins, and other nonprescription products. Ask for exams of your eyes8
and for a test to detect endometrial cancer before you start to take tamoxifen.9
When You Use This Drug: [top]
- 8See your doctor regularly for close
monitoring while
taking this drug.
- Continue taking this drug even if
you get an upset
stomach. However, check with your doctor if vomiting occurs shortly after
drug is taken.
- Take analgesics if needed for pain,
which often occurs
when tamoxifen is started but then subsides.
- For women: Tamoxifen may increase
fertility. Do not
become pregnant. Use barrier or nonhormonal contraceptives. Tell your
doctor immediately if you suspect you are pregnant.
How to Use This Drug: [top]
- If you miss a dose, take it as soon
as you remember,
but skip it if it is almost time for the next dose. Do not take double
doses.
- Do not share your medication with
others.
- Take the drug at the same time(s)
each day.
- Store at room temperature with lid
on tightly. Do not
store in the bathroom. Do not expose to heat, moisture, or strong light.
Keep out of reach of children.
Interactions with Other Drugs: [top]
The following
drugs, biologics
(e.g., vaccines, therapeutic antibodies), or foods are listed in Evaluations of
Drug Interactions 2003 as causing “highly clinically significant” or
“clinically significant” interactions when used together with any of the drugs
in this section. In some sections with multiple drugs, the interaction may have
been reported for one but not all drugs in this section, but we include the
interaction because the drugs in this section are similar to one another. We
have also included potentially serious interactions listed in the drug’s
FDA-approved professional package insert or in published medical journal
articles. There may be other drugs, especially those in the families of drugs
listed below, that also will react with this drug to cause severe adverse
effects. Make sure to tell your doctor and pharmacist the drugs you are taking
and tell them if you are taking any of these interacting drugs:
aminoglutethimide,
AVELOX, clopidogrel,
COUMADIN, CYTADREN,10
ESTRADERM, estrogen, moxifloxacin, NORVIR, PLAVIX, PREMARIN, ritonavir,
warfarin.
Adverse Effects: [top]
Call your doctor
immediately if you
experience:
For both women
and men:
- confusion
- blistering, peeling, or loosening
of skin and mucous
membranes
- blurred vision
- yellowing of skin or eyes
- shortness of breath
- swelling or pain in legs
- weakness or sleepiness
- chest pain, anxiety, cough, fainting,
fast heartbeat,
sudden shortness of breath, trouble breathing, dizziness or
lightheadedness
For women:
- pain or pressure in pelvis
- change in vaginal discharge
- bleeding