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]

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