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Tamoxifen side effects and how to avoid them

Tamoxifen side effects include weight gain, pain, and mood disturbances
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By | Sep. 6, 2022 Medically reviewed by Josephine Bawab, Pharm.D.

Common tamoxifen side effects | Serious side effects | Weight gain | Pain | Mood disturbances | Side effects timeline | Contraindications | Warnings | Interactions | How to avoid side effects | How to treat side effects

Tamoxifen is a generic prescription drug used for hormone receptor-positive breast cancer treatment or breast cancer prevention in people with a high risk of breast cancer. Also prescribed as brand-name Soltamox or Nolvadex, tamoxifen is used to treat metastatic breast cancer, breast cancer that has spread to the lymph nodes in postmenopausal women, and early-stage breast cancer (ductal carcinoma in situ or DCIS) to prevent it from developing into invasive cancer. 

Tamoxifen is a selective estrogen receptor modulator (SERM). It blocks the effects of estrogen, the female hormone that promotes tumor growth in HER+ breast cancers. Like many anticancer drugs, tamoxifen is a powerful drug with a long list of side effects. Fortunately, most of its side effects will be mild.

Common side effects of tamoxifen

The most commonly experienced side effects of tamoxifen are as follows:

  • Hot flashes
  • Flushing
  • Fluid retention
  • Joint pain
  • Mood disturbances
  • Arthritis
  • Nausea
  • Menstrual changes, menstrual period delays, or absence of menstruation
  • Weight loss
  • Vaginal bleeding
  • Tiredness
  • Sore throat
  • Infection
  • Skin rash
  • Vomiting
  • Depression
  • Vaginal discharge
  • Elevated blood pressure
  • Swelling of the hands, feet, and lower legs
  • Back pain
  • Weight gain
  • Abdominal pain
  • Insomnia
  • Cough
  • Headache
  • Dizziness
  • Cataracts
  • Constipation
  • Trouble breathing
  • Diarrhea

Serious side effects of tamoxifen

The most serious side effects of tamoxifen include:

  • Blood clots
  • Stroke
  • New malignancies
  • Endometrial cancer
  • Ovarian cysts
  • Death or spontaneous abortion of a fetus
  • Birth defects
  • Cataracts
  • Damage to the retina
  • Liver dysfunction
  • Lowered white blood cell or platelet counts
  • High blood calcium
  • Pancreas problems
  • Severe allergic reactions

Weight gain

Weight gain may be a possible side effect of tamoxifen. In clinical trials, weight gain was only a significant problem when tamoxifen was taken for early-stage breast cancer. In that trial, 9% of participants gained weight over several years of treatment. However, in clinical trials in which tamoxifen was used with other drugs to treat later-stage breast cancer, 23% of participants experienced weight loss. If any unintended weight changes are experienced in that time, talk to the prescribing healthcare provider for medical advice.

Pain

Pain is a common side effect of tamoxifen. In all the initial clinical trials, a variety of pains were reported: headache, joint pain, bone pain, muscle pain, abdominal cramps, chest pain, breast pain, and generalized pain. The alternative to tamoxifen is to take an aromatase inhibitor (AI) such as Arimidex (anastrozole) or Femara (letrozole), but these medications have a higher incidence of pain as a side effect. If pain is a problem, talk with the prescriber about pain management options.

Mood disturbances

It would make sense that tamoxifen might cause mood changes because many of its side effects are similar to menopause symptoms, such as hot flashes, flushing, and night sweats. However, mood disturbances may or may not be a side effect of tamoxifen. In clinical trials, mood problems were only reported in one trial using tamoxifen to treat early-stage breast cancer. Mood disturbances were not a significant problem in all other tamoxifen trials. In addition, one later study followed almost 500 women taking tamoxifen over five years and found no problems with mood disturbances. Mood disturbances are always a possibility with or without drug treatment. It’s possible that mood problems may be due to tamoxifen treatment, but it’s also possible they’re not. If they’re experienced, talk to the prescriber about options for managing them.

How soon do tamoxifen side effects start?

Like all prescription drugs, many of tamoxifen’s side effects can start early in treatment. Some, like flushing, can start even after the first dose. It takes about four weeks of continual daily dosing for tamoxifen to reach steady-state levels in the body, so it’s normal to start experiencing side effects by that time.

How long do tamoxifen side effects last?

Some side effects will improve over time as the body adapts to the drug. Unfortunately, estrogen-blocking cancer treatment is usually a long-term therapy, so the drug’s side effects may become a part of everyday life. Guidelines call for tamoxifen treatment to continue for three, five, or 10 years to prevent breast cancer from recurring. Long-term treatment substantially reduces the risk of future breast cancer or death. As long as the side effects aren’t too serious, healthcare professionals will want their patients to continue with tamoxifen treatment. Guidelines also call for tamoxifen therapy, if it’s used for three or five years, to be followed by five to seven years using a different estrogen-blocking therapy, an aromatase inhibitor. These drugs, too, will cause side effects. Most side effects of estrogen-blocking therapy will resolve when treatment ends.

What are the long-term side effects of tamoxifen?

Tamoxifen is a long-term drug treatment. Daily dosing could last for a decade. Delayed side effects, such as menstruation irregularities, new cancers, blood clots, or vision problems, usually take a few weeks or months of treatment to occur, but they can happen at any time during the years-long treatment. The length of treatment does not add any new side effects or significantly increase the risk of other side effects. According to the largest study of tamoxifen treatment, ATLAS, the risk of many of the most severe side effects of tamoxifen only goes up slightly if tamoxifen is taken for 10 years, rather than five years.

Tamoxifen contraindications

Tamoxifen is contraindicated in anyone with the following medical conditions:

  • A history of blood clot problems
  • Pregnancy
  • Undiagnosed vaginal bleeding
  • A known allergy to the drug

Pregnancy

Tamoxifen can cause birth defects, kill a fetus, or cause a spontaneous abortion. It is never used in pregnant women. Healthcare professionals will urge women of reproductive age to use nonhormonal contraception and to be tested for pregnancy.

Breastfeeding

Because of the risk to a nursing infant, women should not breastfeed when taking tamoxifen. Breastfeeding should not be resumed until tamoxifen has been discontinued for at least three months.

Children

The Food and Drug Administration (FDA) has not approved tamoxifen to treat children or adolescents. However, some healthcare providers have prescribed tamoxifen to young girls (2–10 years of age) to treat the early onset of puberty. This is not common, though, because there are effective, well-studied, FDA-approved puberty blockers that can be used instead.

Older adults

In one clinical trial, tamoxifen was found to be effective in older women without any increased risk of side effects relative to younger adults.

Tamoxifen warnings

Most cancer drugs come with a host of warnings. However, tamoxifen does not attack or kill the cancer cells. It simply blocks the female hormone, estrogen. Therefore, there are fewer hazards with tamoxifen than with other cancer drugs.

Cautions

A few medical conditions will require caution or extra monitoring: 

  • People at risk for blood clots will need closer monitoring because tamoxifen is associated with potentially hazardous blood clots.
  • People with high fats or high cholesterol may have their condition worsened when taking tamoxifen.
  • People with cataracts or vision problems might have their condition worsened by tamoxifen.
  • Women of reproductive age will need to use nonhormonal contraception to prevent pregnancy. 
  • People whose cancer has spread to the bones may be at a higher risk for a tumor flare accompanied by high calcium levels in the body.
  • Some people do not break down tamoxifen very well, so doses may need to be adjusted.

Abuse and dependence

Tamoxifen is not associated with drug abuse and does not cause physical dependence or withdrawal. 

Overdose

Get medical attention or call a poison control center if too much tamoxifen is taken. The maximum daily dose approved by the FDA is 20 mg, but the maximum off-label daily dose is 120 mg. Extremely large doses have been known to cause neurological problems such as tremors, heightened reflexes, and even seizures.

Tamoxifen interactions

Some drugs can cause problems when combined with tamoxifen. They are:

  • Anticoagulants: Tamoxifen can increase the effects of anticoagulants, making bleeding episodes more likely. In particular, warfarin is never used when tamoxifen is prescribed for breast cancer prevention.
  • Aromatase inhibitors: AIs are also used to block estrogen in women with hormone receptor-positive breast cancer. They block the ability of the body to produce estrogen. They are not supposed to be used at the same time as tamoxifen, but years of AI treatment typically follow tamoxifen treatment.

Some tamoxifen drug interactions increase the risk of heart rhythm abnormalities. These drugs include:

Some drugs speed up the body’s metabolism of tamoxifen, causing tamoxifen levels in the body to fall quickly and making treatment less effective. These include:

How to avoid tamoxifen side effects

Tamoxifen is taken for years, so learning how to avoid side effects is essential. Everyone may experience a different set of side effects and can find different ways to avoid them. When starting the drug, though, start with the following:

1. Make sure the prescriber has a complete medical history

This is standard advice for anyone prescribed a drug. It’s one of the surest ways to avoid serious side effects. It’s safe to say, however, that an oncology specialist will obtain a thorough medical history and perform many tests before starting treatment. The oncologist will particularly pay attention to:

  • Any history of blood clot problems
  • Liver disease
  • Cataracts or other vision problems
  • High fats or high cholesterol
  • Pregnancy or pregnancy plans
  • Breastfeeding or breastfeeding plans

2. Take tamoxifen as instructed

Follow all the instructions for the medication given by the prescriber or written on the prescription label. Take doses as scheduled, and don’t miss any doses.

3. Cut back on smoking, alcohol, and hot drinks

Avoiding nicotine, alcohol, and hot drinks can help reduce the severity of hot flashes.

4. Have regular eye exams

Schedule regular eye exams to catch possible vision problems before they become serious.

5. Eat a healthy diet

To avoid weight changes and bone loss, eat a healthy diet. The prescriber or a nutritionist should be able to help.

How to treat side effects of tamoxifen

About 20% to 50% of women with HER+ breast cancer stop hormone therapy because of the adverse effects. Managing side effects is important for the long-term success of the treatment. Here’s some advice:

Hot flashes

Dress in layers and remove clothes when you get too hot. Cooling pads, cold drinks, and spraying the face with cool water can also help. If hot flashes are too burdensome, talk to the prescribing healthcare provider. Some antidepressants, particularly SSRIs or SNRIs, can help reduce hot flashes.

Swelling

To help reduce swelling, elevate the feet. If swelling persists or gets worse, let the prescribing healthcare provider know about it.

Skin rash

A skin rash may be the first sign of a potentially severe drug reaction, so tell the prescribing healthcare provider about it immediately. If it’s a severe rash, go to an emergency room.

Problems with vision

Immediately contact the prescribing healthcare provider at any sign of vision changes, such as blurred vision, halos around lights, or reduced night vision.

Vaginal bleeding or discharge

Abnormal vaginal bleeding or unusual discharge may be a sign of a serious problem such as uterine cancer. Immediately contact the prescribing healthcare provider.

Blood clots

Blood clots can’t be seen, but they can cause health-threatening medical conditions such as a deep vein thrombosis or pulmonary embolism. Get immediate medical attention at any symptom of a possible blood clot, including:

  • Leg pain
  • Leg swelling or redness
  • Chest pain
  • Coughing up blood
  • Shortness of breath

Tumor flare-up

Tamoxifen can cause breast cancer that has spread to the bones to flare up and serum calcium levels to increase. Immediately contact the prescribing healthcare provider when any of these symptoms are noticed:

  • Bone pain
  • Malaise
  • Constipation
  • Confusion

Liver problems

Tamoxifen can affect liver function, so tell the prescriber if symptoms of liver problems are noticed, such as:

  • Dark urine
  • Pale stools
  • Throwing up
  • Loss of appetite
  • Bleeding and bruising
  • Yellowing of the skin or eyes

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