Tamoxifen

Tamoxifen is a selective estrogen receptor modulator (SERM). It competes with estrogen for the estrogen receptor in breast cells, reducing the estrogen-driven growth signals that some breast cancers depend on. It is not a pure anti-estrogen: it blocks estrogen in the breast but acts mildly like estrogen in the uterus, bone, and blood lipids, which explains several of its risks and benefits.

Tamoxifen is used in adults to:

• treat estrogen receptor-positive metastatic breast cancer in women and men
• treat early-stage estrogen receptor-positive breast cancer after primary treatment (adjuvant therapy), and reduce the chance of cancer developing in the opposite breast
• lower the risk of invasive breast cancer after surgery and radiation for ductal carcinoma in situ (DCIS)
• lower the chance of developing breast cancer in women at high risk, such as those with a strong family history.

Tamoxifen first received FDA approval on December 30, 1977. It is available as a generic.

Take tamoxifen exactly as prescribed and read all medication guides.

• Take it at the same time each day, with or without food
• Measure the oral solution with the supplied dosing cup, not a kitchen spoon
• Treatment usually lasts 5 years. After treatment for early-stage breast cancer, your doctor may recommend up to 10 years. Do not stop early without talking to your doctor
• Check your breasts for lumps monthly, and keep up with your mammograms
• Tell any doctor who treats you that you take tamoxifen, as it can affect some test results

Tamoxifen carries a Boxed Warning for women with ductal carcinoma in situ (DCIS) and women at high risk for breast cancer.

For Women with Ductal Carcinoma in Situ (DCIS) and Women at High Risk for Breast Cancer

When tamoxifen is used to reduce the risk of breast cancer, it has been associated with serious and life-threatening events: uterine cancer (endometrial adenocarcinoma and uterine sarcoma), stroke, and pulmonary embolism, which is a blood clot in the lung. In the NSABP P-1 trial, rates of all of these were higher with tamoxifen than with placebo, and some of the events were fatal.

Women at high risk, and women with DCIS, should discuss these risks against the potential benefit with their doctor before starting tamoxifen to reduce their risk of breast cancer.

In women already diagnosed with breast cancer, the benefits of tamoxifen outweigh its risks.

Do not use tamoxifen if you:

• are pregnant. It can harm an unborn baby. Use effective non-hormonal birth control while taking it and for 2 months after your last dose
• are allergic to it or to any ingredient in the tamoxifen product you are taking

Do not take tamoxifen to lower your breast cancer risk (the high-risk or DCIS setting) if you:

• have had a blood clot in your legs or lungs
• need a coumarin-type blood thinner such as warfarin (Coumadin, Jantoven)
• are otherwise at risk of blood clots, or if your ability to move around is limited for most of your waking hours.

Note: These restrictions apply to risk reduction only. If you are being treated for diagnosed breast cancer, your doctor will weigh them individually.

Before taking tamoxifen, tell your doctor if you have:

• a history of stroke or blood clots
• liver disease
• uterine problems
• irregular periods
• high cholesterol or triglycerides
• cataracts
• low blood counts.

Tell your doctor about every medicine you take, and if you are having chemotherapy or radiation, because chemotherapy with tamoxifen further raises the risk of blood clots.

While taking tamoxifen, you will need regular check-ups, including breast exams and mammograms, annual gynecologic exams, and periodic blood counts and liver function tests.

Pregnancy and contraception

Tamoxifen may harm an unborn baby, including a possible long-term risk of a DES-like (diethylstilbestrol-like) syndrome in a child exposed in the womb. You may need a pregnancy test before starting, and if you are taking tamoxifen for risk reduction, you may need to take your first dose during a period. Tell your doctor straight away if you become pregnant.

Use effective non-hormonal birth control during treatment and for 2 months after your last dose: condoms, a diaphragm or cervical cap with spermicide, a contraceptive sponge, or a plain (non-hormonal) IUD. Avoid hormonal contraception, including birth control pills, injections, implants, patches, hormonal IUDs, and vaginal rings.

Tamoxifen does not cause infertility, even if your periods become irregular or stop.

Breastfeeding

Do not breastfeed while taking tamoxifen or for 3 months after your last dose.

Serious side effects

Get emergency medical help if you have signs of an allergic reaction to tamoxifen: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tamoxifen raises the risk of stroke and blood clots, and clots can occur up to 2 to 3 months after you stop taking it. Call your doctor immediately if you have:

• signs of a stroke, such as sudden numbness or weakness, severe headache, slurred speech, or problems with vision or balance
• signs of a blood clot in the lung, such as chest pain, sudden cough or shortness of breath, dizziness, or coughing up blood
• signs of a blood clot deep in the body, such as pain, swelling, or warmth in one leg.

Also, call your doctor at once if you have:

• unusual vaginal bleeding or discharge, even a small amount
• changes in your menstrual periods, or pain or pressure in your pelvic area
• a new breast lump
• blurred vision, slow clouding of vision, eye pain or redness, or halos around lights
• liver problems, including liver cancer, such as nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-coloured stools, or jaundice
• high blood calcium, such as confusion, tiredness, nausea, vomiting, constipation, increased thirst or urination, or weight loss
• low blood cell counts, such as fever, chills, easy bruising, unusual bleeding, pale skin, or feeling light-headed
• severe upper stomach pain spreading to your back, a possible sign of pancreatitis
• a spreading rash, blistering or peeling skin, or sores in the mouth or eyes.

Common tamoxifen side effects

The most common side effects of tamoxifen include:

• hot flashes
• vaginal discharge, bleeding, or dryness
• irregular or absent periods
• fluid retention, swelling, weight changes
• nausea, tiredness, mood changes
• skin changes, rash, or hair thinning.

Other side effects to be aware of affect:

• Bones. Tamoxifen has been linked to bone loss in the spine and hip in premenopausal women. In postmenopausal women, it slightly increases bone density instead
• Eyes. An increased incidence of cataracts and the need for cataract surgery has been reported
• Uterus. Besides uterine cancer, tamoxifen can cause non-cancerous changes such as thickening of the uterine lining, polyps, endometriosis, and fibroids
• Metastatic disease. Increased bone pain or a temporary disease flare can occur soon after starting, and is sometimes associated with a good response. Tell your doctor, as it can come with high blood calcium
• Men. Loss of libido and impotence have been reported
• Rare reactions. Severe skin reactions, interstitial pneumonitis, angioedema, and raised triglycerides sometimes, with pancreatitis, occasionally appearing more than a year after starting

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adult tamoxifen dose for metastatic breast cancer

• 20 to 40 mg orally daily in women and men. Doses above 20 mg per day should be divided, morning and evening.

Duration: not fixed. Labeling specifies no duration for metastatic disease.

Use: estrogen receptor-positive metastatic breast cancer in adults. In premenopausal women, it is an alternative to oophorectomy or ovarian irradiation.

Adult tamoxifen dose for breast cancer, adjuvant

• 20 mg orally once daily, or 10 mg orally twice daily.

Duration: 5 to 10 years, per the oral solution (Soltamox) labeling. Tablet labeling supports 5 years, noting that continuation beyond 5 years gave no additional benefit in the NSABP B-14 study.

Use: adjuvant treatment of early-stage estrogen receptor-positive breast cancer in adults, and to reduce contralateral breast cancer.

Adult tamoxifen dose for ductal carcinoma in situ (DCIS)

• 20 mg orally daily for 5 years, following breast surgery and radiation, to reduce the risk of invasive breast cancer.

Adult tamoxifen dose to reduce breast cancer incidence in women at high risk

• 20 mg orally daily for 5 years. There are no data supporting use beyond 5 years in this setting.

Use: adult women at least 35 years of age with a 5-year predicted breast cancer risk of 1.67% or greater, as calculated by the Gail Model.

Take it as soon as you remember, but skip it if your next dose is almost due. Do not take two doses at once.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Doses far above those normally prescribed have caused tremor, overactive reflexes, unsteady walking, dizziness, and changes to the heart's electrical rhythm.

Avoid becoming pregnant and avoid hormonal birth control. Otherwise, follow your doctor's instructions about food, drink, and activity.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

• Warfarin and other coumarin blood thinners
• Anastrozole and letrozole
• Rifampin and other strong CYP3A4 inducers, including carbamazepine, phenytoin, phenobarbital and St. John's wort
• Paroxetine and other strong CYP2D6 inhibitors, though the effect on tamoxifen is not well established
• Aminoglutethimide, bromocriptine, and medroxyprogesterone
• Chemotherapy medicines
• Hormonal contraceptives and hormone replacement therapy.

This is not a complete list. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Tablets: store at 20°C to 25°C (68°F to 77°F) in a well-closed, light-resistant container, away from moisture and heat. Do not store in a bathroom.

Oral solution: store at 20°C to 25°C (68°F to 77°F) in the original bottle to protect it from light. Do not refrigerate or freeze. Throw away any unused solution 3 months after you first open the bottle, even if some is left.

Keep tamoxifen and all medicines out of the reach of children. Do not flush unused medicine. Ask your pharmacist about a take-back programme.