Tamoxifen (Brand Names: Nolvadex, Soltamox)

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Tamoxifen is the oldest and most-prescribed selective estrogen receptor modulator (SERM). Tamoxifen is approved by the U.S. Food and Drug Administration (FDA) to treat:

  • women and men diagnosed with hormone-receptor-positive, early-stage breast cancer after surgery (or possibly chemotherapy and radiation) to reduce the risk of the cancer coming back (recurring)
  • women and men diagnosed with advanced-stage or metastatic hormone-receptor-positive disease

Tamoxifen also is used to:

  • reduce breast cancer risk in women who haven't been diagnosed but are at higher-than-average risk for the disease

Tamoxifen won't work on hormone-receptor-negative breast cancer.

Tamoxifen is available in two forms: a pill taken once a day (brand name: Nolvadex) or a liquid form (brand name: Soltamox). If you dislike pills or you're having trouble swallowing tamoxifen pills, Soltamox can help make it easier to stay on your treatment plan.

Cell with estrogen receptors blocked by tamoxifen and helper proteins
Cell with estrogen receptors blocked by tamoxifen and helper proteins Larger Version

Most doctors recommend taking tamoxifen at the same time each day.

You should not take tamoxifen if you are breastfeeding, pregnant, trying to get pregnant, or if there is any chance that you could be pregnant. Tamoxifen may cause damage to developing embryos. You should use an effective non-hormonal type of birth control — such as condoms, a diaphragm along with spermicide, or a non-hormonal I.U.D. — while you are taking tamoxifen and for 2 months afterward. Ask your doctor which type of non-hormonal birth control would be best for you.

Benefits of tamoxifen

Since its approval in 1998, tamoxifen has been used to treat millions of women and men diagnosed with hormone-receptor-positive breast cancer. While an aromatase inhibitor is the first hormonal therapy medicine choice for postmenopausal women, tamoxifen is the first choice for premenopausal women and is still a good choice for postmenopausal women who can't take an aromatase inhibitor.

Tamoxifen can:

  • reduce the risk of breast cancer coming back by 40% to 50% in postmenopausal women and by 30% to 50% in premenopausal women
  • reduce the risk of a new cancer developing in the other breast by about 50%
  • shrink large, hormone-receptor-positive breast cancers before surgery
  • slow or stop the growth or advanced (metastatic) hormone-receptor-positive breast cancer in both pre- and postmenopausal women
  • lower breast cancer risk in women who have a higher-than-average risk of disease but have not been diagnosed

Tamoxifen offers other health benefits that aren't related to treating cancer. Because it's a SERM, it selectively either blocks or activates estrogen's action on specific cells. While tamoxifen blocks estrogen's action on breast cells, it activates estrogen's action in bone and liver cells. So tamoxifen can:

  • help stop bone loss after menopause
  • lower cholesterol levels

Reasons some people may not get the full benefit of tamoxifen

The body uses an enzyme called CYP2D6 to convert tamoxifen into its active form. Two things can interfere with the body’s ability to make this happen: a flaw in the CYP2D6 enzyme and certain medications that block the effectiveness of this enzyme.

  • Abnormal CYP2D6 enzyme: About 10% of people have a CYP2D6 enzyme that doesn’t function as well as it should. Having an abnormal CYP2D6 enzyme might keep a person from getting the full benefit of tamoxifen. You may want to ask your doctor about being tested for this enzyme abnormality if you are considering taking tamoxifen. Still, CYP2D6 testing is controversial because several large studies found that an abnormal CYP2D6 enzyme didn’t affect tamoxifen’s effectiveness. Together, you and your doctor can decide if CYP2D6 testing makes sense for your unique situation.
  • Medications that can interfere with CYP2D6: There are medications that can block the activity of CYP2D6 to varying degrees (usually stated as “strong” or “moderate” inhibitors of CYP2D6). These medications include some of the antidepressants known as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). There are also other types of commonly prescribed medications, such as Cardioquin (chemical name: quinidine), Benadryl (chemical name: diphenhydramine), and Tagamet (chemical name: cimetidine), that can block CYP2D6. Blocking the activity of CYP2D6 can interfere with the activation of tamoxifen — reducing its effectiveness as an anti-cancer treatment. Most doctors recommend that you avoid taking strong and moderate inhibitors of CYP2D6 while you’re on tamoxifen.

    If you have already finished tamoxifen and you were taking other medications at the same time, make an appointment to talk with your doctor about whether any of your other medications may have interfered with CYP2D6 and the potential benefit you received from tamoxifen. Your doctor may recommend no additional therapy or extended hormonal therapy (with tamoxifen or an aromatase inhibitor) depending on your risk of recurrence, your overall medical condition, and your preferences.

    If you were taking tamoxifen because you are at high risk but have never been diagnosed, and you were also taking a CYP2D6 inhibitor, your doctor may now recommend additional anti-estrogen therapy with tamoxifen or raloxifene (brand name: Evista), depending on your menopausal status. Talk to your doctor about what’s best for your situation.

    If you had progression of breast cancer while on both tamoxifen and a strong or moderate CYP2D6 inhibitor, you can’t assume that tamoxifen failed to work. Rather, it’s possible that tamoxifen never had a fair chance at getting the cancer under control because its action was blocked by the other medicine. Moving forward, tamoxifen, without a CYP2D6 inhibitor, may still provide significant benefit.

For those taking raloxifene (brand name: Evista)

The CYP2D6 enzyme is not needed to activate raloxifene, a sister medicine to tamoxifen used to reduce the risk of developing hormone-receptor-positive breast cancer and treat osteoporosis in postmenopausal women.

Medicines to avoid while taking tamoxifen

In the list below, the medications under the headings “Strong Inhibitors” and “Moderate Inhibitors” can inhibit CYP2D6 and interfere with the effectiveness of tamoxifen. The medications under the heading “Not Inhibitors” do not block the CYP2D6 enzyme and will not interfere with tamoxifen treatment.

This list is incomplete and subject to change over time. Use it as a starting place and ask your doctor if any medications you are taking or that are recommended to you are compatible with tamoxifen.

Strong Inhibitors
Generic Names Brand Names
Bupropion Wellbutrin
Fluoxetine Prozac
Paroxetine Paxil
Quinidine Cardioquin
Thioridazine Mellaril
Perphenazine Trilafon
Pimozide Orap
Clomipramine Anafranil
Ticlopidine Ticlid
Terbinafine Kanusuk
Cinacalcet Sensipar
Moderate Inhibitors
Generic Names Brand Names
Duloxetine Cymbalta
Sertraline Zoloft
Diphenhydramine Benadryl
Amiodarone Cordarone
Trazodone Desyrel
Cimetidine Tagamet
Chlorpromazine Thorazine
SSRIs and SNRIs That Are Not Inhibitors
Generic Names Brand Names
Venlavaxine Effexor
Citalopram Celexa
Escitalopram Lexapro

Source: Coprescription of Tamoxifen and Medications That Inhibit CYP2D6. Kostandinos Sideras, James N. Ingle, Matthew M. Ames, Charles L. Loprinzi, David P. Mrazek, John L. Black, Richard M. Weinshilboum, John R. Hawse, Thomas C. Spelsberg, and Matthew P. Goetz. Journal of Clinical Oncology 2010 28:16, 2768-2776Flockhart.

Side effects of tamoxifen

Tamoxifen's selective estrogen activation effects can cause some serious side effects, including blood clots, stroke, and endometrial cancer. If you and your doctor are considering tamoxifen as part of your treatment plan, tell your doctor if you smoke or have a history of blood clots or heart attack. If you're taking tamoxifen, call your doctor immediately if you have any of these symptoms:

The most common side effects of tamoxifen are:

Hot flashes or night sweats from taking tamoxifen can be troubling. But a 2008 British study suggests that women who experienced hot flashes and night sweats while taking hormonal therapy medicine were less likely to have the breast cancer come back (recur). Knowing that this side effect might indicate a reduced risk of the cancer coming back may help some people stick with treatment despite the side effects.

Some women on tamoxifen have reported memory problems while taking the medicine. While no definitive results are available yet, the ongoing Co-STAR (Cognition in the Study of Tamoxifen and Raloxifene) trial is looking at the effects tamoxifen and raloxifene have on memory and thinking.

How long do I take tamoxifen?

The American Society of Clinical Oncology recommends that:

  • newly diagnosed premenopausal and perimenopausal women take 5 years of tamoxifen as their first hormonal therapy; after this first 5 years is done, the hormonal therapy taken for the second 5 years (for a total of 10 years of hormonal therapy) would be determined by the woman’s menopausal status:
    • postmenopausal women could take another 5 years of tamoxifen or switch to an aromatase inhibitor for 5 years
    • pre- and perimenopausal women would take another 5 years of tamoxifen
  • newly diagnosed postmenopausal women have several options:
    • take tamoxifen for 10 years
    • take an aromatase inhibitor for 5 years; right now there isn’t enough evidence to recommend taking an aromatase inhibitor for 10 years
    • take tamoxifen for 5 years, then switch to an aromatase inhibitor for another 5 years (for a total of 10 years of hormonal therapy)
    • take tamoxifen for 2 to 3 years, then switch to an aromatase inhibitor for another 5 years (for a total of 7 to 8 years of hormonal therapy)
  • postmenopausal women who started taking an aromatase inhibitor but didn’t finish 5 years of treatment can switch to tamoxifen to complete 5 years of hormonal therapy
  • postmenopausal women who started taking tamoxifen but didn’t finish 5 years of treatment can switch to an aromatase inhibitor and take it for 5 years (for a total of 7 to 8 years of hormonal therapy)

Does insurance cover tamoxifen?

While costs vary, tamoxifen is usually less expensive than an aromatase inhibitor because it is a generic medicine. If you have health insurance, check with your insurance company to see if and how much of the cost of tamoxifen is covered. If you don't have health insurance or your insurance doesn't cover the cost of tamoxifen, ask your doctor or nurse about programs in your area that may be able to help.

Soltamox is available to patients who qualify at the same co-pay cost as generic tamoxifen. Patients can download a $10 co-pay per prescription card for unlimited use.

You can also read Breastcancer.org's Paying for Your Care section for information on additional types of financial assistance and cost-lowering tips.

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