Tamoxifen Drug Interactions

What Can You and Can't You Take While Using Tamoxifen?

different types of pills that are taken together
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If you have been prescribed tamoxifen for breast cancer, you've likely heard that it can interact with some other medications. Since these interactions involve commonly used drugs and include over-the-counter and nutritional supplements, this is very important. In addition, you will likely be taking the medication for at least 5 to 10 years, making an awareness of possible interactions more than a momentary concern.

Tamoxifen Uses

Tamoxifen has three primary uses:

  • It is most commonly used as adjuvant treatment for women who have early-stage breast cancer that is estrogen receptor positive and who are premenopausal. In this situation, it may reduce the risk of recurrence by 50 percent. It also reduces the likelihood of developing a second cancer in your affected breast (if you had a lumpectomy) or in your other breast.
  • Tamoxifen is used for both women and men who have metastatic breast cancer that is estrogen receptor positive and who are not resistant to the drug.
  • Tamoxifen may also be used as a preventive therapy in women who have an elevated risk of developing breast cancer. In this setting, it can reduce a women's risk of developing breast cancer by half.

The most common dosage is 20 mg daily for 5 to 10 years. (Those who become postmenopausal or have received ovarian suppression therapy may be switched over to an aromatase inhibitor instead).

Why Drug Interactions May Occur

The reason that understanding the metabolism of tamoxifen is important is that there are many other medications that similarly affect the CYP2D6 enzyme. Some drugs strongly inhibit the enzyme so that little if any endoxifen is produced when they are taken with tamoxifen. In essence, it would be like you didn't take the drug at all.

Medications that affect this enzyme include those commonly used in women with breast cancer such as many antidepressants and even common cold and allergy remedies.

The information on these interactions is relatively new (tamoxifen was approved in 1998, but interactions were not noted until later on) and studies are currently in progress looking at this issue in greater depth. Of note, is that recent research has found that your vitamin D level may be linked to the effectiveness of tamoxifen and that levels of endoxifen tend to be significantly higher in women in the summer months. Since there have been studies suggesting that vitamin D may help fight breast cancer, have your oncologist check your vitamin D level if you have not yet had this done.

Potential Drug Interactions With Tamoxifen

Below we list a number of medications that may interact with tamoxifen. Of note is that these drugs may reduce the effectiveness of tamoxifen but do so to different degrees. Some drugs are very strong inhibitors of CYP2D6, whereas others inhibit the enzyme to lesser degrees. This list is not exhaustive and other less commonly used medications may interact with tamoxifen as well.

Medications that should be avoided with tamoxifen include:

  • Selective serotonin uptake inhibitors (SSRIs): Prozac (fluoxetine) and Paxil (paroxetine) are strong inhibitors of CYP2D6. Luvox (fluvoxamine), Celexa (citalopram), Lexapro (escitalopram). and Zoloft (sertraline) also inhibit the enzyme to some degree. It is likely that this interaction is responsible for the increased risk of death found in women taking Paxil.
  • Selective serotonin/norepinephrine reuptake inhibitors (SNRIs): Effexor (venlafaxine), Pristiq (desvenlafaxine)
  • Wellbutrin and Zyban (bupropion): Used for depression and smoking cessation
  • Tricyclic antidepressants: Anafranil (clomipramine) and Norpramin (desipramine)
  • Endocrine medications: Sensipar (cinacalcet), Parlodel (bromocriptine), and Parnate (tranlcypromine)
  • Typical antipsychotics such as Mellaril (thioridazine), Trilafon (perphenazine), Orap (pimozide), and Thorazine (chlorpromazine), and atypical antipsychotics such as Risperdal (risperidone), Clozaril (clozapine), Geodon (ziprasidone), and Seroquel (quetiapine)
  • Cardiac medications: Cardioquin (quinidine),Ticlid (ticlopidine), Cardene (nicardipine)
  • Antihistamines: Benadryl (diphenhydramine)
  • Antibiotics: Rifampin can greatly reduce tamoxifen levels, isoniazid (used for TB).
  • Reflux medications: Tagamet (cimetidine)
  • Antifungals: Commonly used for conditions like athlete's foot, tinea versicolor, and toenail fungus, the drug Lamisil or Terbinex (terbinafine) should not be used with tamoxifen, though it is not included on many of the lists of drugs to avoid.
  • Diabetes medications: Actos (proglitazone)
  • Parkinson's disease medications: Requip (ropinirole)
  • HIV/AIDS medications: Several
  • Anti-seizure medications: Neurontin (gabapentin)
  • Vitamins: High dose vitamin E supplements may interact with tamoxifen
  • Nutritional supplements: There are no large studies looking at the interaction of herbal supplements with tamoxifen. Supplements that have strong CYP2D6 inhibitory activity in the lab include skullcap, lemon balm, echinacea, and ginseng. In large quantities, green tea extract may increase the level of tamoxifen in the blood, but this is probably not sufficient to cause clinical symptoms. If you plan on using any herbal supplements it's important to talk to your oncologist.

    Alternatives: Medications That May Be Used Instead

    There are drugs that you probably can take if you are using tamoxifen. Here's what to know:

    • Antidepressants vary in the degree to which they affect the enzyme CYP2D6. Cymbalta (duloxetine) appears to suppress levels of CYP2D6 less than many other antidepressants. The medications listed above under "drugs to avoid" differ significantly in the degree to which they suppress the enzyme. Recent studies suggest that some of the lesser degree suppressors may be safe to use with tamoxifen, but studies at this time are inconclusive as to whether this might have a clinical effect as well.
    • Many cold medications contain more than one ingredient, so it's important to read labels. A large number of over-the-counter preparations for colds and flu contain Benadryl. Allergy drugs such as Zyrtec and Claritin are thought to be safe to use with tamoxifen.
    • Acid reflux medications that are likely okay include Zantac (ranitidine) and others.

    We are always learning more about medication interactions and it's important to talk with both your oncologist and pharmacist about any drugs that you wish to use along with tamoxifen.

    QT Prolongation

    If you've looked at your package labeling you may have noted that tamoxifen should not be used with other medications that prolong the QT interval. The QT interval refers to the amount of time between two of the waves seen on an electrocardiogram. It's thought that if the QT interval is prolonged significantly, it raises the risk of an abnormal heart rhythm, and possibly, sudden death.

    The packaging information warns that tamoxifen may result in QT prolongation when used along with other drugs that can cause QT prolongation. A 2017 review of studies, however, claims that there is likely to be a low risk of clinically significant QT prolongation in this setting, especially at only 20 mg daily.

    A Word From Verywell

    It's very important to talk to your oncologist and pharmacist about any pharmaceutical medication, over-the-counter medication, or dietary supplement you are considering while you are on tamoxifen. Of note is that there may be times in which the benefits of using one of these drugs may outweigh the risk of reducing your endoxifen levels. Having an awareness, however, can help you ask your doctor the right questions.

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