Tamoxifen Drug Interactions

Tamoxifen, which is prescribed for the treatment of breast cancer, can interact with some commonly used drugs, including over-the-counter and nutritional supplements. You may be taking tamoxifen for at least five to 10 years, so it's important that you discuss its potential interactions with medications that you are taking now—as well as any new medications that you start to take while you're still taking tamoxifen.

different types of pills that are taken together
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Why Drug Interactions May Occur

Tamoxifen, as well as many other medications, interacts with the CYP2D6 enzyme. This enzyme plays a major role in converting tamoxifen into an active metabolite called endoxifen, which is what makes the drug effective.

Some drugs strongly inhibit the CYP2D6 enzyme, which prevents adequate production of endoxifen from tamoxifen. This would substantially reduce the effects of the drug for you.

What You May Need to Avoid While on Tamoxifen

Some drugs are strong or moderate inhibitors of CYP2D6, while others have a minimal effect on the enzyme. Most doctors recommend that you avoid taking strong and moderate inhibitors of CYP2D6 while you're on tamoxifen.

Medications

Antidepressants are among the medications that can interact with tamoxifen.

  • Selective serotonin uptake inhibitors (SSRIs): Prozac (fluoxetine) and Paxil (paroxetine) are strong inhibitors of CYP2D6, while Luvox (fluvoxamine), Celexa (citalopram), Lexapro (escitalopram), and Zoloft (sertraline) also inhibit the enzyme to some degree.
  • 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)

Other medications that should be avoided with tamoxifen include:

  • 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 and isoniazid
  • Reflux medications: Tagamet (cimetidine)
  • Antifungals: Commonly used for conditions like athlete's foot, tinea versicolor, and toenail fungus, Lamisil or Terbinex (terbinafine) should not be used with tamoxifen.
  • Diabetes medications: Actos (pioglitazone)
  • Parkinson's disease medications: Requip (ropinirole)
  • HIV/AIDS medications: Several
  • Anti-seizure medications: Neurontin (gabapentin)

Supplements

High-dose vitamin E supplements may interact with tamoxifen.

There are no large studies looking at the interaction of herbal supplements with tamoxifen. Supplements that have strong CYP2D6 inhibitory activity in the lab setting include:

  • Skullcap
  • Lemon balm
  • Echinacea
  • Ginseng

In large quantities, green tea extract may increase the level of tamoxifen in the blood, but it hasn't been established whether this is sufficient to cause clinical symptoms.

If you plan on using any herbal supplements, it's important to talk to your oncologist.

QT Prolongation Concern

Tamoxifen's labeling notes that the drug should not be used with drugs that prolong the QT interval. This interval is the amount of time between two of the waves seen on an electrocardiogram (EKG), if significant, it could raise the risk of an abnormal heart rhythm and, could possibly cause sudden death. According to a 2017 review of studies, there is a low risk of clinically significant QT prolongation.

Medications That May Be Used Instead

Information about medication interactions is always growing, and it's important to talk with both your oncologist and pharmacist about any drugs or supplements that you wish to use along with tamoxifen.

Some substitutions that may be recommended for you:

  • Antidepressants: Studies suggest that some of the lesser-degree suppressors may be safe to use with tamoxifen, but research is inconclusive as to whether this might have a clinical effect. Cymbalta (duloxetine) appears to suppress levels of CYP2D6 less than many other antidepressants.
  • Cold medications: 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: You can use Zantac (ranitidine) and others with tamoxifen.

A Word From Verywell

Of note, 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, talk to your oncologist about whether you need supplements or should have your vitamin D level checked.

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Article Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Hansten PD. The Underrated Risks of Tamoxifen Drug Interactions. Eur J Drug Metab Pharmacokinet. 2018;43(5):495-508. doi:10.1007/s13318-018-0475-9

  2. Penn State Health  Milton S. Hershey Medical Center. Vitamin E. Reviewed February 4, 2016.

  3. Teft WA, Gong IY, Dingle B, et al. CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy. Breast Cancer Res Treat. 2013;139(1):95-105. doi:10.1007/s10549-013-2511-4

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