Tamoxifen Drug Interactions

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. And since you will likely be taking the medication for at least five to 10 years, awareness of possible interactions is more than a momentary concern.

Why Drug Interactions May Occur

The reason that understanding the metabolism of tamoxifen is important is that there are many other medications (as well as supplements) that similarly affect the CYP2D6 enzyme. This enzyme is the most important one involved in breaking tamoxifen down into a metabolite called endoxifen, which is what makes the drug effective.

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.

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.

What You May Need to Avoid While on Tamoxifen

Below are a number of medications and supplements that may interact with tamoxifen. Of note is the variation in the extent to which these may reduce the effectiveness of tamoxifen; some are very strong inhibitors of CYP2D6, whereas others inhibit the enzyme to lesser degrees. This list is not exhaustive and other less commonly used options may interact with tamoxifen as well.

There may be times when the benefits of using one of these options may outweigh the risk of reducing your endoxifen levels. This, however, should be decided in consult with your physician.

Medications

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 and tamoxifen.
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 can also be problematic.
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 (proglitazone)
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 include:

Skullcap
Lemon balm
Echinacea
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.

QT Prolongation Concern

Tamoxifen's labeling notes that the drug should not be used with others that prolong the QT interval. This (the amount of time between two of the waves seen on an electrocardiogram), if significant, is said to raise the risk of an abnormal heart rhythm and, possibly, sudden death. 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.

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.

If you are on any of the above, there are 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 as well. 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 that are likely OK include Zantac (ranitidine) and others.

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, have your oncologist check your vitamin D level if you have not yet had this done.