Any drug you take has the possibility of interacting with other drugs, food, or medical conditions. This means one substance may change how another works in your body, but not every possible interaction is dangerous or likely to happen.

Tamoxifen is a hormonal therapy taken by people with hormone receptor (HR)-positive breast cancer who have a high risk of recurrence (the cancer coming back). It may also be taken by people who have a high risk of developing breast cancer. It’s usually taken long term, most commonly for five to 10 years.

Drug interactions with tamoxifen might increase the risk of side effects or make tamoxifen less effective at treating breast cancer or lowering the risk of recurrence or development. Research on the real-world effects of tamoxifen drug interactions is limited, and findings have sometimes been mixed.

Here’s what the research so far suggests about prescription drugs and over-the-counter (OTC) medications that might interact with tamoxifen.

How Does Tamoxifen Interact With Other Medications?

Tamoxifen (available as a generic and under the brand name Soltamox) may interact with several medications that affect how your liver breaks down drugs.

Tamoxifen is a prodrug — a drug that has to be converted, or changed, by the body before it can fully work. The active metabolite is the form of the drug that produces the beneficial effects. A metabolite is a substance made when your body breaks down a drug.

Your liver makes proteins called cytochrome P450 (CYP450) enzymes that convert tamoxifen to its active metabolite, endoxifen. CYP450 enzymes help the body process medications. Tamoxifen is mostly activated by an enzyme called CYP2D6, but other enzymes, such as CYP3A4, may also play a role in converting tamoxifen to endoxifen.

Because endoxifen is the active form of tamoxifen, lower endoxifen levels may reduce tamoxifen’s effectiveness. However, studies looking at whether these interactions affect breast cancer outcomes have had mixed results. Researchers aren’t certain whether there’s an impact on long-term cancer outcomes.

If you take tamoxifen and another medication that may interact with it, don’t stop either medication on your own. Instead, talk with your oncologist, pharmacist, or prescribing doctor about the safest option for you.

To avoid tamoxifen drug interactions, make sure to review all your medications and supplements with your oncologist or pharmacist. Knowing about potential interactions can help you have better conversations with your doctors and pharmacist and lower the risk of serious problems.

Some people who’ve had breast cancer experience depression. A 2022 study suggested that about 20 percent of adult cancer survivors take an antidepressant.

The enzyme CYP2D6 can be blocked by some antidepressants, including:

• Strong CYP2D6 inhibitors such as paroxetine and fluoxetine
• Moderate CYP2D6 inhibitors such as bupropion, sertraline, and duloxetine

When possible, many health experts recommend avoiding strong CYP2D6 inhibitors in people taking tamoxifen because these medications can significantly lower endoxifen levels.

One study found an increase in breast cancer deaths among people who were taking both tamoxifen and paroxetine. However, other research hasn’t consistently found that taking antidepressants with tamoxifen worsens breast cancer outcomes.

More recent reviews have found mixed results, meaning the clinical impact of antidepressant interactions with tamoxifen is still being studied.

Even though some antidepressants may interact with tamoxifen, treating depression is important for your mental health and quality of life. Don’t stop taking an antidepressant or tamoxifen without talking with your healthcare team first.

Antidepressants that don’t seem to have interactions with tamoxifen include:

• Escitalopram
• Desvenlafaxine
• Mirtazapine
• Venlafaxine

It’s common to gain about 2 to 11 pounds after breast cancer treatment.

Some people who want help losing weight might take phentermine, a prescription medication that reduces appetite. Taking phentermine for a short time, along with following a healthy diet and getting regular physical activity, can help with weight loss.

One MyBCTeam member asked, “Has anyone taken phentermine with tamoxifen?”

There isn’t clinical research directly studying the effects of taking phentermine and tamoxifen together. Phentermine is metabolized (processed) in your liver by CYP3A4, but there’s no evidence that it affects how tamoxifen is converted to endoxifen or how well tamoxifen works.

Tamoxifen has been associated with irregular electrical heart activity called QT prolongation. Phentermine can affect the heart and blood vessels, and has appeared on lists of medications to avoid in people with long QT syndrome, which causes QT prolongation, and certain types of heart disease. As such, healthcare providers may be cautious about using them together, particularly in people with other risk factors for heart rhythm problems.

Although no studies have directly evaluated taking tamoxifen and phentermine together, your healthcare provider can help weigh the possible benefits and risks based on your health history and other medications.

If you’re interested in losing weight after breast cancer treatment, talk to your doctor about the safest and most effective weight loss options for you.

Diphenhydramine is an OTC antihistamine commonly used in cold, allergy, and sleeping medications.

No clinical trials have looked into how taking diphenhydramine and tamoxifen might affect people, but laboratory studies have shown that diphenhydramine can block CYP2D6. Because CYP2D6 helps convert tamoxifen to endoxifen, there’s a possibility that diphenhydramine could make tamoxifen less effective. However, this possible interaction hasn’t been proven to affect breast cancer outcomes.

One MyBCTeam member was told to avoid diphenhydramine. They shared, “I haven’t been able to sleep for the last three days, and I can’t take Tylenol PM anymore due to the interaction with tamoxifen.”

Diphenhydramine is found in many OTC cold medications and sleep medications. While on tamoxifen, it’s important to check the active ingredients list before taking any OTC medication. Talk to your doctor about safer alternatives for your allergy symptoms, such as loratadine or cetirizine.

Like tamoxifen, aromatase inhibitors are used to treat HR-positive breast cancer, especially in people who’ve gone through menopause. Aromatase inhibitors include anastrozole, letrozole, and exemestane.

Tamoxifen can decrease blood levels of some aromatase inhibitors, including anastrozole and letrozole. Taking tamoxifen with an aromatase inhibitor usually isn’t recommended because clinical studies haven’t found a benefit of using the combination.

In most cases, these medications are used at different times as a part of a breast cancer hormonal therapy treatment plan rather than at the same time.

Many breast cancer survivors take nutritional supplements to try to stay as healthy as possible and feel their best. In one small study, 90 percent of breast cancer survivors reported taking vitamins or supplements.

However, some supplements can interact with tamoxifen and other medications.

St. John’s Wort

St. John’s wort is sometimes used for depression, anxiety, and hot flashes.

St. John’s wort can change how the body processes many medications. It can increase the activity of certain liver enzymes and drug transporters, which may lower levels of tamoxifen’s active metabolites and potentially reduce treatment effectiveness.

Curcumin

“I noticed you take curcumin,” commented one MyBCTeam member to another. “I’m curious if you are on tamoxifen. I worry about its interaction with tamoxifen.”

Curcumin is a substance found in turmeric, a spice. Some people take curcumin supplements because they’ve heard it may have anti-inflammatory or anticancer effects, but more research is needed.

Evidence for curcumin’s interaction with tamoxifen is limited, but it’s worth discussing with your healthcare team. In a small study of 16 people taking tamoxifen for breast cancer, curcumin reduced blood levels of endoxifen. Researchers don’t yet know whether this change affects breast cancer outcomes, but the result suggests it’s wise to be cautious.

Due to a lack of evidence that supplements offer any cancer protection — but do carry a risk of harm — the American Institute for Cancer Research recommends not relying on supplements for cancer prevention. Also, it’s worth noting that the U.S. Food and Drug Administration (FDA) doesn’t regulate supplements as rigorously as it does medications.

Other Drugs That Interact With Tamoxifen

Several other medications may affect how tamoxifen works in your body.

In some cases, these medications can change the amount of tamoxifen’s active form, endoxifen, in your bloodstream. These medications may include:

• Heart medications such as verapamil, amlodipine, amiodarone, and ticlopidine
• Endocrine medications such as cinacalcet
• Antipsychotics such as thioridazine, perphenazine, haloperidol, and pimozide
• Tricyclic antidepressants such as doxepin, amitriptyline, and clomipramine
• Antibiotics, such as rifampin

Not all of these medications affect tamoxifen in the same way, and some interactions are better understood than others. Your doctor or pharmacist can help determine whether a medication you’re taking could affect your tamoxifen treatment.

Make sure to keep your healthcare providers up to date about all medications you take, including prescriptions, vitamins, supplements, and OTC medications, and never stop taking any medication on your own.

Your healthcare team is there to ensure that all your medications work as well as possible — and that none work against each other or raise the risk for other health problems.

Because tamoxifen is often taken for many years, reviewing your medication list regularly can help prevent problems and ensure your breast cancer treatment works as intended.

Join the Conversation

On MyBCTeam, people share their experiences with breast cancer, get advice, and find support from others who understand.

Have you discussed potential drug interactions with tamoxifen with your pharmacist or cancer care team? Let others know in the comments below.