Any drug you take has the possibility of interacting with other drugs, food, or medical conditions. Tamoxifen is a hormonal therapy taken by people with hormone receptor (HR)-positive breast cancer that has a high risk of recurrence (returning) and 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 preventing breast cancer.

There isn’t much information on the impact of tamoxifen drug interactions in breast cancer survivors. However, the findings thus far suggest that tamoxifen might interact with several prescription drugs and over-the-counter (OTC) medications.

How Does Tamoxifen Interact With Other Medications?

Tamoxifen (sold under the brand name Soltamox) may interact with several medications that affect how your liver works.

Tamoxifen is a prodrug — a biologically inactive drug that has to be converted (chemically changed) to its active metabolite. The active metabolite is the form of the drug that produces the beneficial effects. Your liver contains a group of proteins called cytochrome (CY) P450 enzymes that convert tamoxifen to an active metabolite called endoxifen.

In the liver, several CYP450 enzymes help metabolize (process) the medication so that it can be properly used by the body. Tamoxifen is mostly activated by CYP2D6, but other enzymes, such as CYP3A4, may also play a role in converting tamoxifen to endoxifen.

Drugs called CYP2D6 inhibitors and CYP3A4 inhibitors prevent these enzymes from working well and can cause an interaction with tamoxifen. CYP2D6 and CYP3A4 inhibitors keep tamoxifen from being properly metabolized and converted to endoxifen, making the medication less effective.

Although there isn’t much information about the effect of these drug interactions on people, the most likely result is that tamoxifen can’t work as well at preventing breast cancer, leaving you at high risk of recurrent cancer.

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

1. Antidepressants

Some breast cancer survivors experience depression. A recent study suggested that about 20 percent of cancer survivors took an antidepressant.

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

• Selective serotonin reuptake inhibitors such as paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft)
• Serotonin and norepinephrine reuptake inhibitors like duloxetine (Cymbalta)
• Atypical antidepressants such as bupropion (Wellbutrin)

One study found an increase in breast cancer deaths among people who were taking both tamoxifen and paroxetine. However, another study did not find the same association with tamoxifen and fluoxetine. More research is needed to discover why taking antidepressants and tamoxifen might be linked with increased death.

Talk with your doctor about which antidepressant is the best option for you — your mental health is important.

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

• Escitalopram (Lexapro)
• Venlafaxine (Effexor XR)
• Desvenlafaxine (Pristiq)
• Mirtazapine (Remeron)

2. Phentermine

It’s common to gain about 2 to 11 pounds after breast cancer treatment. Some people who want help losing weight might take phentermine (Adipex-P), a prescription medication that reduces appetite. Taking phentermine for a short time, along with following a healthy diet and exercising, can help with weight loss. One MyBCTeam member asked, “Has anyone taken phentermine with tamoxifen?”

There isn’t any clinical research on the effect of taking phentermine and tamoxifen. Phentermine is metabolized in your liver by CYP3A4, but no evidence suggests that it interferes with how well tamoxifen works.

Both phentermine and tamoxifen list QT prolongation, a type of irregular electrical heart activity, as a possible side effect. Although no studies show that this risk is higher if you take the two medications together, it’s important to make sure that every member of your health care team knows if you start taking phentermine.

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.

3. Diphenhydramine

Diphenhydramine (Benadryl) is an 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, which might decrease the effectiveness of tamoxifen.

A MyBCTeam member who was told to avoid diphenhydramine 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, including Tylenol PM Extra Strength, and in sleep medications such as Unisom. It’s important that you check for diphenhydramine among the active ingredients before taking any OTC medication. Talk to your doctor about safer alternatives for your allergy symptoms, such as loratadine (Claritin) or cetirizine (Zyrtec).

4. Aromatase Inhibitors

Like tamoxifen, aromatase inhibitors are used to treat HR-positive breast cancer, especially after menopause. Tamoxifen can decrease the amount of aromatase inhibitors, including anastrozole (Arimidex) and letrozole (Femara), in your bloodstream. Taking tamoxifen with an aromatase inhibitor isn’t recommended because clinical studies haven’t found a benefit of using the combination.

5. Supplements

Supplement use is very common among breast cancer survivors. In one small study, 90 percent of breast cancer survivors took vitamins or supplements. However, some supplements can interact significantly with tamoxifen and other medications.

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

The spice curcumin — also called turmeric — has been claimed to have anticancer effects. However, curcumin may inhibit the enzymes CYP2D6 and CYP3A4. No clinical trials have looked into how taking curcumin along with tamoxifen may affect the likelihood of recurrence, but a small study of 16 breast cancer survivors found that curcumin decreased the level of active endoxifen in the bloodstream.

Another popular supplement, St. John’s wort, is sometimes used for depression and anxiety, as well as hot flashes, which are well-known side effects of tamoxifen. St. John’s wort can affect how your body processes many different drugs, including tamoxifen. There’s some evidence that the herbal supplement can increase how fast your body metabolizes endoxifen, lowering how much is in the blood and making it less effective.

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 using 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

A variety of other medications also can inhibit the CYP2D6 enzyme and might decrease the effectiveness of tamoxifen. These drugs include:

• Heart medications such as verapamil (Verelan), amlodipine (Norvasc), amiodarone (Pacerone), and ticlopidine
• Endocrine medications such as cinacalcet (Sensipar)
• Antipsychotics such as thioridazine, perphenazine, haloperidol, and pimozide (Orap)
• Tricyclic antidepressants such as doxepin (Silenor), amitriptyline, and clomipramine (Anafranil)
• Antibiotics such as rifampin (Rifadin)

Drugs not included in this list might also interact with tamoxifen. Make sure to keep your health care providers up to date about all medications you take, including prescriptions, vitamins, supplements, and OTC medications, and never discontinue any medication by yourself. Your health care team is there to ensure that all your medications work as well as possible — and that none work against each other — to give you the best chance of achieving your hoped-for results.

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 64,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Are you taking tamoxifen? Have you discussed drug and supplement interactions with your breast cancer care team? Share your experiences in the comments below, or start a conversation by posting on your Activities page.