DRUG INTERACTION WITH TAMOXIFEN

Feb 9, 2010

By Trevor Shewfelt, Pharmacist at the Dauphin Clinic Pharmacy

We now have this and most other articles published in the Parkland Shopper on our Website. Please visit us at www.dcp.ca

The information in this article is intended as a helpful guide only. It is not intended to be used as a substitute for professional advice. If you have any questions about your medications and what is right for you see your doctor, pharmacist or other health care professional.

The TV said my antidepressant is going to give me cancer. Is that true? The best questions in the pharmacy always come from you, the public. After I got a little bit of background information like who the person was, what antidepressant they were on and what they saw on TV, I was able to reassure the person they were going to be okay. But I thought some of the research I had to read to answer the question was interesting.

The excitement all started with a paper published in the Feb 2010 edition of the British Medical Journal. Catherine M Kelly et al. looked at women 66 years old and over treated with tamoxifen for breast cancer at the same time they were taking one SSRI between 1993 and 2005. An SSRI or selective serotonin reuptake inhibitor is a type of antidepressant. The study included 2430 women. What the researchers were looking for was how many women died after their treatment with tamoxifen was over. Then they looked to see if the number of women who died increased if the time the women were on both tamoxifen and an SSRI increased. The answer is yes if a women is on tamoxifen and one type of SSRI called paroxetine or Paxil at the same time during breast cancer treatment, the women is more likely to die after the treatment. And yes, the longer the woman was on both paroxetine and tamoxifen during the cancer treatment, the more likely she is to die after the treatment was over. But, before everyone panics, lets do some pharmacology.

Tamoxifen was originally developed from the bark of the Pacific Yew tree. (See Im not against all natural products). It can be used for different things but most often it is used to prevent or treat breast cancer. Tamoxifen is called a Selective Estrogen Receptor Modulator or SERM. It binds to estrogen receptors in the body and prevents estrogens from having its regular effects. On the negative side, that means it causes hot flashes in women that are very similar to those experienced during menopause. On the positive sign if the women has a tumor in her breast that grows when it is given estrogen, the tamoxifen prevent estrogen from making the tumor grow.

Tamoxifen is also a pro-drug. That means the molecule tamoxifen doesnt actually do anything in the body. It has to be converted to the metabolite endoxifen by an enzyme in the body called cytochrome P450 2D6 (CYP2D6). It is the endoxifen that fights cancer. So if someone didnt have functioning CYP2D6 then tamoxifen wouldnt work for them. Apparently about 7% of us dont have functional CYP2D6 enzymes. So if you give a women without functional CYP2D6 enzymes to treat her breast cancer, it wont help her.

In the BMJ study they looked at SSRIs like paroxetine, because paroxetine stops CYP2D6 from working. Based on the results, the studys authors estimate that if 20 women took paroxetine at the same time as their tamoxifen 41% of the time during breast cancer treatment that one woman more than expected would die from breast cancer at 5 years after treatment. This is an important finding, but remember the study wasnt perfect. It only looked at women over 66 years old. The authors didnt do genetic testing, so they dont know how many patients naturally had CYP2D6 enzymes that didnt work. Were women with more severe breast cancer more depressed, so they got paroxetine more often?

If you are on paroxetine and tamoxifen right now, dont panic. Dont stop taking either drug. At your next appointment, talk to your doctor about options. We can switch the antidepressant to another one that doesnt block CYP2D6. Two options are citalopram and venlafaxine. We can switch your tamoxifen to estrogen blockers that arent prodrugs. The have names like arimidex. These aromatase inhibitors are more potent and expensive than tamoxifen and they arent appropriate for younger women.

As always if you have any questions or concerns about these or other products, ask your pharmacist.

 


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