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Tamoxifen and 2d6v6.pub

Drugs that inhibit CYP2D6 that
should be avoided while taking
tamoxifen
Strong CYP2D6 Inhibitors
Generic Names
Brand Names
Moderate CYP2D6 Inhibitors
Generic Names
Brand Names
SSRIs and SNRIs that are not inhibitors
Generic Names
Brand Names
1. Borges S et al. “Quantitative effect of CYP2D6 genotype and in- hibitors on tamoxifen metabolism: Implication for optimization of breast cancer treatment.” Clin Phamacol Ther. 2006 Jul;80(1):61-74. 2. Jin Y et al. “CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment.” J Natl Can-cer Inst. 2005 Jan 5;97(1):30-9. 3. Goetz MP et al. “The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen.” Breast Cancer Res Treat. 2007 Jan;101(1):113-21. 4. Gonzalez-Santiago S et al. “CYP2D6*4 polymorphism as blood predictive biomarker of breast cancer relapse in patients receiving adjuvant tamoxifen.” ASCO Abstract 2007. http://medicine.iupui.edu/clinpharm/ddis/
The information presented on this card is intended as general health information and as an educational tool. It is not intended as medical advice. Only a physician, pharmacist or other health care professional should ad-vise a patient on the use of the medications prescribed. January 2008. Consortium on Breast Cancer Pharmacogenomics The product labeling contains a black box warning for serious and life-threatening events which include uter- Disease Overview – Breast Cancer
ine malignancies, stroke and pulmonary embolism in Breast cancer is the most common and lethal cancer in patient with Ductal Carcinoma in Situ (DCIS) and women. The National Cancer Institute estimates that women at high risk for breast cancer. Data from the in 2007, 178,840 new cases of breast cancer will occur, largest trials conducted indicate that these events oc- and that 40,460 women will die as a result of the dis- cur in 1 in every thousand women over 5 years of ease. The lifetime risk of breast cancer for women in the United States is approximately 1 in 8. Treatment
of breast cancer now involves a number of possible Drug interactions with tamoxifen are important be- drugs that are used after the radiation and chemother- cause the drug is extensively converted to active me- apy that are utilized immediately after surgical re- tabolites (breakdown products) in humans and these moval of the tumor. In women who have estrogen and/ metabolites may be responsible for many of the effects or progesterone receptor positive tumors that include of the drug. Since the main active metabolite is made anti-estrogen therapies including tamoxifen, which is by an enzyme in the liver called cytochrome P450 an antagonist of the action of estrogen in the breast, 2D6 (CYP2D6), drugs that powerfully block the activ- and the aromatase inhibitor class of drugs, which ity of the enzyme may reduce the effects of tamoxifen. lower the estrogen circulating in the body by blocking the synthesis of estrogen by aromatase from andro-gens in fat tissue. The aromatase inhibitors do not work in women before the menopause, in whom most Tamoxifen Metabolism Pathway
estrogen is made in the ovaries, but tamoxifen is effec-tive in both pre-and post-menopausal women. According to the most recent National Cancer Com-prehensive Network breast cancer clinical practice guidelines, risk reduction therapy with tamoxifen, either alone or in conjunction with surgery or radio-therapy, is recommended for premenopausal and post-menopausal patients with estrogen receptor positive disease to prevent breast cancer recurrence. The NIH Breast Cancer Prevention Trial showed that tamoxifen given for 5 years reduces the risk of invasive breast cancer by approximately 50% after 5 years of ta-moxifen therapy. Drug Information - Tamoxifen citrate
(Nolvadex®), originally manufactured by
AstraZeneca (also available as a generic)
Tamoxifen is a medicine that is taken as a pill by mouth.
It is called a selective estrogen receptor modulator
(SERM) because it acts as a weak estrogen in some tis-
sues like bone but as a strong antagonist of the action of
estrogen in the breast. It has been FDA approved for the
We have listed here drugs that are frequently co- treatment of both early and advanced estrogen receptor prescribed with tamoxifen that are powerful inhibitors of positive breast cancer in pre- and post-menopausal the CYP2D6 enzyme that reduce the concentrations of women and in men. Tamoxifen is also FDA approved active metabolites substantially (Strong CYP2D6 Inhibi- for the prevention of breast cancer in women that are at tors), and drugs that are less powerful, but still signifi- cant inhibitors (Moderate CYP2D6 Inhibitors). Since antidepressants are so frequently co-prescribed with tamoxifen (up to 30% of patient in the US) we have spe- • Metastatic breast cancer: 20 to 40 mg daily cifically listed all the SSRI and SNRI antidepressants • Adjuvant treatment for breast cancer: 20 to 40 mg that do not interfere with tamoxifen metabolism as well
• Intraductal carcinoma in situ of breast, following breast surgery and radiation, to reduce risk of invasive disease: 20 mg daily for 5 years • Breast cancer, high-risk; prophylaxis: 20 mg daily for

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