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Tamoxifen/CYP2D6 Inhibitors

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Certain medications may decrease the effect of tamoxifen by interfering with how the body activates tamoxifen. Amiodarone, thioridazine, and tamoxifen can all affect your heart's rhythm.

What might happen:

Your tamoxifen may not work as well at preventing your breast cancer from returning. Taking amiodarone or thioridazine with tamoxifen may increase your risk of an irregular heartbeat, which may be life-threatening.

What you should do about this interaction:

Let your healthcare professionals (e.g. doctor or pharmacist) know that you are using these products together. Your doctor may want to change your medicine. Let your doctor know right away if you notice an irregular heartbeat or have any dizziness or fainting episodes.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

References:

1.Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 2003 Dec 3; 95(23):1758-64.
2.Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 2005 Jan 5;97(1):30-9.
3.Johnson MD, Zuo H, Lee KH, Trebley JP, Rae JM, Weatherman RV, Desta Z, Flockhart DA, Skaar TC. Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 2004 May;85(2):151-9.
4.Desta Z, Ward BA, Soukhova NV, Flockhart DA. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 2004 Sep;310(3):1062-75.
5.Lim YC, Desta Z, Flockhart DA, Skaar TC. Endoxifen (4-hydroxy-N-desmethyl-tamoxifen) has anti-estrogenic effects in breast cancer cells with potency similar to 4-hydroxy-tamoxifen. Cancer Chemother Pharmacol 2005 May;55(5):471-8.
6.Coller JK, Krebsfaenger N, Klein K, Endrizzi K, Wolbold R, Lang T, Nussler A, Neuhaus P, Zanger UM, Eichelbaum M, Murdter TE. The influence of CYP2B6, CYP2C9 and CYP2D6 genotypes on the formation of the potent antioestrogen Z-4-hydroxy-tamoxifen in human liver. Br J Clin Pharmacol 2002 Aug;54(2):157-67.
7.Dehal SS, Kupfer D. CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res 1997 Aug 15;57(16):3402-6.
8.Goetz MP, Kamal A, Ames MM. Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response. Clin Pharmacol Ther 2008 Jan;83(1):160-6.
9.Beverage JN, Sissung TM, Sion AM, Danesi R, Figg WD. CYP2D6 polymorphisms and the impact on tamoxifen therapy. J Pharm Sci 2007 Sep;96(9):2224-31.
10.Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Weinshilboum RM, Fritcher EG, Nibbe AM, Desta Z, Nguyen A, Flockhart DA. Perez EA, Ingle JN. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 2007 Jan;101(1):113-21.
11.Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Flockhart DA, Desta Z, Perez EA, Ingle JN. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 2005 Dec 20; 23(36):9312-8.
12.Phan MT, Venitz J. Summary minutes of the Advisory Committee Pharmaceutical Science Clinical Pharmacology Subcommittee. Available at: http://www.fda.gov/ohrms/dockets/ac/06/minutes/2006-4248m1.pdf October 18-19, 2006.
13.Rahman NA. Personal communication. Division Director, Office of Clinical Pharmacology, US Food and Drug Administration March 4, 2008.
14.Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Bolander J, Strick R, Beckmann MW, Koelbl H. Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 2009 Oct 7;302(13):1429-36.
15.Onfi (clobazam) US prescribing information. Lundbeck, Inc. December, 2013.
16.Kelly CM, Pritchard KI. CYP2D6 genotype as a marker for benefit of adjuvant tamoxifen in postmenopausal women: lessons learned. J Natl Cancer Inst 2012 Mar 21;104(6):427-8.
17.Regan MM, Leyland-Jones B, Bouzyk M, Pagani O, Tang W, Kammler R, Dell'orto P, Biasi MO, Thurlimann B, Lyng MB, Ditzel HJ, Neven P, Debled M, Maibach R, Price KN, Gelber RD, Coates AS. Goldhirsch A, Rae JM, Viale G,. CYP2D6 genotype and tamoxifen response in postmenopausal women with endocrine-responsive breast cancer: the breast international group 1-98 trial. J Natl Cancer Inst 2012 Mar 21;104(6):441-51.
18.Rae JM, Drury S, Hayes DF, Stearns V, Thibert JN, Haynes BP, Salter J, Sestak I, Cuzick J, Dowsett M. CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst 2012 Mar 21;104(6):452-60.
19.Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, Philippides GJ, Roden DM, Zareba W. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2010 Mar 2;55(9):934-47.

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