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Michaela J. Higgins, James M. Rae, David A. Flockhart, Daniel F. Hayes and Vered Stearns

Pharmacol Exp Ther 2006 ; 318 : 503 – 512 . 9 Borges S Desta Z Li L . Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment . Clin Pharmacol Ther 2006 ; 80 : 61

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Kostandinos Sideras and Charles L. Loprinzi

effective and better tolerated than higher doses. An increase to 20 mg/d can be considered. Paroxetine, being a potent inhibitor of CYP2D6, should not be used in women with tamoxifen, as will be discussed later. Fluoxetine Two randomized controlled

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Andrea M. Trescot

The analgesic activity from codeine is believed to occur from metabolism of codeine to morphine by CYP2D6, and therefore codeine is susceptible to drug–drug interactions, as well as the genetic influences discussed previously. This includes the

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Wendy ab MD Anderson Benjamin O. bc MD Edge Stephen B. d MD Robinson Kerrin G. MA 2 2009 7 7 2 2 193 193 201 201 10.6004/jnccn.2009.0013 Pharmacogenetics of Tamoxifen: Who Should Undergo CYP2D6 Genetic Testing? Higgins

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predictor of breast cancer outcomes; however, several emerging biomarkers, such as the CYP 2D6 genotype to determine tamoxifen (Soltamox, AstraZeneca Pharmaceuticals, LP) efficacy, are also being researched extensively. “The efficacy of tamoxifen therapy

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Robert Swarm, Amy Pickar Abernethy, Doralina L. Anghelescu, Costantino Benedetti, Craig D. Blinderman, Barry Boston, Charles Cleeland, Nessa Coyle, Oscar A. deLeon-Casasola, June G. Eilers, Betty Ferrell, Nora A. Janjan, Sloan Beth Karver, Michael H. Levy, Maureen Lynch, Natalie Moryl, Barbara A. Murphy, Suzanne A. Nesbit, Linda Oakes, Eugenie A. Obbens, Judith A. Paice, Michael W. Rabow, Karen L. Syrjala, Susan Urba and Sharon M. Weinstein

hepatic enzyme, CYP2D6. 29 , 30 Because data suggest that CYP2D6-inhibiting antidepressants increase risk of recurrence in patients with breast cancer treated with tamoxifen 31 , 32 (see Additional Therapies, page 1082), it is reasonable to assume that

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Robert A. Swarm, Amy Pickar Abernethy, Doralina L. Anghelescu, Costantino Benedetti, Sorin Buga, Charles Cleeland, Oscar A. deLeon-Casasola, June G. Eilers, Betty Ferrell, Mark Green, Nora A. Janjan, Mihir M. Kamdar, Michael H. Levy, Maureen Lynch, Rachel M. McDowell, Natalie Moryl, Suzanne A. Nesbit, Judith A. Paice, Michael W. Rabow, Karen L. Syrjala, Susan G. Urba, Sharon M. Weinstein, Mary Dwyer and Rashmi Kumar

, morphine, morphine-3-glucuronide, morphine-6-glucuronide, and normorphine. 45 This process is largely through the action of the cytochrome P450 enzyme, CYP2D6. It is important to note that CYP2D6 exhibits polymorphism among various ethnic groups and among

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William J. Gradishar, Benjamin O. Anderson, Sarah L. Blair, Harold J. Burstein, Amy Cyr, Anthony D. Elias, William B. Farrar, Andres Forero, Sharon Hermes Giordano, Lori J. Goldstein, Daniel F. Hayes, Clifford A. Hudis, Steven J. Isakoff, Britt-Marie E. Ljung, P. Kelly Marcom, Ingrid A. Mayer, Beryl McCormick, Robert S. Miller, Mark Pegram, Lori J. Pierce, Elizabeth C. Reed, Kilian E. Salerno, Lee S. Schwartzberg, Mary Lou Smith, Hatem Soliman, George Somlo, John H. Ward, Antonio C. Wolff, Richard Zellars, Dorothy A. Shead and Rashmi Kumar

individual patient. Therefore, the panel does not currently recommend assessment of Ki67. The cytochrome P-450 (CYP) enzyme, CYP2D6, is involved in the conversion of tamoxifen to endoxifen. More than 100 allelic variants of CYP2D6 have been reported in

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Therese B. Bevers, Deborah K. Armstrong, Banu Arun, Robert W. Carlson, Kenneth H. Cowan, Mary B. Daly, Irvin Fleming, Judy E. Garber, Mary Gemignani, William J. Gradishar, Helen Krontiras, Swati Kulkarni, Christine Laronga, Loretta Loftus, Deborah J. MacDonald, Martin C. Mahoney, Sofia D. Merajver, Ingrid Meszoely, Lisa Newman, Elizabeth Pritchard, Victoria Seewaldt, Rena V. Sellin, Charles L. Shapiro and John H. Ward

particular isoform of cytochrome P-450 enzyme (CYP2D6) involved in the metabolism of tamoxifen. 81 The consensus of the panel is that alternative medications that have minimal or no impact on plasma levels of endoxifen should be substituted when possible. 81

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Robert A. Swarm, Judith A. Paice, Doralina L. Anghelescu, Madhuri Are, Justine Yang Bruce, Sorin Buga, Marcin Chwistek, Charles Cleeland, David Craig, Ellin Gafford, Heather Greenlee, Eric Hansen, Arif H. Kamal, Mihir M. Kamdar, Susan LeGrand, Sean Mackey, M. Rachel McDowell, Natalie Moryl, Lisle M. Nabell, Suzanne Nesbit, BCPS, Nina O’Connor, Michael W. Rabow, Elizabeth Rickerson, Rebecca Shatsky, Jill Sindt, Susan G. Urba, Jeanie M. Youngwerth, Lydia J. Hammond and Lisa A. Gurski

attention to serotonergic medications (eg, SSRIs) due to risk of serotonin syndrome. Several antidepressants are known inhibitors of hepatic drug metabolism via inhibition of cytochrome P450 enzymes, especially CYP2D6. Tamoxifen is an estrogen receptor