title: Should CYP2D6 inhibitors be administered in conjunction with tamoxifen?
abstract: Tamoxifen has been used for the treatment or prevention of recurrence in patients with estrogen receptor-positive breast cancers. Because CYP2D6 is known to be a key enzyme responsible for the generation of an active tamoxifen metabolite, 'endoxifen', some studies reported that genetic polymorphisms of CYP2D6 that reduced its enzyme activity or coadministration of CYP2D6 inhibitors were associated with the poor clinical outcomes of breast cancer patients treated with tamoxifen. However, there are some discrepant reports for the association between CYP2D6 genotype and clinical outcomes of tamoxifen therapy, probably because of the heterogeneity in sample collection or analysis, including differences in regimen of tamoxifen treatment. A review of published reports regarding the effects of selective serotonin reuptake inhibitors on the pharmacokinetics and/or efficacy of tamoxifen found that concurrent use of strong CYP2D6 inhibitors, especially paroxetine, and possibly others, should be avoided in patients receiving tamoxifen therapy, but there has not been enough evidence for the effects of weak or moderate inhibitors.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Zembutsu
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sasa
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.forename: Taisei
authors.initials: T
authors.lastname: Mushiroda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000235:genetics; D017374:Paroxetine / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019389:Cytochrome P-450 CYP2D6; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D017374:Paroxetine; D011960:Receptors, Estrogen; D017367:Selective Serotonin Reuptake Inhibitors; D013629:Tamoxifen