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Coprescription of tamoxifen and medications that inhibit CYP2D6 Sideras K; Ingle JN; Ames MM; Loprinzi CL; Mrazek DP; Black JL; Weinshilboum RM; Hawse JR; Spelsberg TC; Goetz MPJ Clin Oncol 2010[Jun]; 28 (16): 2768-76Evidence has emerged that the clinical benefit of tamoxifen is related to the functional status of the hepatic metabolizing enzyme cytochrome P450 2D6 (CYP2D6). CYP2D6 is the key enzyme responsible for the generation of the potent tamoxifen metabolite, endoxifen. Multiple studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-treated women; the majority of studies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations and a greater risk of breast cancer recurrence. As a result, practitioners must be aware that some of the most commonly prescribed medications coadministered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentrations and potentially increasing the risk of breast cancer recurrence. After reviewing the published data regarding tamoxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-treated patients, we are providing a guide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen.|*Drug-Related Side Effects and Adverse Reactions[MESH]|Antineoplastic Agents, Hormonal/administration & dosage/metabolism[MESH]|Breast Neoplasms/*drug therapy/*genetics/mortality/surgery[MESH]|Chemotherapy, Adjuvant[MESH]|Cohort Studies[MESH]|Cytochrome P-450 CYP2D6/*drug effects/genetics[MESH]|Drug Interactions[MESH]|Drug Therapy, Combination[MESH]|Female[MESH]|Follow-Up Studies[MESH]|Humans[MESH]|Mastectomy, Segmental/methods[MESH]|Pharmaceutical Preparations/administration & dosage[MESH]|Practice Guidelines as Topic[MESH]|Retrospective Studies[MESH]|Risk Assessment[MESH]|Tamoxifen/administration & dosage/*analogs & derivatives/analysis/*metabolism[MESH]|Treatment Outcome[MESH] |
