Coprescription of tamoxifen and medications that inhibit CYP2D6.
Evidence 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.
Sideras
Kostandinos
K
Department of Oncology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
Ingle
James N
JN
Ames
Matthew M
MM
Loprinzi
Charles L
CL
Mrazek
David P
DP
Black
John L
JL
Weinshilboum
Richard M
RM
Hawse
John R
JR
Spelsberg
Thomas C
TC
Goetz
Matthew P
MP
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects* / Q000235:genetics; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015412:Mastectomy, Segmental / Q000379:methods; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D018570:Risk Assessment; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D004364:Pharmaceutical Preparations; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen; D019389:Cytochrome P-450 CYP2D6