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.

Keywords::

• chemoprevention
• CYP2D6
• CYP2D6 inhibitor
• endoxifen
• genotype
• prophylactic mastectomy
• tamoxifen

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Notes

Data taken from [24,103].