Tamoxifen Information of Interaction Related CYP Inhibitors

Abstract

Objective: Tamoxifen is a drug that is frequently administered for 5 years to treat hormone receptor-positive breast cancer in premenopausal women.  Metabolism of tamoxifen by cytochrome P450 enzymes such as CYP3A4 and CYP2D6 is required for drug efficacy.  However, reports suggest that the effect of tamoxifen is attenuated in the presence of CYP2D6 inhibitors.  In this study, I evaluated drug-drug interactions that may attenuate tamoxifen action for improved pharmaceutical management.
Data Source: Potential interactions were evaluated by using the tamoxifen package insert, Kyoto Encyclopedia of Genes and Genomes (KEGG), Pharmaceuticals and Medical Devices Agency (PubMed), and Lexicomp Online.  We have searched the paper using the PubMed and JDream III.
The Choice of Research: The paper about the interaction related CYP2D6 and 3A4 of tamoxifen.
Results and Conclusion: The use of tamoxifen is often long term; however, adverse effects such as hot flashes, can cause poor regimen adherence.  Although selective serotonin reuptake inhibitors (SSRIs) can effectively treat menopausal hot flashes, many SSRIs inhibit CYP2D6.  In particular, paroxetine has been reported to adversely affect tamoxifen metabolism.  There are 31 drugs and 843 compounds that inhibit CYP2D6.  Thus, it is necessary to avoid these combinations.  In addition, there are many CYP2D6 gene polymorphisms that have been identified in Japanese patients, and some reports indicate that they affect tamoxifen efficacy.  Therefore, in order to continue use of these medications without attenuating the effect of tamoxifen, development of medical database which can be updated daily is required to avoid CYP-related interactions.