Format

Send to

Choose Destination
Pharmacogenet Genomics. 2014 Jul;24(7):367-9. doi: 10.1097/FPC.0000000000000051.

Profound reduction in the tamoxifen active metabolite endoxifen in a patient on phenytoin for epilepsy compared with a CYP2D6 genotype matched cohort.

Author information

1
Department of Medicine, Division of Clinical Pharmacology, Western University, London, Ontario, Canada.

Abstract

Tamoxifen is a prodrug, requiring cytochrome P450 enzyme-mediated metabolism to form the active metabolite endoxifen. We identified a case of drug-drug interaction involving tamoxifen and phenytoin, associated with a markedly lower endoxifen level than predicted. The patient is a 49-year-old woman, genotyped as a cytochrome P450 2D6 (CYP2D6) extensive metabolizer, chronically taking phenytoin for a seizure disorder. The plasma endoxifen level 2 months after starting tamoxifen was 4.72 nmol/l, the lowest level we have seen in our clinic among patients with CYP2D6 extensive metabolizer genotypes (n=195). To our knowledge, this is the first report documenting the extent of induction in terms of both tamoxifen and endoxifen levels during concomitant phenytoin therapy, and this effect would likely result in loss of therapeutic benefit from tamoxifen. Phenytoin should therefore not be used concurrently with tamoxifen for extended periods of time unless a therapeutic drug (endoxifen) monitoring strategy is utilized.

PMID:
24915025
DOI:
10.1097/FPC.0000000000000051
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center