Genetic Transmission of Cytochrome P450 2D6 (CYP2D6) Ultrarapid Metabolism: Implications for Breastfeeding Women taking Codeine

Parvaz      Madadi; Catherine      Ciszkowski; Andrea      Gaedigk; J.      Steven Leeder; Ronni      Teitelbaum; David      Chitayat; Gideon      Koren

Abstract

The pro-drug codeine is commonly prescribed for postpartum pain relief in North America. The safety of codeine during breastfeeding is related in part to the extent of the active morphine metabolite catalyzed from codeine via the cytochrome P450 2D6 (CYP2D6) enzyme. In mothers who have greater than two functional copies of the CYP2D6 gene (CYP2D6 ultrarapid metabolism phenotype; UM) a substantially higher proportion of morphine is produced. Label changes on codeine-containing medications will highlight the risks associated with this genotype for breastfeeding mothers, but are not supported by translation strategies on how to incorporate this pharmacogenetic knowledge into clinical practice. To address the immediate issue of CYP2D6 UM inheritance in family members of a breastfed infant who succumbed to fatal opioid intoxication and whose codeine-prescribed mother was a CYP2D6 UM, we constructed a pedigree. While the pedigree approach is helpful to aid diagnosis, identify other at risk family members, and simplify pharmacogenetic analysis, its clinical usefulness is dependant on an institutional framework which is not available in most centers at this time.

Keywords: CYP2D6, duplication, codeine, breastmilk, ultrarapid metabolism, pedigree, Genotype, UM, phenotype, Genomic DNA, morphine, toxicity, opioid, NSAIDs, codeine-acetaminophen, pharmacogenetic