The effect of CYP2D6 polymorphisms on the response to pain treatment for pediatric sickle cell pain crisis

Objectives To test the hypothesis that children taking hydoxyurea who fail codeine therapy have an increase in reduced-functioning cytochrome P450 2D6 (CYP2D6) alleles. Study design Children with sickle cell disease presenting to air emergency department with a pain crisis unresponsive to codeine were genotyped. The proportion of children with reduced-functioning alleles and CYP2D6 enzyme activity scores <= 1.5, were compared, by x(2) analysis, in children taking hydoxyurea and those with mild disease. Results Of the 73 children completing the study, 42 had reduced-functioning alleles; 82% of the 27 children taking hydoxyurea had reduced-functioning alleles, versus 47% of 36 those with mild disease (P <.05). Activity scores were decreased in 78% of the children taking hydoxyurea and in 44% of those with mild disease (P <.05). The odds ratios of children taking hydoxyurea were 4.9 (95% confidence interval [CI] = 1.5 to 15.9) for having reduced-functioning alleles, and 4.4 (95% CI = 1.4 to 13.4) for having a low activity score. Conclusions Failing codeine therapy for a pain crisis while taking hydoxyurea is associated with an increase in reduced-functioning CYP2D6 alleles. We recommend genetic analysis or trial of a non-CYP2D6 analgesic for these children.