DRESS after IV phenytoin associated with cytochrome P450 CYP2C9*3 homozygosity

Phenytoin is a first-generation antiepileptic drug, which is used in the treatment of focal seizures and as standard of care for patients with benzodiazepine-refractory status epilepticus. Elimination of phenytoin occurs primarily via CYP enzyme–dependent hepatic clearance. The first step is the para-hydroxylation from active phenytoin to inactive hydroxy-phenytoin, which is dependent on CYP2C9 and, to a lesser extent, on CYP2C19. A considerable disparity in CYP2C9 alleles exists, and the frequency varies among different ancestry groups, the CYP2C9*3 allele being less frequent in Caucasians and more frequent in Asian populations.1,2 Homozygosity for the CYP2C9*3 allele leads to a significant reduction in enzyme activity, resulting in increased plasma levels of phenytoin.3