title: Phenytoin intoxication induced by fluvoxamine.
abstract: A patient had phenytoin intoxication after administration of fluvoxamine, a selective serotonin reuptake inhibitor. The serum concentration of phenytoin increased dramatically from 16.6 to 49.1 microg/mL when fluvoxamine was coadministered, although the daily dosage of phenytoin and other drugs had not changed. During phenytoin and fluvoxamine treatment, ataxia, a typical side effect of phenytoin, was observed. The genotypes of CYP2C9 and 2C19, the enzymes responsible for phenytoin metabolism, were homozygous for the wild-type alleles (CYP2C9*1/*1 and 2C19*1/ *1). The interaction may be a result of inhibition of both CYP2C9 and 2C19 by fluvoxamine.
authors.affiliation: Hizen National Hospital, Saga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mamiya
authors.forename: K
authors.initials: K
authors.lastname: Kojima
authors.forename: E
authors.initials: E
authors.lastname: Yukawa
authors.forename: S
authors.initials: S
authors.lastname: Higuchi
authors.forename: I
authors.initials: I
authors.lastname: Ieiri
authors.forename: H
authors.initials: H
authors.lastname: Ninomiya
authors.forename: N
authors.initials: N
authors.lastname: Tashiro
mesh_terms: D000483:Alleles; D000927:Anticonvulsants / Q000097:blood / Q000506:poisoning*; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000506:poisoning*; D001189:Aryl Hydrocarbon Hydroxylases; D001259:Ataxia / Q000139:chemically induced; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004347:Drug Interactions; D005260:Female; D016666:Fluvoxamine / Q000097:blood / Q000506:poisoning*; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D010672:Phenytoin / Q000097:blood / Q000506:poisoning*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000235:genetics
chemical_list: D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D039181:Steroid 16-alpha-Hydroxylase; D016666:Fluvoxamine