Phenytoin intoxication induced by fluvoxamine.
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.
Mamiya
K
K
Hizen National Hospital, Saga, Japan.
Kojima
K
K
Yukawa
E
E
Higuchi
S
S
Ieiri
I
I
Ninomiya
H
H
Tashiro
N
N
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
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