Acute hepatic injury in four children with Dravet syndrome: valproic acid, topiramate or acetaminophen?
We describe four children with Dravet syndrome treated with the combination of valproic acid (VPA) and topiramate (TPM) who developed transient liver toxicity. The time-interval between fever, administration of acetaminophen, epileptic status and liver enzyme disturbances in our four cases suggests that accumulation of toxic acetaminophen-metabolites is possibly responsible for liver toxicity. If acetaminophen and its metabolites cause those liver problems in children treated with the combination of VPA and TPM, the advice to use acetaminophen for treating fever in children using this combination, should be changed. Only future clinical observations and research can solve this clinical dilemma.
Nicolai
Joost
J
Department of Neurology, University Hospital Maastricht, Maastricht, The Netherlands. jnic@sneu.azm.nl
Gunning
Boudewijn
B
Leroy
Piet L
PL
Ceulemans
Berten
B
Vles
Johan S H
JS
D000082:Acetaminophen / Q000009:adverse effects* / Q000627:therapeutic use; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects* / Q000627:therapeutic use; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology*; D002658:Developmental Disabilities / Q000150:complications*; D004359:Drug Therapy, Combination; D004798:Enzymes / Q000097:blood; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007251:Influenza, Human / Q000150:complications; D008111:Liver Function Tests; D008297:Male; D020190:Myoclonic Epilepsy, Juvenile / Q000150:complications* / Q000188:drug therapy; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D013577:Syndrome; D000077236:Topiramate; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D018712:Analgesics, Non-Narcotic; D000927:Anticonvulsants; D004798:Enzymes; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D000077236:Topiramate; D005632:Fructose; D000082:Acetaminophen; D014635:Valproic Acid