Drug induced encephalopathy in six epileptic patients: topiramate? valproate? or both?
Six severe epileptic patients developed stuporous encephalopathy with marked cognitive impairment when topiramate (TPM) and sodium valproate (VPA) were coprescribed for five patients, and when monotherapy with TPM was introduced for one patient. In four patients, ammonaemia increased and then returned to normal after TPM or VPA withdrawal. This severe potential side effect must be recognized. Moreover two distinct mechanisms might explain this toxicity: (1). a pharmacokinetic interaction between VPA and TPM, leading to hyperammonaemia, (2). a pharmacodynamic mechanism due to a direct toxicity of TPM in at-risk epileptic patients.
Latour
Patrick
P
Department of Neurology, Hospital Cavale Blanche, Boulevard Tanguy Prigent, 29200 Brest, France.
Biraben
Arnaud
A
Polard
Elisabeth
E
Bentué-Ferrer
Danièle
D
Beauplet
Anne
A
Tribut
Olivier
O
Allain
Hervé
H
D000293:Adolescent; D000328:Adult; D000641:Ammonia / Q000097:blood; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004569:Electroencephalography; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D000077236:Topiramate; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid; D000641:Ammonia