[Acute phenytoin poisoning secondary to an interaction with ticlopidine].
BACKGROUND
Ticlopidine and phenytoin are two drugs which are widely used in everyday clinical practice, the first as a platelet anti-aggregant and the second as an anti-epileptic agent. Their association is not uncommon, since there is a high incidence of epileptic crises of vascular origin in adults.


METHODS
We present the case of a 77 year old man who had been treated for twenty years with phenytoin for partial crises secondary to a left frontal hematoma. He then followed treatment with ticlopidine for a femoropopliteal bypass, and the dose was later increased because of a vertebro-basilar ictus. On both occasions he presented with ataxia, dysarthria and nausea due to phenytoin intoxication. The blood levels of this drug were above the therapeutic level. The symptoms disappeared and the patient returned to normal after reduction of the dose of phenytoin and suspending treatment with ticlopidine.


CONCLUSIONS
The mechanism of action of ticlopidine at cytochrome P450 level, inhibiting the metabolic clearance of phenytoin, was responsible for this interaction. We have found only three other cases of interaction between these drugs in the literature, and ours is the first to be published in Spain.


CONCLUSIONS
We emphasize the importance of checking plasma phenytoin levels when starting treatment with ticlopidine, since it may be necessary to reduce the dose of phenytoin.
López-Ariztegui
N
N
Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, España.
Ochoà
M
M
Sánchez-Migallón
M J
MJ
Nevado
C
C
Martín
M
M
D000208:Acute Disease; D000368:Aged; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000506:poisoning*; D001189:Aryl Hydrocarbon Hydroxylases; D001259:Ataxia / Q000139:chemically induced*; D002561:Cerebrovascular Disorders / Q000188:drug therapy; D065731:Cytochrome P-450 CYP2C19; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004347:Drug Interactions; D004828:Epilepsies, Partial / Q000188:drug therapy / Q000209:etiology; D006406:Hematoma / Q000150:complications; D006801:Humans; D008658:Inactivation, Metabolic; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors* / Q000502:physiology; D009325:Nausea / Q000139:chemically induced*; D010672:Phenytoin / Q000493:pharmacokinetics / Q000506:poisoning*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D013988:Ticlopidine / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D014715:Vertebrobasilar Insufficiency / Q000188:drug therapy
D000927:Anticonvulsants; D065607:Cytochrome P-450 Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
Intoxicación aguda por fenitoína secundaria a interacción con ticlopidina.