Although two small studies found that methylphenidate did notalter phenytoin levels,raised serum phenytoin levels and phenytoin toxicity have been seen in three patients given methylphenidate.
A 5-year-old hyperkinetic epileptic boy taking phenytoin 8.9 mg/kg andprimidone 17.7 mg/kg daily,developed ataxia without nystagmus when he was also given methylphenidate 40mg daily. Serum levels of both antiepileptics were found to be at toxic levels and only began to fall when methylphenidate dosage was reduced (See reference number 1).
A further case of phenytoin toxicity occurred in another child given methylphenidate (See reference number 2). Only one other case has been reported, but this patient was later rechallenged with two drugs and phenytoin toxicity was not seen (See reference number 3).
Furthermore,this interaction has not been seen in clinical studies and observations of 3 healthy subjects(See reference number 3) and more than 11 patients(See reference number 4) taking phenytoin and methylphenidate.
Not fully understood. The suggestion is that methylphenidate acts as an enzyme inhibitor, slowing metabolism of phenytoin by liver and leading to its accumulation in those individuals whose drug metabolising system is virtually saturated by phenytoin.
These appear to be only reports, and any interaction is not established. Concurrent use of phenytoin need not be avoided but be alert for any evi-
dence of toxicity, particularly if phenytoin dosage is high. It would seem prudent to monitor for symptoms of phenytoin toxicity (e.g. blurred vision,nystagmus, ataxia or drowsiness) and take levels if necessary.
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