PHENYTOIN AND VALPROATE

Concurrent use is usually uneventful. Initially total serum phenytoin levels may fall by 20 to 50% but this is offset by a rise in the levels of free (and active) phenytoin, which may very occasionally cause some toxicity. After continued use the total serum phenytoin levels rise once again. Phenytoin also reduces valproate levels. Fospheny- toin, a prodrug of phenytoin, may interact similarly.
Monitor phenytoin and adjust the dose accordingly. When monitoring concurrent use it is important to understand fully the implications of changes in 'total', and 'free' or 'unbound' serum phenytoin levels. Where monitoring of free phenytoin levels is not available, various nomograms have been designed for predicting unbound phenytoin levels during the use of sodium valproate. Consider moni- toring valproate levels for an indication of toxicity if phenytoin is stopped.
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