Additional Information

• Results should always be assessed in conjunction with patient's medical history, clinical examination and other findings.
• Phenytoin is one of the most widely prescribed anticonvulsants and is occasionally used as a myocardial antiarrythmic.
• The total concentration of the drug in the blood consists of the protein-bound fraction and the free fraction, of which only the free drug is considered to be pharmacologically active. Due to the fact that phenytoin is highly bound to plasma proteins (89 - 95%) , any alteration in the protein binding of phenytoin due to uremia, hypoalbuminemia, ingestion of other drugs or age, can result in a significantly different clinical response to a total phenytoin concentration.
• Alcohol, barbiturates, and carbamezapine induce oxidative enzymes, which result in increased metabolism of phenytoin thereby reducing serum concentrations of free phenytoin and reduced pharmacological effect.
• Chloramphenicol, cimetidine, disulfiram, isoniazid and dicumerol compete with phenytoin metabolism thereby resulting in increased serum concentrations of free phenytoin and enhancement of the pharmacological effect.
• Salicylate, valproic acid, phenylbutazone, sulfisoxazole and sulfonylureas compete with phenytoin for serum protein binding sites which results in decreased total phenytoin while free phenytoin remains the same.
• Monitoring serum phenytoin concentrations, along with careful clinical assessment, is the most effective means of improving seizure control, reducing the risk of toxicity and minimizing the need for additional anticonvulsant medication for the following reasons:
  • Serum phenytoin concentrations correlate better with pharmacologic activity than does dosage because of individual differences in absorption, metabolism disease states, concomitant medication, and compliance. Serum concentration monitoring helps physicians individualize dosage regimens.
  • The hepatic enzyme system for metabolizing phenytoin can become saturated within the drug's therapeutic range. When this occurs, small dosage alterations can lead to unexpected drug accumulation and clinical toxicity.
  • Phenytoin is safe and effective only in a narrow range of serum concentrations.