Pathology Handbook

Phenytoin

Synonyms

Epanutin

Clinical Indications

Phenytoin is a primary anticonvulsant for prophylaxis and treatment of partial and generalised tonic-clonic seizures. It is particularly appropriate where once daily dosing is an advantage. It does however have unpleasant comestic effects on long term treatment. The main indications for monitoring are:

  • On initiating therapy
  • During I.V. therapy in status epilepticus
  • Unexpected deterioration in seizure control
  • As an adjunct to the diagnosis of toxicity
  • When interacting drugs are added or withdrawn
  • In pregnancy

Drug Kinetics

Phenytoin is metabolised by the hepatic mixed-function oxidase system, which has a limited capacity and can become saturated at phenytoin concentrations within the target range. When levels are close to the saturation point a small increase in dose can result in a marked increase in serum concentration: this saturation point varies widely between patients.

Request Form 

Request on ICE
Please state dosage and time of last dose on request form.

Availability

Available at all times. Please contact the laboratory regarding urgent requests.

Specific Criteria

A trough sample is required - i.e. pre-dose

Patient Preparation

Steady state levels. This is 4-5 days following a change in dose.

Turnaround Time

Same Day

Specimen

Serum in yellow top (SST) tube

Volume

2 ml

Container

Vacutainer gold top

Lab Handling

Samples should be analysed same day if left on gel.

Causes for Rejection

Unlabelled sample

Target Range

5 - 20 mg/L

NOTE THAT LEVELS ARE REPORTED IN mg/L; to convert mg/L to ┬Ámol/L multiply by 3.96

This range is indicative only, and some patients tolerate higher levels and require them to achieve effective control. Other patients are adequately controlled at lower concentrations and there is no need to use higher doses in such patients.
Phenytoin is over 90% protein-bound in healthy adults on monotherapy, but binding is substantially reduced in neonates, pregnancy, renal or hepatic disease. In such cases, effective or toxic free drug levels are obtained at lower total serum phenytoin levels.

Toxicity

Symptoms of neurotoxicity (nausea, vomiting, tremor. ataxia) are increasingly frequent as levels exceed 20 mg/L

Overdose

Following overdose and confirmation of toxicity there is not a case for continuous monitoring of levels to decide when to resume therapy. Phenytoin half-life is usually between 24 and 48 hours but due to the saturation kinetics displayed, levels will gradually fall and then plummet i.e. half-life will be dependant on serum levels. Usually, phenytoin is stopped for 2 to 3 days and then the normal dose resumed. Serum levels should be monitored 7-10 days later after steady state has been obtained.