Phenytoin
Phenytoin is an antiepileptic drug used in the treatment of complex partial seizures, generalised tonic-clonic seizures, prevention of seizures following head trauma and status epilepticus. It is also used in ventricular arrythmias.
- To guide dose-adjustment towards optimal drug exposure to optimise drug efficacy while minimising toxicity
- To aid diagnosis
- Differentiating disease resistant to drug versus inadequate drug exposure
- Differentiating adverse drug reaction versus underlying disease
Assay details
See Phenytoin – Canterbury Health Laboratories (chl.co.nz)
Timing of concentration sample collection
- With respect to dose interval:
- Oral dosing: measure at the trough concentration, just prior to the next oral dose.
- IV loading dose: if it is critical to know the concentration to check whether a therapeutic concentration was reached, serum concentration may be measured within 2-4 hours. If not critical, check in 5 days.
- Phenytoin concentration should be measured immediately if toxicity is suspected
- With respect to treatment course:
- Concentrations should be measured at least 5 days after initiating therapy or after a change in dose when the new steady state concentration will be achieved. Please contact Clinical pharmacology via Medicines Information for advice on sample timings. This is especially important at high or supra-therapeutic concentrations due to saturable kinetics and therefore variable clearance (the time to steady state can increase to weeks).
Alternatives to monitoring concentration
- Clinicians are encouraged to consider alternative and/or additional gauges of drug effect dependent on clinical presentation, turnaround time of the assay and clinical signs of efficacy or toxicity.
- If toxicity is suspected monitor respiratory rate, heart rate, blood pressure, ECG and GCS.
Reference Range
The trough concentration reference range for total phenytoin is 40 – 80 micromol/L for the Canterbury Health Lab assay.
The trough concentration reference range for unbound (free phenytoin) is 4 – 9 micromol/L for the Canterbury Health Lab assay.
Factors that may give a false assay result
- Hypoalbuminaemia: when the albumin concentration is less than 30 g/L, the free phenytoin concentration should be measured directly.
- Pregnancy may cause a low albumin.
- Free phenytoin should be measured routinely in ICU patients as many have low albumin concentration.
Dose individualisation and adjustment
- Non-linear saturable metabolism; small changes in dose may produce disproportionally large changes in plasma concentration.
- Small dose adjustments (10 – 30 mg) should be made at the upper end of the therapeutic range
Other dosing considerations
- Phenytoin is metabolised by CYP2C19 and CYP2C9. Significant drug interactions exist which may require dose adjustments.
- Consider using a reduced maintenance dose initially in elderly patients or those with impaired renal or hepatic function.
- Defined oral dose forms can lead to issues with practical prescribing. Where possible use whole tablet dosing (rounding to the nearest whole tablet).
- Loading dose: 15 – 20 mg/kg (IV or Oral)
- Common maintenance dose: 5 – 6 mg/kg (IV or Oral) daily (range 2 – 7 mg/kg).
Medicines Information: phone 03 364 0900 or email medicines.information@cdhb.health.nz
Hung C, Lin C, Chen C, et al. Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Ther Drug Monit. 2004;26:534-40.
Patsalos, P.N., Berry, D.J., Bourgeois et al., Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. 2008;49(7):1239-76
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Schachter SC. Antiseizure medications: Mechanism of action, pharmacology, and adverse effects. In: UpToDate, Garcia P, Dashe JF (Ed), UpToDate, Waltham, MA. (Accessed February 12, 2024.)
Schmidt D, Haenel F. Therapeutic plasma levels of phenytoin, phenobarbital, and carbamazepine: individual variation in relation to seizure frequency and type. Neurology. 1984;34:1252–1255.
Last updated
December 2024