When to measure serum concentrations of antiepileptic drugs

For many antiepileptic drugs, the correlation between serum concentration and efficacy or toxicity is poor. Consequently, efficacy of drug treatment is judged by clinical response rather than by target drug serum concentration.

Note: Drug efficacy for epilepsy is measured by clinical response to the antiepileptic drug rather than its serum concentration.

The serum concentration of an antiepileptic drug may be used to:

document concordance with therapy
help diagnose that symptoms or signs are due to toxicity
guide the dosage of phenytoin
adjust the dosage of lamotrigine in pregnancy (see advice).

When the dose is changed, wait at least 5 half-lives of the drug before rechecking the serum concentration, to ensure it has reached the new steady state.

Phenytoin monitoring and dose adjustment are complicated by the drug's nonlinear pharmacokinetics. A small change in the dose can cause a large change in the steady-state serum concentration. If the serum concentration is 30 micromol/L or less (7 mg/L or less), the daily dose of phenytoin in adults can be increased by 100 mg. If the serum concentration is higher than 30 micromol/L, the daily dose should not be increased by more than 50 mg. In patients with hypoalbuminaemia (eg in kidney disease, malnutrition, advanced chronic liver disease), a greater proportion of the phenytoin is free (because of lower protein binding) for the same total concentration.