Abstract
Therapeutic drug monitoring of phenytoin is carried out to ensure effective and safe levels. Some of the factors
complicating phenytoin dosing include a narrow therapeutic window, high degree of protein binding, and nonlinear pharmacokinetics. However, serum drug levels should only be taken when there is a clear indication to
guide patient management. Scenarios where monitoring levels may be clinically useful include: (1) establishing an
individual therapeutic concentration, (2) aiding in diagnosis of clinical toxicity, (3) assessing patient compliance,
and (4) guiding dosage adjustments in patients likely to have greater pharmacokinetic variability. This paper
aims to provide an overview on of the correct timing and interpretation of phenytoin levels. It will also address
phenytoin dosing, other monitoring parameters, and management of phenytoin adverse effects.
Keywords: Pharmacokinetics, Phenytoin, Therapeutic drug monitoring
WHAT IS PHENYTOIN?
Phenytoin is an anticonvulsant licensed for the
management of generalised tonic-clonic (grandmal) seizures and complex partial (psychomotor,
temporal lobe) seizures1. It is also approved by
the United States Federal Drug Authority for the
prevention and treatment of seizures occurring
during or after neurosurgery2.
WHY IS THERAPEUTIC DRUG MONITORING OF
PHENYTOIN NECESSARY?
Phenytoin has a narrow therapeutic window hence
a fine balance must be found between efficacy and
dose-related side effects3. Since phenytoin is highly
protein-bound and free (unbound) phenytoin is the
component producing the pharmacological effect,
any factor which changes the protein binding of
phenytoin would be expected to alter the free
drug levels. As such, interactions with other drugs
(drug-drug interactions) or with diseases e.g. renal
impairment, uraemia, and critical illness (drugdisease interactions) may give rise to changes
in phenytoin pharmacokinetics and/or efficacy
and toxicity.
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Phenytoin TDM
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Review
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