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Phenytoin – Hypoalbuminaemia Free Level — SCE Neurology MCQ

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HardEpilepsy & Seizure DisordersPhenytoin – Hypoalbuminaemia Free LevelSCE Neurology

A 55-year-old man with epilepsy on phenytoin has a blood test showing phenytoin level of 15 mg/L (therapeutic 10–20 mg/L). His albumin is 20 g/L (low — normal 35–50 g/L). He has hepatic cirrhosis. Is the reported phenytoin level reliable?

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Correct answer: E — No — the total phenytoin level is misleadingly low because phenytoin is highly protein-bound; with low albumin, the free (active) fraction is increased and the patient may be at toxic free phenytoin levels despite a 'therapeutic' total level — a free phenytoin level should be measured

Phenytoin is ~90% protein-bound (to albumin). In hypoalbuminaemia, less phenytoin is bound, increasing the free (pharmacologically active) fraction. A total level of 15 mg/L with albumin of 20 g/L may correspond to a free level equivalent to a total of ~25 mg/L in a patient with normal albumin — potentially toxic. The corrected phenytoin level can be estimated using the Winter-Tozer equation, or ideally a free phenytoin level should be measured directly. This is critical in patients with hepatic failure, renal failure, or any cause of hypoalbuminaemia. A: Total level is misleading with low albumin. C: Increasing the dose would risk toxicity. D: Albumin significantly affects interpretation. E: Albumin, not calcium, affects phenytoin binding.

Reference: BNF – Phenytoin TDM; NICE NG217