Phenytoin Correction Calculator (Sheiner-Tozer)
Phenytoin is 90% protein-bound, so a "therapeutic" total level in a hypoalbuminemic patient can hide free-drug toxicity. Correct the level, know when the equation itself fails, and know when to just order the free level.
Reviewed by Zaka Ahmed, MD Clinical reference · 3 min read
Phenytoin Correction
Enter the measured total phenytoin and serum albumin, and mark whether the patient has significant renal failure (CrCl below ~20 mL/min or dialysis) — binding changes there use a different coefficient.
The albumin-corrected level and its interpretation appear here.
Educational tool only. The Sheiner-Tozer correction is an estimate with known inaccuracy in critical illness, pregnancy, drug interactions (notably valproate co-administration), and extremes of albumin — a measured free phenytoin level is definitive when the decision matters. This does not replace clinical judgment.
Clinical notes & interpretation Scoring guidance, pitfalls, FAQs, and references
Why the total level misleads
Phenytoin is roughly 90% albumin-bound, and only free drug crosses into brain. Hypoalbuminemia — near-universal in prolonged hospitalization, malnutrition, and critical illness — raises the free fraction while the lab reports a reassuring total. The Sheiner-Tozer equation rescales the total to what it would be at normal albumin: measured ÷ (0.2 × albumin + 0.1), with the coefficient dropping to 0.1 in severe renal failure, where uremia additionally displaces drug from albumin. The corrected number is then read against the familiar 10–20 µg/mL range.
Where this bites on a neuro service
Post-stroke seizures and status epilepticus still put patients on fosphenytoin, and the patients most likely to need levels — elderly, malnourished, critically ill, renal failure — are exactly those in whom totals mislead. The classic trap: an ICU patient with albumin 2.0 and a total level of 12 who is "therapeutic" on paper and toxic in fact (corrected ≈24), with confusion or worsening exam attributed to the underlying brain injury. The reverse trap exists too: chasing a "subtherapeutic" total with escalating doses in a hypoalbuminemic patient who is already free-level therapeutic. When the stakes are real — refractory seizures, unexplained decline, drug interactions such as valproate (which both displaces phenytoin and inhibits its metabolism) — skip the arithmetic and order the free level; the equation is a bridge, not an oracle.
Frequently asked questions.
What is the target range?
Total-equivalent 10–20 µg/mL, corresponding to a free level of roughly 1–2 µg/mL. Clinical response and toxicity always outrank the number.
When is the correction unreliable?
Severe hypoalbuminemia (<2.5 g/dL), critical illness, pregnancy, dialysis, and valproate co-administration. In those settings, measure free phenytoin directly.
Why do small dose changes cause big level swings?
Phenytoin saturates its metabolizing enzymes within the therapeutic range (Michaelis-Menten/zero-order kinetics), so clearance stops scaling with concentration. Titrate in small increments and recheck.
References.
- Winter ME. Basic Clinical Pharmacokinetics. 5th ed. Lippincott Williams & Wilkins; 2010 — phenytoin chapter (Sheiner-Tozer correction).
- Kane SP, Bress AP, Tesoro EP. Characterization of unbound phenytoin concentrations in neurointensive care unit patients using a revised Winter-Tozer equation. Ann Pharmacother. 2013;47(5):628–636. PubMed
- von Winckelmann SL, Spriet I, Willems L. Therapeutic drug monitoring of phenytoin in critically ill patients. Pharmacotherapy. 2008;28(11):1391–1400. PubMed