Corrected Phenytoin Calculator (Sheiner-Tozer)
Correct a total phenytoin level for low albumin with the Sheiner-Tozer (Winter-Tozer) equation, the Anderson revision or the kidney-failure version, and compare it with the 10–20 mg/L range.
How it works
Corrected phenytoin = measured ÷ (0.2 × albumin g/dL + 0.1) (Sheiner-Tozer) · Anderson revision: ÷ (0.275 × albumin + 0.1) · CrCl < 10 mL/min: ÷ (0.1 × albumin + 0.1) · 1 mg/L = 3.964 µmol/L; albumin g/L ÷ 10 = g/dL
Phenytoin is about 90% bound to albumin and only the free fraction is active. When albumin is low (illness, malnutrition, pregnancy, liver disease, the elderly) or binding is displaced by uremia, the free fraction rises, so a “low” total level can actually reflect a therapeutic or even toxic free level. The Sheiner-Tozer equation estimates what the total level would be at a normal albumin; Anderson et al. (1997) found a factor of 0.275 more accurate in trauma and elderly patients, and a 0.1 factor is used in kidney failure. These equations tend to underestimate free levels in critically ill patients, so measure a free phenytoin level (normal 1–2 mg/L) whenever possible.
Worked example
A total phenytoin level of 8 mg/L with albumin 25 g/L (2.5 g/dL) and normal kidney function: corrected = 8 ÷ (0.2 × 2.5 + 0.1) = 8 ÷ 0.6 = 13.3 mg/L (53 µmol/L) — within the 10–20 mg/L range, so the dose probably does not need increasing despite the “low” measured level.
Sources: Sheiner LB, Tozer TN. Clinical pharmacokinetics: the use of plasma concentrations of drugs. In: Clinical Pharmacology: Basic Principles in Therapeutics, 1978 · Anderson GD et al. Revised Winter-Tozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia. Ann Pharmacother 1997;31:279–84
Frequently asked questions
Why correct phenytoin for albumin?
Because the lab measures total phenytoin (bound + free), while only the free drug acts. With low albumin a larger share is free, so the total underestimates the effect. Raising the dose to “fix” a low total level can cause toxicity.
What is the therapeutic range of phenytoin?
Total phenytoin 10–20 mg/L (µg/mL), or 40–79 µmol/L; free phenytoin 1–2 mg/L. Nystagmus typically appears above 20 mg/L, ataxia above 30 and lethargy above 40.
Which correction equation is most accurate?
All albumin-based equations are approximations. Studies suggest 0.275 (Anderson) or 0.29 perform better than the classic 0.2 in many groups, but none is reliable in critical illness — a measured free level is preferred.
Does the correction apply to fosphenytoin?
Yes. Fosphenytoin is converted to phenytoin, and levels are reported as phenytoin; wait at least 2 hours after an IV dose (4 hours after IM) before measuring.
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Educational calculation for health professionals only, not medical advice or a prescription. Check every dose against the current product label, local protocols and a pharmacist, and adjust it for the individual patient.