What is the Winter-Tozer formula?

The Winter-Tozer formula adjusts a measured total phenytoin level for low albumin. Because phenytoin is heavily albumin-bound, hypoalbuminaemia makes the total level underestimate the active free drug. The formula is: corrected = measured divided by ((0.2 times albumin in g/dL divided by 4.4) plus 0.1).

When should I use the renal-failure variant?

Use the renal variant when creatinine clearance is below about 20 mL/min. Uraemia reduces phenytoin binding to albumin, so the adjustment factor drops from 0.2 to 0.1. Using the standard factor in severe renal failure would underestimate the free phenytoin and the risk of toxicity.

Why does low albumin matter for phenytoin?

Only free, unbound phenytoin is pharmacologically active. Roughly 90 percent of phenytoin is normally bound to albumin. When albumin falls, a larger fraction is free even though the measured total looks normal or low, so a patient can be toxic at a total level that appears subtherapeutic.

Is a corrected level as good as a free phenytoin assay?

No. A directly measured free (unbound) phenytoin level is the gold standard and should be used whenever it is available. The Winter-Tozer correction is an estimate for settings where only a total level and albumin are reported.

What albumin value is treated as normal?

This tool uses 4.4 g/dL as the normal reference, matching the original Winter-Tozer publication. Some centres use 4.0 g/dL; the difference shifts the corrected result only slightly. Enter albumin in g/L and the tool converts it to g/dL for you.

What is the Phenytoin Dose Adjustment for Hypoalbuminaemia?

Correct a measured total phenytoin concentration for hypoalbuminaemia using the Winter-Tozer formula, with a renal-failure variant. Enter the measured level, albumin and renal status to estimate the albumin-corrected equivalent. Runs entirely in your browser. It runs free in your browser on Gera Tools, with nothing uploaded.

Phenytoin Dose Adjustment for Hypoalbuminaemia

Name: Phenytoin Dose Adjustment for Hypoalbuminaemia
Creator: Gera Tools
License: https://creativecommons.org/licenses/by/4.0/

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Phenytoin level correction for low albumin

Phenytoin is about 90 percent bound to albumin, and only the free fraction is active. In sick, malnourished or critically ill patients with low albumin, the measured total phenytoin underestimates the active drug — a patient can be clinically toxic while the total level looks reassuringly low. This tool applies the Winter-Tozer formula to estimate the total level that would be seen if albumin were normal, with a separate variant for severe renal failure.

Why this matters clinically

The therapeutic range for phenytoin is typically quoted as 10–20 mg/L (total) or 1–2 mg/L (free). In a patient with an albumin of 20 g/L instead of the normal 40 g/L, a measured total of 8 mg/L can correspond to the same free drug concentration as a total of 14 mg/L in a patient with normal albumin. Interpreting the low number at face value might prompt an unnecessary dose increase — raising the patient’s free phenytoin into toxic territory.

This correction is especially relevant in:

Hospitalised patients with malnutrition, liver disease, or nephrotic syndrome
Elderly patients whose albumin is chronically below 35 g/L
ICU patients on long courses of treatment

How it works

The standard correction is:

corrected = measured / ( (0.2 × albumin_g/dL / 4.4) + 0.1 )

The 0.2 term reflects normal albumin binding and 4.4 g/dL is the reference albumin. In end-stage renal failure (CrCl below ~20 mL/min), uraemic toxins displace phenytoin from albumin, so the binding term drops to 0.1:

corrected = measured / ( (0.1 × albumin_g/dL / 4.4) + 0.1 )

The tool accepts albumin in g/L (the common SI/UK unit) and divides by 10 to get g/dL before applying the formula.

Worked example

Measured phenytoin: 8 mg/L
Serum albumin: 25 g/L (2.5 g/dL) — markedly low
No renal failure

corrected = 8 / ( (0.2 × 2.5 / 4.4) + 0.1 )
          = 8 / (0.1136 + 0.1)
          = 8 / 0.2136
          ≈ 12 mg/L

A level that appeared subtherapeutic (8 mg/L) corrects to 12 mg/L — comfortably within the 10–20 mg/L therapeutic range. Without the correction, a prescriber might unnecessarily increase the dose, risking ataxia or nystagmus from free-phenytoin toxicity.

Limitations and what to do instead

Where a laboratory can report a directly measured free phenytoin level (typically reported as unbound phenytoin, target 1–2 mg/L), use that instead — it needs no formula and has no assumptions to violate. This calculator does not account for concurrent valproate, which also displaces phenytoin from albumin and would push the free fraction higher than either formula predicts. Always interpret results in the context of the patient’s clinical signs and other medication.