# Phenytoin (Dilantin) Correction Calculator

## Patient Parameters

 Albumin g/dL Total phenytoin mcg/mL

## Correction Factors

Press 'Calculate' to see the proposed recommendations.

Due to its narrow therapeutic index and non-linear pharmacokinetic profile, phenytoin therapeutic drug monitoring is recommended. Because phenytoin is highly protein bound and only unbound drug is capable of crossing the blood-brain barrier to exert its pharmacologic effect, unbound (free) phenytoin levels may be more clinically relevant than total levels to maximize efficacy and minimize toxicity.1,2

Although unbound (free) phenytoin levels can be measured by a laboratory assay, this method may not be available on-site at all institutions, or the turnaround time for a result may be so long that it limits its clinical utility. The Winter-Tozer equation was developed to help clinicians estimate an unbound (free) phenytoin concentration based on a total phenytoin level and a serum albumin level.

### Winter-Tozer Equation

The original Winter-Tozer equation3 (displayed below) was initially developed in patients with epilepsy assuming a normal serum albumin of 4.4 g/dL and a free fraction of 10%. By simplifying the equation, a coefficient of '0.2' has demonstrated good correlation to free phenytoin concentrations in most patients without significant comorbidities.4 In patients with renal dysfunction or end-stage renal disease, a coefficient of '0.1' may be more appropriate due to reduced protein binding secondary to uremia.3

\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{\frac{Albumin}{4.4}*0.9+0.1} \\ \\ \\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{0.2 * Albumin + 0.1} \\ \\ Renal\;dysfunction: \\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{0.1 * Albumin + 0.1}

### Correction Factors

There is considerable controversy regarding the accuracy of the Winter-Tozer equation in a variety of patient populations. In a study of patients with hypoalbuminemia and normal renal function (CrCl > 50 mL/min and albumin < 4.0 g/dL), the Winter-Tozer equation (using a coefficient of 0.2) significantly underpredicted true free phenytoin concentrations.5 In the same study,5 the Winter-Tozer equation (using a coefficient of 0.1) was poorly correlated to true free concentrations in patients with renal failure on dialysis.

In critically ill patients, the Winter-Tozer equation may be problematic due to a high incidence of renal dysfunction, large changes in fluid status, and hypoalbuminemia. While one study of neurosurgical patients showed a strong correlation,6 other literature suggests that a coefficient of '0.25' may be more appropriate, particularly in elderly patients or patients with severe head trauma.7

### Correction Factors for this Calculator

On the basis of available literature, the following coefficients are used by this clinical calculator:

• No comorbidities: 0.2 1-3
• ESRD: 0.1 1
• Severe head trauma: 0.25 7
• Age > 65 years: 0.25 7