# Phenytoin Loading Dose Calculator

## Calculator to quickly achieve therapeutic phenytoin concentrations

### Patient Parameters

 Body weight: kg lbs Height: in cm Gender: Male Female Load method: Fosphenytoin (IV) Phenytoin (IV) Phenytoin (PO)

### Phenytoin Levels

 Assay type: Free Total Current level: mcg/mL Target level: mcg/mL (usual goal 1 to 2 mcg/mL) Albumin: g/dL Dialysis or ESRD: No Yes
Press 'Calculate' to view calculation results.

### About This Calculator

Loading doses of phenytoin (Dilantin) are used to rapidly attain therapeutic drug concentrations. These loading doses may be given on initiation of therapy, or in response to a subtherapeutic drug level in patients at high risk for seizure activity.

#### Calculation Basics

The basis of loading dose calculations involves a drug's volume of distribution (Vd). For phenytoin, a Vd of 0.7 L/kg is used. The following equation is a simple pharmacokinetic equation to estimate a loading dose or resulting serum concentration of a drug.

$$\\ \Delta Cp = \frac{Dose*S}{Vd}$$
ΔCp = (Final concentration - Initial concentration)
Dose = Loading dose of drug (mg)
S = Salt form (0.92 for phenytoin sodium or fosphenytoin)
Vd = Volume of distribution (L/kg)

#### Corrected Total Phenytoin Level

In patients with hypoalbuminemia, a corrected equation must be used to account for reduced phenytoin protein binding. This calculator uses the average of the following correction equations. Note that these equations are a variant of the traditional Winter-Tozer equation, which has been demonstrated to be less accurate (more information).1,2

$$\\ Corrected\;phenytoin\;(equation\;1) = \frac{(Measured\;phenytoin)}{0.25 * Albumin + 0.1} \\ ~ \\ Corrected\;phenytoin\;(equation\;2) = \frac{(Measured\;phenytoin)}{0.29 * Albumin + 0.1}$$

For those with end-stage renal disease, dialysis, or significant uremia, an alternative correction equation is used, which is also a variant of the original ESRD equation but has been demonstrated to be more accurate:3,4

$$\\ Corrected\;phenytoin = \frac{(Measured\;phenytoin)}{0.2 * Albumin + 0.1}$$

#### Adjustment for Obesity

There is limited data regarding an adjustment factor for loading phenytoin in obese patients. The most commonly cited trial5 only included 14 obese patients, of which had a mean weight 78% above ideal body weight. Based on this study alone, the following equation is the suggested obesity adjustment for loading doses:

$$\\ Dosing\;weight = (Ideal\;weight) + 1.33 * (Actual\;weight - Ideal\;weight)$$

#### Fosphenytoin (Cerebyx) and mgPE

Fosphenytoin (Cerebyx) is a more water-soluble prodrug form of phenytoin that allows for faster IV infusion and less risk of extravasation injury. Because its molecular weight is different than that of phenytoin, one milligram of fosphenytoin does not equal one milligram of phenytoin. To avoid confusion, fosphenytoin doses are reported as "mgPE" (milligrams of phenytoin equivalents). Using mgPE, no adjustment is needed when converting between phenytoin and fosphenytoin.

#### Oral vs. IV Loading Doses

Phenytoin oral loading doses may be advantageous in stable patients with subtherapeutic phenytoin concentrations, particularly in those presenting to the emergency department without IV access. Because phenytoin has demonstrated some saturable and erratic oral absorption beyond 400 mg, the use of large oral loading doses is controversial.

Two studies have examined the safety and efficacy of phenytoin oral loading doses.6,7 In both studies, single oral phenytoin doses of 15-20 mg/kg provided therapeutic concentrations (> 10 mg/dL) after about 3 hours, with phenytoin concentrations peaking after about 8 to 12 hours.

Compared to IV, oral loading doses may be advantageous in patients without IV access and who do not require immediate therapeutic levels of phenytoin (eg, status epilepticus). Oral loading may be associated with a slightly higher incidence of nausea and vomiting, and although it achieved therapeutic levels within a few hours, its peak effect is not apparent until 8-12 hours following administration.

### References and Additional Reading

1. Anderson GD, Pak C, Doane KW, et al. Revised Winter-Tozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia. Ann Pharmacother. 1997;31(3):279-84. PMID 9066931.
2. 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):628-36. PMID 23606554.
3. Winter MG, Tozer TN. Chapter 25. Phenytoin. In: Evans WE, Schentag JJ, Jusko WJ. Applied pharmacokinetics: principles of therapeutic drug monitoring. 3rd ed. Vancouver, WA: Applied Therapeutics, 1992:1-44.
4. Soriano VV, Tesoro EP, Kane SP. Characterization of Free Phenytoin Concentrations in End-Stage Renal Disease Using the Winter-Tozer Equation. Ann Pharmacother. 2017 May 1:1060028017707541. doi: 10.1177/1060028017707541. PMID 28470115.
5. Abernethy DR, Greenblatt DJ. Phenytoin disposition in obesity. Determination of loading dose. Arch Neurol. 1985;42(5):468-71. PMID 3994563.
6. Osborn HH, Zisfein J, Sparano R. Single-dose oral phenytoin loading. Ann Emerg Med. 1987;16(4):407-12. PMID 3826809.
7. Ratanakorn D, Kaojarern S, Phuapradit P, Mokkhavesa C. Single oral loading dose of phenytoin: a pharmacokinetics study. J Neurol Sci. 1997;147(1):89-92. PMID 9094065.

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Updated Jul 1, 2017
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