Phenytoin dose calculations

If the patient has not already received phenytoin then give:

• Intravenous phenytoin sodium 18mg/kg (see Table 1 below). Ensure ECG, blood pressure and respiratory function are monitored throughout the duration of the infusion.

Table 1: Intravenous phenytoin loading dose

Intravenous phenytoin administration

• Give phenytoin over 30 to 40 minutes (rate <50mg/minute). In patients who are elderly, or have pre-existing cardiac disease, give phenytoin over 60 minutes. NB: Adminstration should commence immediately after the mixture has been prepared and completed within 1 hour.
• Ideally, administer undiluted via a syringe pump through a large gauge needle or intravenous catheter into a large forearm vein.
• If dilution is essential, mix with 100 to 250mL sodium chloride 0·9% to a final concentration of <10mg/mL, and administer by infusion pump. Stability of the diluted solution is limited and precipitates may form. Use the solution immediately, ideally with a 0·2 to 0·5micron in-line filter.
• To avoid local venous irritation, inject sterile sodium chloride 0·9% through the vein or catheter before and after each phenytoin infusion.
• Do not administer as a continuous infusion.
• Continuous ECG and blood pressure monitoring is essential during infusion.

If phenytoin is already present but the patient is still not controlled, a 'top-up' loading dose may be useful.

Phenytoin sodium 'top-up' dose (mg) = (20 - measured concentration (mg/L)) x 0·7 x wt (kg)

Table 2 gives the approximate increase in concentration following doses of 250 to 750mg. For example, if the patient weighs 70kg and has a measured concentration of 5mg/L, a single dose of 750mg will increase the concentration to around 20mg/L (5mg/L + 15mg/L).

Table 2: Increase in phenytoin concentration with 'top-up' doses

Phenytoin typical oral doses are 3 to 5mg/kg/day. The first dose should be given 12 to 24 hours after the loading dose.

Oral administration should be used, whenever possible. Administration of phenytoin via enteral feeding tubes is not recommended due to variable absorption of phenytoin. Only use intravenous administration when oral administration is not feasible and where cardiac monitoring is available.

Notes

• There are many drug interactions with phenytoin (consult the BNF Appendix 1 or your clinical pharmacist).
• Phenytoin concentrations increase disproportionately with dose; toxicity may occur if the maintenance dose is increased by more than 25 to 50mg per day. Table 3 below may help with dosage adjustment. Based on the patient's current dose and the measured concentration (columns 1 and 2), column 3 gives a rough guide to interpretation of the result and possible dosage adjustment.
• Different formulations of oral phenytoin preparations may vary in bioavailability. Patients being treated for epilepsy should be maintained on a specific manufacturer’s product.

NB: Table 3 below is for maintenance dose adjustment only. For 'top-up' doses in urgent situations see Table 2 above.

Table 3: Phenytoin maintenance dose adjustment (oral)

Target concentration range: 10 to 20mg/L

Routine monitoring during maintenance therapy

• Trough concentration (ie sample prior to next dose)
• Sample 3 to 5 days after starting a maintenance dose or following a dose change
• Re-analyse 5 to 10 days later as further accumulation may occur.

Monitoring after a loading/top-up dose

• 2 to 4 hours after an intravenous dose or 12 to 24 hours after an oral dose or according to clinical response
• Daily monitoring may be necessary until control is achieved and concentrations stabilise.

Notes

• The interpretation of concentration measurements is altered in:
  • hypoalbuminaemia (especially <32g/L)
  • uraemia
  • pregnancy.

Phenytoin concentrations and low albumin

Phenytoin is highly protein bound but only the unbound concentration is active. In patients with low serum albumin concentrations, a higher proportion of the total (measured) phenytoin concentration is unbound and caution is therefore required when interpreting the result.

The equation below gives an albumin corrected, total phenytoin concentration which can be compared with the target concentration range (10 to 20mg/L).

NB: This equation only gives a rough estimate and the patient's clinical condition should be the most important consideration. Seek advice from neurology or pharmacy if you are unsure what to do.