Guideline for Phenytoin Dose Calculations

1. Initial loading dose of phenytoin for status epilepticus

If the patient has not already received phenytoin then give:

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

Table 1 - IV phenytoin loading dose

Phenytoin IV administration

• Give phenytoin over 30-40 minutes (rate <50mg/minute). In patients who are elderly, or have pre-existing cardiac disease, give phenytoin over 60 minutes. N.B. Administration of the diluted solution 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 IV catheter into a large forearm vein.
• If dilution is essential, dilute doses <1g in 100ml of sodium chloride 0.9% and doses >1g in 250ml of sodium chloride 0.9%. Give through an in-line filter (0.22 - 0.5microns) via an infusion pump.
• 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, blood pressure and respiratory rate monitoring is required during infusion as there is a risk of hypotension and bradycardia.

2. 'Top-up' loading dose of phenytoin for status epilepticus

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 weight (kg)

Table 2 gives the approximate increase in concentration following doses of 250–750mg. 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

3. Maintenance dose of phenytoin

Typical phenytoin doses are 3–5mg/kg/day. The first dose should be given 12–24 hours after the loading dose.

Oral or nasogastric administration should be used, whenever possible. Only use intravenous administration when these options are not feasible and where cardiac monitoring is available.

Notes

• Phenytoin sodium 100mg capsules / tablets / injection = phenytoin 15ml (90mg) suspension (6mg/ml).
• There are many drug interactions with phenytoin (consult the BNF or your clinical pharmacist).
• Phenytoin concentrations increase disproportionately with dose; toxicity may occur if the maintenance dose is increased by more than 25–50mg 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.

N.B. 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

4. Therapeutic Drug Monitoring of Phenytoin

Target concentration range: 10–20mg/L

N.B. A plasma level of 5–10mg/L may be adequate for some patients.

Routine monitoring during maintenance therapy

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

Monitoring after a loading / top-up dose

• 2–4 hours after an IV dose or 12–24 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 (10–20mg/L).

*Midpoint of reference range for serum albumin

N.B. 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.