GGC Medicines


Adult Therapeutics Handbook

Guideline for Phenytoin Dose Calculations

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

Weight (kg) IV Loading Dose (mg) Volume of IV phenytoin (ml) (vial = 250mg/5ml)
35-44 700 14
45-54 900 18
55-64 1100 22
65-74 1250 25
75-84 1450 29
85-94 1600 32
>94 1800 36

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. 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 IV catheter into a large forearm vein.
  • If dilution is essential, mix with 100–250ml sodium chloride 0.9% to a final concentration of <10mg/ml, and administer by infusion pump.
  • Use the solution immediately, ideally with a 0.2–0.5micron 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.

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 wt (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

  Concentration increase with 'top-up' dose
Dose / Weight 50 kg 60 kg 70 kg 80 kg
250 mg 7 mg/L 6 mg/L 5 mg/L 4.5 mg/L
500 mg 14 mg/L 12 mg/L 10 mg/L 9 mg/L
750 mg 21 mg/L 18 mg/L 15 mg/L 13.5 mg/L

3. Maintenance dose of phenytoin

Phenytoin typical 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 = 15ml (90mg) suspension (6mg/ml).
  • 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 25–50mg 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

Measured concentration Current dose Maximum dose increase
< 5mg/L <4.5mg/kg/day 100mg
4.5–6mg/kg/day Check compliance
5–10mg/L 4.5–6 mg/kg/day 50mg
>6mg/kg/day Check compliance
10–20mg/L - 25mg

4. Therapeutic Drug Monitoring of Phenytoin

Target concentration range: 5–20mg/L

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).

Corrected phenytoin concentration = Measured phenytoin concentration
(0.9 x Albumin (g/L) / 42*) + 0.1

*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.

Decision making algorithm for the administration of phenytoin formulations