title: Maximum dose - Neonatal Intensive Care Drug Manual
text: Maximum dose
  Total cumulative dose
  Route
  IV, Oral
  Preparation
  IV: Draw up 1 mL (50 mg of phenytoin) and add 9 mL sodium chloride 0.9% to make final volume of 10 mL with a final concentration of 5 mg/mL. Administer through filter immediately after dilution. Do NOT use if solution becomes cloudy or hazy.
  Oral: Shake bottle well prior to measuring dose.
  Administration
  IV: Infuse over 30 minutes (maximum 1 mg/kg/minute) preferably via a central line or large vein (rare risk of purple glove syndrome with peripheral administration). Flush the line with sodium chloride 0.9% before the infusion and after completion of the infusion. IV Maintenance dose can be infused over 5 minutes (maximum 1 mg/kg/minute).
  Oral: May be given with or without feeds but administration with respect to feeds should be consistent. If possible, give apart from other medications.
  Monitoring
  Blood pressure and continuous ECG during stabilisation.
  Infusion-related reactions: hypotension, bradycardia and arrhythmias during infusion.
  Continuous cardiorespiratory monitoring, blood pressure, renal function, liver function, blood glucose, full blood count.
  Long-term therapy: Consider thyroid function tests, calcium, phosphate, 25-hydroxy vitamin D and alkaline phosphatase.
  Therapeutic Drug Concentration Monitoring: Note phenytoin elimination half-life is variable and steady-state may not yet be reached (can take up to 5–10 days) in the initial serum samples.
  Take initial concentration 24 hours after loading dose and then weekly if continued on phenytoin therapy. Concentrations need to be monitored more closely in very preterm or extreme low birth weight infants.
  Adjust the dose as per serum concentration and seizure control.
  In preterm infants, monitoring needs to be individualised because of long and variable half-life.
  Dosage/dose form changes: Serum concentrations should also be checked after dose adjustments or dose form change (e.g. switching from IV to oral) during stabilisation therapy with similar timing as above.
  Target Range: Note reference ranges are in total phenytoin concentration; reference ranges are different for free phenytoin concentrations. Serum therapeutic range infants ≤ 28 days: 6–15 mg/L (24–60 micromol/L); infants > 28 days: 10--20 mg/L (40–80 micromol/L).
  In severely ill infants and those with hypoalbuminaemia, uremia or concomitant valproic acid, consider measuring free phenytoin concentrations. For free phenytoin, target range is 0.5 to 1.4 mg/L (2 to 5.6 micromol/L). Typical free phenytoin is one-tenth of total phenytoin as phenytoin is 90% protein bound.
  If total concentration is above upper range but below 30 mg/L (120 micromol/L), withhold dose. Concentrations above 30 mg/L (120 micromol/L) are considered toxic and infant may display signs of overdose and should be monitored especially for cardiovascular symptoms/signs.
  Adjustment of dose according to serum concentration: Phenytoin does not follow linear kinetics so an increase in dose may cause a disproportionate increase in serum concentration. If a dose increase is required, do so gradually (no more than 10% of the daily dose at any one time) and consult pharmacy/neurologist.
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