Reviewed by Dr Malcolm Battin, Brenda Hughes, Julia Blagburn, Robyn Wilkinson
July 1999
Administration Newborn Drug Protocol Index Newborn Services Home Page

Dose and Administration

  1. Loading dose: 20 mg/kg by slow IV infusion over 60 minutes 5.
  2. Maintenance dose: 2-4 mg/kg/dose twice a day by slow IV infusion, or PO 6.
    Administer at a rate not faster than 1.0 mg/kg/minute 6.
    The maintenance dose needs to be monitored and adjusted according to blood levels.


  1. Seizures refractory to phenobarbitone therapy alone.


  1. Sinus rhythm bradycardia, sinoatrial or atrioventricular block.


  1. Known hypersensitivity to phenytoin.
  2. Neonates with jaundice, respiratory failure, hypotension or heart failure.
  3. Preterm infants, especially extreme immaturity.
  4. Neonates and infants with hepatic or renal impairment.

Drug Interactions7

Phenytoin may increase the levels of: Phenobarbitone.
Phenytoin may decrease the levels or activity of: Paracetamol, caffeine, corticosteroids, diazoxide, digoxin, dopamine, fentanyl, furosemide, theophylline.
Phenytoin levels may be decreased by: Phenobarbitone, rifampicin, theophylline.
Phenytoin levels may be increased by: Fluconazole, ranitidine.
Phenytoin levels may be altered by: Chlorpromazine, benzodiazepines.
Phenytoin levels may be altered by: Interfere with thyroid function tests, and produce lower than normal values for metyrapone suppression tests.

Clinical Pharmacology

Phenytoin is an anticonvulsant with a primary site of action in the motor cortex. Environmental changes or excessive stimulation can cause a reduction in membrane sodium gradient. Phenytoin causes an efflux of sodium from neurons and therefore stabilises the threshold against over-activity in those brain stem centres responsible for the tonic phase of grand mal seizures 9. Absorption from gastrointestinal tract and intramuscular injection sites erratic. Phenytoin has high binding (85-90%) to plasma protein. Bilirubin displaces phenytoin from albumin binding sites resulting in higher percentage of unbound drug in plasma. Elimination via the kidney. Pharmacokinetics are dose-dependent over the therapeutic range and unpredictable in the neonate. Relatively small margin between full therapeutic effect and a minimally toxic dose of phenytoin.

Possible Adverse Effects

  1. Injection is very alkaline –therefore may result in venous irritation and phlebitis. Avoid extravasation.
  2. Observe diluted solution, for crystal formation.
  3. Rapid administration may result in hypotension, CNS depression, cardiac arrhythmias, and impaired cardiac conduction.
  4. Gastrointestinal disturbances (nausea, vomiting, constipation).
  5. Overdosage may result in hypotension, coma, respiratory depression. Nystagmus may be an indication of toxicity.
  6. Possible interference of Vitamin D and folate metabolism. Megaloblastic anaemia.
  7. Hypersensitivity reactions eg. skin rashes. Bullous or purpuric rashes are indicators to withdraw therapy as they may be symptoms of rare but severe reactions eg. toxic epidermal necrolysis.
  8. Hyperglycaemia.

Special Considerations

  1. DO NOT administer phenytoin intramuscularly. Crystallisation in muscle results in erratic absorption and severe pain.
  2. If used for maintenance therapy:
    1. Monitor: Liver function and full blood count.
    2. Therapeutic Drug Monitoring (TDM) 6: Time to steady state: 1 to 2 weeks (variable).
      Serum level (neonate): 40-80 μmol/L 8.  
      Measure serum phenytoin levels at least 12 - 24 hours after IV loading dose and at regular intervals during maintenance therapy.
  3. Management of phenytoin overdose and/or toxicity: stop phenytoin, supportive therapy (ventilation, volume expansion, inotropes, and/or anti-arrhythmic agents).