PHENOBARBITONE SODIUM

Gardenal sodium

 Reviewed by Dr Malcolm Battin, Brenda Hughes, Beth Loe, Vicki Savage
June 1999
Administration Newborn Drug Protocol Index Newborn Services Home Page

Dose and Administration

  1. Loading: 20 mg/kg by slow IV infusion over 30 minutes, or IM.
    Additional 5-10 mg/kg loading doses may be given if seizures are not controlled.
    Maximum loading dose 40 mg/kg 9.
    Maximum rate of administration 1 mg/kg/min.
  2. Maintenance: 3-5 mg/kg daily IV, IM or PO as a single dose no earlier than 12-24 hours after the loading dose 8.

Indication

  1. Seizures.

Precautions

  1. Neonates and infants with respiratory failure.
  2. Preterm infants, especially extreme immaturity.
  3. Neonates with hepatic or renal impairment.

Drug Interactions

Possible concomitant drug therapy:

Paracetamol Possible decrease in effect of paracetamol due to induction of hepatic enzymes by phenobarbitone. Prolonged use of the combination may lead to liver damage.
Cefotaxime: Increase in skin reaction.
Chlorpromazine: Possible decrease in blood levels of both.
Corticosteroids Increase in clearance of steroid, due to induction of hepatic enzymes.
Folic acid Possible decrease in phenobarbitone level.
Metronidazole Increase in clearance of metronidazole.
Phenytoin: Possible increase in phenobarbitone level. Phenytoin levels may increase or decrease. Monitor levels of both drugs. Watch for phenytoin intoxication if withdrawing phenobarbitone.
Rifampicin Possible increase in clearance of rifampicin
Theophylline Increase in theophylline clearance. Possibly also occurs with caffeine
Propranolol Increase in clearance (propranolol hepatically metabolised). Sotalol: not affected (renally cleared).

Clinical Pharmacology

Phenobarbitone is a central nervous system depressant which is an effective anticonvulsant. It appears to elevate the seizure threshold and limit the spread of seizure activity. Mechanism for pharmacological actions is not known. May involve an increase in inhibitory neurotransmission via enhancement of GABAergic systems.

Absorption virtually complete after PO, IM or rectal administration. Widely distributed with higher distribution volume in neonates (Vd 0.6-1.0 L/kg) and infants than adults. Low binding (10-30%) to human plasma protein. Brain/plasma phenobarbitone ratio approximately 0.7. Ratio decreases with decreasing gestational age. Hepatic metabolism (50-70%) to inactive metabolite. Elimination via the kidney (20-30%) unchanged. Renal clearance enhanced by alkaline urine, diminished by acidic urine. Pharmacokinetics among neonates very variable (elimination half life 40-200 hours).

Possible Adverse Effects

  1. At serum levels >40mcg/ml 7: Sedation, lethargy, drowsiness, slow feeding, irritability.
  2. At serum levels >60mcg/ml 7 : Respiratory depression, apnoea.
  3. Hypotension; hypothermia; bronchospasm.
  4. Folate deficiency or hypocalcaemia with prolonged use.
  5. Hepatitis. Monitor liver function tests during prolonged therapy
  6. Rash.
  7. Necrosis after extravasation, due to alkalinity of injection.

Special Considerations

  1. Therapeutic Drug Monitoring 6
    1. Blood levels: Time to steady state: 10 – 14 days ( possibly longer in neonates)
    2. Sampling time: immediately before next dose.
    3. Therapeutic range: 60 – 120 μmol/L 6
  2. Measure serum phenobarbitone levels 12-24 hours after the loading dose, especially if there are breakthrough seizures.
  3. Measure levels at regular intervals during maintenance therapy especially if other drugs are added to the therapy, or if there is a problem with on-going seizures.
  4. Discontinue phenobarbitone by slowly reducing the maintenance dose.
  5. Management of phenobarbitone overdose and/or toxicity: stop phenobarbitone, supportive therapy (ventilation, volume expansion etc.). Elimination of phenobarbitone may be enhanced by alkalisation of the urine and/or diuretic therapy. Clearance delayed in neonates because of prolonged half life of phenobarbitone.