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Dose and administration
- 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.
- 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.
- Neonates and infants with respiratory failure.
- Preterm infants, especially extreme immaturity.
- Neonates with hepatic or renal impairment.
Phenobarbitone induces hepatic metabolism and consequently is associated with a large number of drug interactions. A selected few are given below, and appropriate resources should be consulted before combining other medications with phenobarbitone.
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.|
|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).|
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
- At serum levels >40mcg/ml7: sedation, lethargy, drowsiness, slow feeding, irritability.
- At serum levels >60mcg/ml 7: respiratory depression, apnoea.
- Hypotension; hypothermia; bronchospasm.
- Folate deficiency or hypocalcaemia with prolonged use.
- Hepatitis. Monitor liver function tests during prolonged therapy
- Necrosis after extravasation, due to alkalinity of injection.
- Therapeutic Drug Monitoring 6.
- Blood levels: Time to steady state: 10 - 14 days (possibly longer in neonates)
- Sampling time: immediately before next dose.
- Therapeutic range: 90 - 175 μmol/L (20-40mgL) 10
- Measure serum phenobarbitone levels 12-24 hours after the loading dose, especially if there are breakthrough seizures.
- 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.
- Discontinue phenobarbitone by slowly reducing the maintenance dose.
- 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.
Management of Phenobarbitone administration
Phenobarbitone is a restricted medication, and must be ordered using the red bag and book system, and stored in the locked restricted drug cupboard.
|Solution for Injection||
- Loading doses are charted in mg/dose on stat page of prescription chart.
- Maintenance doses are charted on prescription chart in mg/dose.
Slow IV Infusion
- Dilute to 20 mg in 1 mL:
- Using a 10 ml syringe draw up 9ml Water for Injection.
- In a 2 ml syringe, using a 23 gauge needle, draw up 200 mg (1 ml) phenobarbitone. Measure exactly as there is often overage in the ampoules.
- Add to the Water for Injection to make 20 mg/ml. Mix well.
- Draw up dose from this 20mg/ml phenobarbitone.
- Discard the remaining contents of the 10 ml syringe containing phenobarbitone 20 mg/ml down the sink.
- Filter prior to administration through a Pall 0.2 micron filter.
- Administer by slow IV infusion (do NOT exceed 1 mg/kg/minute) using a syringe pump.
- Compatible with glucose 5%, glucose 10%, and sodium chloride 0.9%. No data available on IVN.
- Do NOT mix with other drugs, IV solutions, blood or blood products.
- Flush line before and after administration of phenobarbitone.
Can be administered with food.
Observation and documentation
- Monitor for barbiturate toxicity signs (laboured breathing, cyanosis, clammy skin, hypotension).
- Nurse on cardiorespiratory monitor.
- Monitor vital signs and document.
- Observe for and document seizure activity.
- Unopened ampoule at room temperature in restricted drug cupboard
- Discard, as above, immediately after use
Follow instructions on bottle label
- Bergman I, Painter MJ, Crumrine PK. Neonatal seizures. Semin Perinatol 1982; 6:54-67.
- Fischer JH, Lockman LA, Zaske D, Kriel R. Phenobarbitone maintenance dose requirements in treating neonatal seizures. Neurology 1981; 31:1042.
- Pawlak RP, Herfert LA. Drug administration in the NICU 2nd Ed 1991. Neonatal Network. p310.
- Gilman JT, Gal P, Duchowny MS et al. Rapid sequential phenobarbital treatment of neonatal seizures. Pediatr 1989; 83: 674-8.
- Reynolds JEF (Ed) Martindale: The Extra Pharmacopoeia. (31st ed). Royal Pharmaceutical Society; 1996: London
- Paediatric Pharmacopoeia, Royal Children's Hospital Melbourne and Leicester Royal Infirmary Children's Hospital, WB Saunders Co. Ltd; 1998: London.
- Young TE, Mangum O.B. (editors) NeoFax (11th ed): A Manual of Drugs Used in Neonatal Care. Acorn Publishing; 1998: Raleigh, North Carolina.
- Stockley I. Drug Interactions 4th ed. The Pharmaceutical Press; 1996: London.
- Evans D, Levene M. Neonatal Seizures. Arch Dis Child Fetal Neonatal Ed. 1998; 78:F70-F75.
- Hey, E, editor. Neonatal formulary. 5th ed. Oxford: Blackwell Publishing; 2007
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- Date last published: 11 November 2011
- Document type: Drug Dosage Guideline
- Services responsible: ADHB Pharmacy, Neonatology
- Editor: Sarah Bellhouse
- Review frequency: 2 years