|Reviewed by NICU and Pharmacy|
Phenobarbitone induces hepatic metaolism 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).