Phenobarbitone

Side-effects

Possible side effects:

• CNS depression and sedation are the most common side effects, particularly when the drug is initiated, and it can improve with continued administration.
• Some patients can have anxiety, irritability, or aggression, sometimes seen after a loading dose in the acute setting.

Less common side effects:

• Respiratory depression, especially with intravenous administration – care should be taken in patients with multiple other neurological co-morbidities.
• Hypotension with intravenous administration.
• Ataxia.
• Rash.
• Stevens-Johnsons Syndrome (SJS)/Toxic epidermal necrolysis spectrum is rare but has been described. There is cross-reactivity with respect to risk for SJS across other aromatic agents - carbamazepine, phenytoin and also lamotrigine.

Please note that only common or more serious side effects have been discussed. Please consult the appropriate formularies for a complete list of adverse effects

Dosing

• The below initiation and escalation doses are only a guide and need to be individualised based on patient (age, weight, co-morbidities), disease (seizure type, frequency, duration) and medication (metabolism, interactions, side-effect profile) characteristics.

 

• Situations that require more careful consideration include children with higher weights, polytherapy, or multiple co-morbidities. Consultation with appropriate formularies or a paediatric neurologist may be required in specific circumstances.

Intravenous formulation can be used for the management of status epilepticus.

Commonly used regime

For Status Epilepticus:

• 15-20mg/kg given IV as a single loading dose.
• Additional respiratory support may be required with the higher loading doses, or if being used in conjunction with other sedative anti-epileptics.

For Seizures:  

• Target dose 1-5mg/kg/day in one or two doses. Drug elimination can change significantly over time in the neonatal period and early infancy as the liver enzymes mature. Single daily dosing can be used, especially in neonates and young infants due to the long half-life in this age group.
• Starting at lower doses and titrating up to the target dose over a period of 2-3 weeks can be effective in minimizing sedation. However, phenobarbitone is frequently used for the acute management of seizures and initiated at a usual target dose of 3-5mg/kg/day, and titrated based on therapeutic effect, side-effect profile, and serum drug levels. Certain patients with comorbidities such as chronic chest problems or bulbar dysfunction are particularly vulnerable. Care must be taken when used with other sedating drugs including midazolam.
• Maintenance dosing after an IV loading dose for status epilepticus is also usually around 3-5mg/kg/day, initiated 12-24 hours after the loading dose.
• Dosages per kilogram can only be used up to weights of 30-40kgs.

Preparations

• Oral solution 3mg/ml; Please note that some hospital pharmacies provide an oral solution with a higher concentration, and care needs to be taken when changing from an in-hospital to a community formulation.
• Tablet 30mg (scored).
• There is an intravenous form.

Monitoring

• There is a reasonable correlation between plasma levels of phenobarbitone and its therapeutic effect and/or toxicity.
• Pre-dose trough drug levels can be useful to assist with titration of dosing, to manage potential drug interactions, and to assess for toxicity.

Interactions | Precautions

• Phenobarbitone can cause respiratory depression when given as an IV loading dose and appropriate respiratory support may be required
• It is a strong enzyme inducer and may reduce the serum concentration of anti-epileptics such as carbamazepine and phenytoin. This needs to be taken into account both at the time of drug initiation as well as at the time of drug withdrawal.
• Drug levels of phenytoin and phenobarbitone can be unpredictable when used concurrently and monitoring of drug levels is important. Concentrations of either or both drugs can be reduced due to enzyme induction. Equally, elevated drug levels can also be seen because they compete for the same metabolic pathway.
• CYP450 enzyme inhibitors can increase levels of phenobarbitone.
• Phenobarbitone may also potentiate the sedative effects of other anti-epileptic medications, especially benzodiazepines.
• Withdrawal of phenobarbitone needs to be gradual, particularly with prolonged use, due to risk of seizures and other symptoms of withdrawal.