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

Commonly used regime

Local protocols may vary from those stated below.

For status epilepticus in children > 1 month of age:

• 15-20mg/kg given IV/IO as a single loading dose.
• Maximum 1g IV/IO
• Additional respiratory support may be required with the higher loading doses, or if being used in conjunction with other sedative anti-epileptics.

For status epilepticus in neonates

• Birth (at term) – 1 month, IV 20 mg/kg

For seizures in the non-acute setting 

• 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.
• When phenobarbitone is used for the acute management of seizures, it can be 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.

Formulary

• eMIMS

CNS depression and sedation are the most common side effects, particularly when the drug is initiated, which 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, including carbamazepine, phenytoin and also lamotrigine.

All anti-seizure medications are potentially teratogenic and this is often dose related.

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.

• 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-seizure medications 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 together, secondary to enzyme induction (reduced levels) or because they compete for the same metabolic pathway (increased levels). Monitoring of levels is important in this context.
• 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.
• 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. 

• PBS (Pharmaceutical Benefits Scheme)
• MIMS (Monthly Index of Medical Specialties)
• AMH (Australian Medicines Handbook)