Phenobarbitone | Epilepsy clinician handbook
- A long-acting barbiturate anti-epileptic that increases GABA-mediated inhibition via modulation of post-synaptic chloride channels.
- Effective for both focal and generalized seizures and can be used for the management of status epilepticus.
- It is often used as the first line agent for status epilepticus in the neonatal period.
Possible side effects
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.
Interactions and 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-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.