phenobarbital
Brand: Luminal
Beers Criteria TDM Required Prototype: diazepam
Drug Class: antiepileptic drug / barbiturate
Drug Family: antiepileptic
Subclass: barbiturate GABA-A potentiator
Organ Systems: cns
Mechanism of Action
Binds the barbiturate site on GABA-A receptors, increasing the DURATION of chloride channel opening (distinct from benzodiazepines which increase frequency). At high doses, can directly gate the channel independently of GABA. Profound CNS depression; also a potent inducer of CYP enzymes.
GABA-A receptor (barbiturate site — beta subunit)AMPA glutamate receptors (blockade at high doses)
Indications
- epilepsy (focal and generalized seizures)
- neonatal seizures (drug of choice)
- status epilepticus (IV)
- febrile seizures (prophylaxis — historical; less preferred now)
- alcohol/benzodiazepine withdrawal (off-label)
- sedation (perioperative)
Contraindications
- porphyria
- severe hepatic impairment
- severe respiratory depression
Adverse Effects
Common
- sedation
- cognitive impairment
- nystagmus
- ataxia
- hyperactivity (children)
- rash
Serious
- respiratory depression (overdose)
- physical dependence and withdrawal (potentially fatal)
- cognitive decline with long-term use
- cardiovascular depression (overdose)
Pharmacokinetics (ADME)
| Absorption | oral or IV; bioavailability ~80% |
| Distribution | 20–45% protein bound |
| Metabolism | hepatic via CYP2C9, CYP2C19; potent enzyme inducer |
| Excretion | renal (25% unchanged) |
| Half-life | 53–140 hours (adult); 45–100 hours (neonate — longer) |
| Onset | 15–30 minutes (IV) |
| Peak | varies |
| Duration | 4–10 hours (sedation); continuous (AED effect) |
| Protein Binding | 20–45% |
| Vd | 0.5–0.9 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| oral contraceptives | potent CYP3A4 induction reduces OCP levels | major |
| warfarin | CYP2C9 induction reduces warfarin levels; dose adjustment required when adding or stopping phenobarbital | major |
| many CNS depressants | additive CNS/respiratory depression | major |
Nursing Considerations
- Therapeutic level for seizures: 15–40 mcg/mL (total serum); toxicity usually occurs at >40–60 mcg/mL.
- Neonatal seizures: phenobarbital remains first-line; monitor respiratory function closely in neonates who require high doses.
- Tolerance to sedation develops over weeks but tolerance to anticonvulsant effects is minimal.
- Abrupt discontinuation after long-term use can cause life-threatening withdrawal seizures; taper slowly (over months).
Clinical Pearls
- Phenobarbital is the world's most widely used AED due to its low cost and global availability; it remains first-line in resource-limited settings despite its side effect profile.
- As a neonatal seizure treatment, phenobarbital has unique advantages: IV administration, broad efficacy, and extensive safety data in this fragile population.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.