Section 01 · Monograph
Phenobarbital
Reviewed Nov 2026FDA label
LuminalBarbiturate
- Forms
- Tab: 15, 30, 60, 100mg | Elixir: 20mg/5mL | IV: 65, 130mg/mL
- Dose
- 60-200mg/day
- MOA
- ↑GABA-A Cl- channel open duration
Black Box Warning
- May be habit-forming — tolerance and psychological/physical dependence can develop with continued use; abrupt discontinuation after prolonged use may precipitate withdrawal symptoms including delirium, seizures, and death
Indications
- Anticonvulsant for generalized tonic-clonic and partial seizuresFDA-labeled
- Management of status epilepticus (IV formulation)FDA-labeled
- SedativeFDA-labeled
Mechanism of Action
- Enhances GABA-A receptor–mediated chloride influx by prolonging channel open duration, producing broad CNS depression and raising seizure threshold
- At higher concentrations can directly activate GABA-A receptors and inhibit glutamate-mediated excitatory transmission
Full Dosing
Adult / usual
- Status epilepticus (IV): weight-based loading per institutional protocol, given slowly with continuous respiratory and hemodynamic monitoring
- Sedation: 30–120mg/day in 2–3 divided doses; hypnotic use 100–200mg at bedtime
- Therapeutic serum concentrations for seizure control are generally cited in the range of roughly 15–40mcg/mL
- Taper gradually over weeks when discontinuing after prolonged use to avoid withdrawal seizures
Pediatric
- Anticonvulsant (adults): approximately 60–200mg/day PO, often as a single bedtime dose or divided; pediatric ~3–6mg/kg/day
Contraindications
- Hypersensitivity to barbiturates
- History of porphyria
- Marked hepatic impairment or severe respiratory disease with dyspnea or airway obstruction
- Prior history of sedative-hypnotic addiction (relative)
Drug Interactions
- Potent inducer of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP3A4, and UGT enzymes — reduces efficacy of hormonal contraceptives, warfarin, corticosteroids, doxycycline, and other AEDs
- Additive CNS and respiratory depression with alcohol, opioids, benzodiazepines, and other sedative-hypnotics
- Complex bidirectional interactions with other AEDs (e.g., phenytoin, valproate) affecting mutual serum levels
Adverse Effects
- Sedation, drowsiness, and cognitive dulling — most prominent early in treatment
- Paradoxical hyperactivity or agitation, particularly in children and the elderly
- Respiratory depression, especially with other CNS depressants or in overdose
- Physical dependence and withdrawal seizures with abrupt discontinuation after prolonged use
- Rare: Stevens-Johnson syndrome/TEN, megaloblastic anemia (folate-responsive), osteomalacia with long-term use
- Connective tissue changes (e.g., Dupuytren's contracture, frozen shoulder) reported with chronic use
Monitoring Parameters
- Serum phenobarbital concentration
- CBC and folate status, and periodic bone density with long-term therapy
- Respiratory status, especially when combined with other CNS depressants
- Signs of withdrawal during dose tapering
- Mood, behavior, and cognitive effects, particularly in children
Pregnancy & Lactation
- Crosses the placenta; associated with increased risk of congenital malformations and neonatal withdrawal or hemorrhagic disease of the newborn (vitamin K prophylaxis recommended)
- Excreted into breast milk and can cause sedation in breastfed infants — monitor closely