Phenobarbital

• Epilepsy:
• Generalized tonic-clonic seizures
• Partial seizures
• Febrile seizures in children (adjunctive therapy)
• Sedation:
• Preoperative sedation
• Sedation in intensive care settings
• Status Epilepticus:
• Second-line treatment after benzodiazepines
• Off-label Uses:
• Neonatal seizures
• Adjunctive management of alcohol withdrawal seizures

• Route: Oral, intravenous (IV), intramuscular (IM)
• Adults:
• Oral initial dose: 60–200 mg daily in divided doses (once to thrice daily)
• Maintenance dose: 60–180 mg daily adjusted by clinical response and serum levels
• IV/IM loading dose for status epilepticus: 15–20 mg/kg slow IV infusion (maximum 1000 mg); maintenance 1–3 mg/kg/day
• Pediatrics:
• Initial oral dose: 3–5 mg/kg/day divided into 1–3 doses
• Maintenance dose: 3–6 mg/kg/day adjusted per clinical response and serum levels
• Elderly:
• Start with lower doses; monitor for sedation and cognitive effects; adjust dose accordingly
• Special Populations:
• Hepatic or renal impairment: Use caution and adjust dosage as needed with monitoring
• Duration: Long-term therapy for epilepsy; short-term for sedation or acute seizure control as indicated

Phenobarbital is a long-acting barbiturate that potentiates gamma-aminobutyric acid (GABA) neurotransmission by binding to the GABA_A receptor complex. This increases the duration of chloride channel opening, leading to neuronal hyperpolarization and decreased excitability. The resulting inhibition of abnormal neuronal firing reduces seizure activity and produces sedative effects.

• Absorption: Well absorbed orally; peak plasma concentrations in 1–4 hours
• Distribution: Widely distributed; crosses blood-brain barrier and placenta; volume of distribution approximately 0.5–0.9 L/kg
• Metabolism: Hepatic metabolism primarily via CYP2C9 and CYP2C19
• Half-life: 53–118 hours, variable with age and liver function
• Excretion: Primarily renal excretion of metabolites and unchanged drug

• Pregnancy: FDA Category D; associated with risk of congenital malformations including fetal hydantoin syndrome; use only if benefits justify risks
• Lactation: Excreted in breast milk; potential for sedation in nursing infants; caution advised

• Class: Antiepileptic drug (AED)
• Subclass: Barbiturate

• Hypersensitivity to phenobarbital or other barbiturates
• Severe respiratory insufficiency
• Severe hepatic impairment
• Porphyria
• History of addiction to sedative-hypnotics

• Risk of respiratory depression, especially with concomitant CNS depressants
• Potential for physical dependence, tolerance, and withdrawal seizures on abrupt discontinuation
• Monitor liver and kidney function during prolonged use
• Caution in elderly, debilitated patients, and those with psychiatric disorders
• Risk of suicidal ideation; monitor mental health
• May impair cognitive and motor function; caution when operating machinery or driving

• Common: Sedation, drowsiness, dizziness, cognitive impairment, ataxia, nausea
• Serious: Respiratory depression, hypotension (especially IV), Stevens-Johnson syndrome, blood dyscrasias (e.g., agranulocytosis), hepatotoxicity
• Rare: Paradoxical excitation, dependence, withdrawal seizures

• Induces CYP450 enzymes (CYP3A4, CYP2C9, CYP2C19), decreasing efficacy of various drugs (oral contraceptives, warfarin, corticosteroids)
• Additive CNS depression with alcohol, benzodiazepines, opioids, and other sedatives
• May reduce effectiveness of other antiepileptics or anticoagulants
• Valproate may increase phenobarbital serum levels

• Therapeutic drug monitoring recommended to maintain serum levels between 15–40 mcg/mL for optimal seizure control and minimal toxicity
• Avoid abrupt discontinuation to prevent withdrawal seizures
• Generally reserved as a second- or third-line agent for epilepsy due to sedative side effects and availability of newer AEDs
• Continued caution in pregnancy; folic acid supplementation advised

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture
• Keep container tightly closed
• Keep out of reach of children