Phenobarbitone is a long-acting barbiturate with potent sedative, hypnotic, and anticonvulsant properties. It is a first-generation antiepileptic drug (AED) that works primarily by enhancing the inhibitory effects of GABA in the central nervous system. In the Indian context, it remains a critical, low-cost option for the management of generalized tonic-clonic and focal seizures, and for status epilepticus, despite its significant side effect profile and potential for dependence. Its use is strictly regulated under Schedule H1 and Schedule G of the Drugs and Cosmetics Act.
Adult: Epilepsy: Initial: 60-120 mg/day orally, given as a single dose at bedtime or in 2-3 divided doses. Maintenance: 60-180 mg/day. Status Epilepticus: 10-20 mg/kg by slow IV injection, not exceeding 100 mg/minute.
Note: Oral: Take at the same time each day, usually at bedtime to minimize daytime sedation. Can be taken with or without food. Do not crush or chew sustained-release formulations. IV: For status epilepticus, administer slowly (not exceeding 100 mg/min) with resuscitation equipment available. IM: Deep intramuscular injection is possible but painful and absorption is erratic.
Phenobarbitone acts as a positive allosteric modulator at the GABA-A receptor complex. It binds to a distinct barbiturate site, increasing the duration of chloride channel opening events when GABA binds. This enhances GABA-mediated inhibitory neurotransmission, leading to neuronal hyperpolarization and reduced neuronal excitability. At higher doses, it can directly activate the GABA-A receptor.
Pregnancy: Pregnancy Category D (US FDA). Known teratogen (risk of congenital malformations like cleft lip/palate, cardiac defects). Also associated with neonatal withdrawal syndrome, hemorrhagic disease of the newborn (due to vitamin K depletion), and possible long-term neurodevelopmental effects. Use only if clearly needed and benefits outweigh risks. Folic acid supplementation (5 mg/day) is recommended. Monitor newborn closely for withdrawal.
Driving: STRONGLY ADVISED AGAINST. Causes significant drowsiness, dizziness, and impaired coordination and judgment, increasing accident risk.
| Warfarin, Acenocoumarol | Phenobarbitone induces metabolism, decreasing anticoagulant effect. Requires frequent INR monitoring and dose adjustment. | Major |
| Oral Contraceptives, Levonorgestrel | Reduces contraceptive efficacy due to enzyme induction, leading to breakthrough bleeding and risk of pregnancy. Alternative non-hormonal methods advised. | Major |
| Phenytoin, Carbamazepine, Valproate | Complex bidirectional interactions. Phenobarbitone can increase or decrease levels of other AEDs. Monitoring of serum levels is essential. | Major |
| Doxycycline, Chloramphenicol | Reduced antibiotic efficacy due to increased metabolism. | Moderate |
| Digoxin | Decreased digoxin serum levels. | Moderate |
| Theophylline | Decreased theophylline levels, reducing bronchodilator effect. | Moderate |
| Alcohol, Benzodiazepines, Opioids | Additive CNS and respiratory depression. Potentially fatal. | Major |
| Valproic Acid | Increases phenobarbitone levels by inhibiting its metabolism, leading to toxicity. | Major |
| CYP2C9/CYP2C19 Inhibitors (e.g., Fluconazole) | Increase phenobarbitone levels, risk of toxicity. | Moderate |
Same composition (Phenobarbitone (60mg)), different brands: