Phenytoin / Phenobarbital

What it is and how it works

Phenytoin stabilises neuronal membranes by blocking voltage-gated sodium channels and limiting repetitive firing, while phenobarbital enhances GABA-A receptor-mediated chloride currents and reduces glutamate excitation; together they raise the seizure threshold and limit seizure spread.

Indications

Generalised tonic-clonic and focal (partial) seizures in patients already stabilised on both components; fixed combinations are not recommended for initiating therapy.

Dosage and administration (summary)

Oral; dosing is individualised by the prescriber according to clinical response and plasma phenytoin concentrations, as the fixed ratio limits flexible titration.

Contraindications

Hypersensitivity to hydantoins or barbiturates, acute intermittent porphyria, severe respiratory depression, sinus bradycardia, sino-atrial block, second- or third-degree AV block and Adams-Stokes syndrome; concomitant delavirdine.

Warnings and precautions

Phenytoin has non-linear kinetics and a narrow therapeutic range; monitor plasma levels and signs of toxicity (nystagmus, ataxia). Serious skin reactions (SJS/TEN) may occur, particularly in carriers of HLA-B*1502; both drugs are potent enzyme inducers with many interactions, including reduced efficacy of hormonal contraceptives. Sedation, cognitive effects, dependence and suicidal ideation may occur; avoid abrupt withdrawal because of the risk of status epilepticus.

Pregnancy

Both components are associated with congenital malformations (fetal hydantoin syndrome) and neonatal bleeding; use only if benefit outweighs risk, with folic acid supplementation and vitamin K for the neonate.

Storage and supply

Store below 25 °C, protected from light and moisture.

Source: reference summary prepared from the EU SmPC/EPAR, BNF and WHO Model Formulary. The approved product information in Iran governs.