Phenytoin is an anticonvulsant used in the treatment of generalized tonic-clonic status epilepticus. It is also used for the prevention and management of seizures occurring during neurosurgery.

Phenytoin acts as an anticonvulsant by stabilizing neuronal membranes. It decreases neuronal excitability by reducing sodium ion influx and/or increasing sodium ion efflux across cell membranes in the motor cortex during nerve impulse generation. This leads to suppression of repetitive neuronal firing and reduced seizure activity. It also exhibits antiarrhythmic properties by prolonging the effective refractory period and suppressing ventricular pacemaker automaticity, thereby shortening the cardiac action potential.

Adults: 200 mg (2 tablets) daily increased to 400 mg (Maximum 600 mg/day) daily in divided doses or 3-4 mg/kg daily in divided doses. For adult patients (who have received no previous medication) the treatment is one tablet three times daily or as directed by the physician.

Children: Initially, 5 mg/kg per day in two or three equally divided dosage, with subsequent dosage individualized to maximum 300 mg daily. A recommended daily maintenance dosage is usually 4 to 8 mg/kg. Children over 6 years require the minimal adult dose (300 mg/day).

The effects of Phenytoin may be enhanced when used with other sedatives or ethanol (alcohol). It may also increase the toxic effects of paracetamol and lithium. There is an increased risk of osteomalacia when used with acetazolamide. Serum levels and effects of Phenytoin may be reduced by acyclovir, antineoplastic agents, benzodiazepines, ciprofloxacin, CYP2C9 inducers (e.g., carbamazepine), CYP2C19 inducers (e.g., rifampin), folic acid, and vigabatrin. Serum concentrations of Phenytoin may be increased by allopurinol, capecitabine, cimetidine, CYP2C9 inhibitors (e.g., fluconazole), CYP2C19 inhibitors (e.g., delavirdine), disulfiram, methylphenidate, metronidazole, omeprazole, SSRIs, trazodone, and trimethoprim. Phenytoin increases the metabolism of antiarrhythmics, anticonvulsants, antipsychotics, beta-blockers, calcium channel blockers, chloramphenicol, corticosteroids, doxycycline, estrogens, HMG-CoA reductase inhibitors, methadone, theophylline, and tricyclic antidepressants. It may decrease the levels or effects of clozapine, ciclosporin, tacrolimus, CYP2B6 substrates (e.g., bupropion, selegiline), CYP2C8 substrates (e.g., amiodarone), CYP2C9 substrates (e.g., celecoxib), CYP2C19 substrates (e.g., citalopram), CYP3A4 substrates (e.g., benzodiazepines), digoxin, itraconazole, levodopa, neuromuscular blocking agents, thyroid hormones, and topiramate. It may increase the effects of dopamine and ticlopidine. Valproic acid may displace phenytoin from protein-binding sites and alter its serum concentration. Phenytoin may initially increase the hypoprothrombinemic effect of warfarin, followed by a later inhibition of response.

Phenytoin is contraindicated in patients with known hypersensitivity to phenytoin or other hydantoin derivatives.

Skin rashes may occur occasionally and usually disappear after discontinuation of treatment. Therapy may be restarted at a lower dose. Other possible side effects include insomnia, slurred speech, transient nervousness, dizziness, and headache.

During long-term therapy, periodic blood monitoring is recommended. The drug should be discontinued if skin rash develops. It may cause hyperglycemia by inhibiting insulin release. It should be used with caution during pregnancy and breastfeeding.

Adjunct anti-epileptic drugs

Store below 30°C, protected from light and moisture. Keep out of reach of children.