Phenytoin Sodium

Diphedan is an anticonvulsant which is used in the treatment of status epilepticus of grandmal type. It may also be used in the prevention and treatment of seizures occur during neurosurgery.

Phenytoin acts as an anticonvulsant by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses; thus stabilising neuronal membranes and decreasing seizure activity. It acts as an antiarrhythmic by extending the effective refractory period and suppressing ventricular pacemaker automaticity, shortening action potential in the heart.

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).

Effects with other sedative drugs or ethanol may be potentiated. Enhances toxic effects of paracetamol, lithium. Increased risk of osteomalacia with acetazolamide. Decreased serum levels/effects with acyclovir, antineoplastics, benzodiazeines, ciprofloxacin, CYP2C9 inducers (e.g. carbamazepine), CYP2C19 inducers (e.g. rifampin), folic acid, vigabatrin. Increased serum concentrations with allopurinol, capecitabine, cimetidine, CYP2C9 inhibitors (e.g. fluconazole), CYP2C19 inhibitors (e.g. delavirdine), disulfiram, methylphenidate, metronidazole, omeprazole, SSRI, trazodone, trimethoprim. Increases metabolism of antiarrhythmics, anticonvulsants, antipsychotics, beta-blockers, calcium channel blockers, chloramphenicol, corticosteroids, doxycycline, oestrogens, HMG-CoA reductase inhibitors, methadone, theophylline, TCAs. Decreases levels/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, topiramate. Increases levels/effect of dopamine, ticlopidine. Valproic acid may displace phenytoin from binding sites; and affect phenytoin serum concentrations. Transiently increases the hypothrombinaemia response to warfarin initially, followed by an inhibition of the response.

Phenytoin is contraindicated in those patients who are hyper sensitive to phenytoin and hydentoins.

Skin rashes may occasionally develop but they disappear when treatment is discontinued. Therapy may then be resumed with lower doses. Insomnia, slurred speech, transient nervousness, dizziness, headache may also occur.

In prolonged treatment periodic checking of the blood is advisable. Dose should be discontinued if skin rashes appears. Hyperglycemia resulting from the drug inhibitory effects on insulin release has been reported. It should be used with caution in pregnancy and in nursing mother.

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.