EPANUTIN Oral suspension Ref.[7331] Active ingredients: Phenytoin

For oral administration only.

Dosage

Dosage should be individualised as there may be wide interpatient variability in phenytoin serum levels with equivalent dosage. Epanutin should be introduced in small dosages with gradual increments until control is achieved or until toxic effects appear. In some cases serum level determinations may be necessary for optimal dosage adjustments – the clinically effective level is usually 10 mcg/mL-20 mcg/mL (40-80 micromoles/l) although some cases of tonic-clonic seizures may be controlled with lower serum levels of phenytoin. With recommended dosage a period of 7 to 10 days may be required to achieve steady state serum levels with Epanutin and changes in dosage should not be carried out at intervals shorter than 7 to 10 days. Maintenance of treatment should be the lowest dose of anticonvulsant consistent with control of seizures.

Epanutin Capsules, Oral Suspension and Infatabs

Epanutin Capsules contain phenytoin sodium whereas Epanutin Oral Suspension and Epanutin Infatabs contain phenytoin. Although 100 mg of phenytoin sodium is equivalent to 92 mg of phenytoin on a molecular weight basis, these molecular equivalents are not necessarily biologically equivalent. Physicians should therefore exercise care in those situations where it is necessary to change the dosage form and serum level monitoring is advised.

Posology

Adult Dosage for Seizures

Initially 3 to 4 mg/kg/day with subsequent dosage adjustment if necessary. For most adults a satisfactory maintenance dose will be 200 mg to 500 mg daily in single or divided doses. Exceptionally, a daily dose outside this range may be indicated. Dosage should normally be adjusted according to serum levels where assay facilities exist.

Dosing in Special Populations

Patients with Renal or Hepatic Disease

See section 4.4.

Adult Dosage for Trigeminal Neuralgia

The clinically effective dose has not been established in clinical trials. In adults, 300-500 mg daily given in divided doses has been reported in the literature. Dosing should be adjusted based on clinical response. Determination of serum phenytoin levels is advised. Levels of total phenytoin should not exceed 20 mcg/ml.

Elderly (over 65 years)

Phenytoin clearance may be decreased in elderly patients and lower or less frequent dosing may be required (see section 5.2 – Special Populations – Age). As with adults the dosage of Epanutin should be titrated to the patient’s individual requirements using the same guidelines. As older people tend to receive multiple drug therapies, the possibility of drug interactions should be borne in mind.

Paediatric population Dosage for Seizures

Initially, 5 mg/kg/day in two divided doses, with subsequent dosage individualised to a maximum of 300 mg daily. A recommended daily maintenance dosage is usually 4 mg/kg-8 mg/kg.

Neonates

The absorption of phenytoin following oral administration in neonates is unpredictable. Furthermore, the metabolism of phenytoin may be depressed. It is therefore especially important to monitor serum levels in the neonate.

The lethal dose in children is not known. The mean lethal dose for adults is estimated to be 2g to 5 g. The initial symptoms are nystagmus, ataxia and dysarthria. The patient then becomes comatose, the pupils are unresponsive and hypotension occurs followed by respiratory depression and apnoea. Bradycardia and asystole/cardiac arrest have been reported (see Section 4.4). Death is due to respiratory and circulatory depression.

There are marked variations among individuals with respect to phenytoin serum levels where toxicity may occur. Nystagmus on lateral gaze usually appears at 20 mg/l, and ataxia at 30 mg/l, dysarthria and lethargy appear when the serum concentration is greater than 40 mg/l, but a concentration as high as 50 mg/l has been reported without evidence of toxicity.

As much as 25 times therapeutic dose has been taken to result in serum concentration over 100 mg/l (400 micromoles/l) with complete recovery. Irreversible cerebellar dysfunction and atrophy have been reported.

Treatment

Treatment is non-specific since there is no known antidote. If ingested within the previous 4 hours the stomach should be emptied. If the gag reflex is absent, the airway should be supported. Oxygen, and assisted ventilation may be necessary for central nervous system, respiratory and cardiovascular depression. Haemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been utilised in the treatment of severe intoxication in children.

In acute overdosage the possibility of the presence of other CNS depressants, including alcohol, should be borne in mind.

Shelf life: 3 years.

Do not store above 25°C.

Amber glass bottle with 3 piece tamper evident child resistant closure fitted with a polyethylene faced liner containing 125 ml or 500 ml. Finished pack will either have a label/leaflet or be enclosed in a carton with a separate PIL.

Not all pack sizes may be marketed.

Shake well before use.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.