Status epilepticus, severe head injury

In a patient having continuous seizure activity, as compared to the more common rapidly recurring seizures, i.e. serial epilepsy, injection of intravenous diazepam or a short acting barbiturate is recommended because of their rapid onset of action, prior to administration of Epanutin.

Following the use of diazepam in patients having continuous seizures and in the initial management of serial epilepsy a loading dose of Epanutin 10 mg/kg-15 mg/kg should be injected slowly intravenously, at a rate not exceeding 50 mg per minute in adults (this will require approximately 20 minutes in a 70 kg patient). The loading dose should be followed by maintenance doses of 100 mg orally or intravenously every 6 to 8 hours.

Recent work in neonates has shown that absorption of phenytoin is unreliable after oral administration, but a loading dose of 15 mg/kg-20 mg/kg of Epanutin intravenously will usually produce serum concentrations of phenytoin within the generally accepted therapeutic range (10 mcg/mL-20 mcg/mL).

The drug should be injected slowly intravenously at a rate of 1-3 mg/kg/min.

Determination of phenytoin serum levels is advised when using Epanutin in the management of status epilepticus and in the subsequent establishing of maintenance dosage. The clinically effective level is usually 10 mcg/mL–20 mcg/mL although some cases of tonic-clonic seizures may be controlled with lower serum levels of phenytoin.

Intramuscular administration should not be used in the treatment of status epilepticus because the attainment of peak plasma levels may require up to 24 hours.

Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. Parenteral Epanutin is suitable for use as long as it remains free of haziness and precipitate. Upon refrigeration or freezing a precipitate might form; this will dissolve again after the solution is allowed to stand at room temperature. The product is still suitable for use. Only a clear solution should be used. A faint yellow colouration may develop, however, this has no effect on the potency of this solution.

There is a relatively small margin between full therapeutic effect and minimally toxic doses of this drug. Optimum control without clinical signs of toxicity occurs most often with serum levels between 10 mcg/mL and 20 mcg/mL (40-80 micromoles/l).

Because of the risk of local toxicity, intravenous phenytoin should be injected slowly directly into a large vein through a large-gauge needle or intravenous catheter.

Each injection or infusion of intravenous Epanutin should be preceded and followed by an injection of sterile saline through the same needle or catheter to avoid local venous irritation due to alkalinity of the solution (see section 4.4. Local Toxicity (including Purple Glove Syndrome)).

For infusion administration the parenteral phenytoin should be diluted in 50 ml-100 ml of normal saline, with the final concentration of phenytoin in the solution not exceeding 10 mg/ml. Administration should commence immediately after the mixture has been prepared and must be completed within one hour (the infusion mixture should not be refrigerated). An in-line filter (0.22 microns-0.50 microns) should be used.

The diluted form is suitable for use as long as it remains free of haziness and precipitate.

Parenteral Epanutin should neither be mixed with other drugs nor be added to dextrose or dextrose-containing solutions due to the potential for precipitation of phenytoin acid.

Continuous monitoring of the electrocardiogram and blood pressure is essential. Cardiac resuscitative equipment should be available. The patient should be observed for signs of respiratory depression. If administration of intravenous Epanutin does not terminate seizures, the use of other measures, including general anaesthesia, should be considered.