DBL PHENYTOIN INJECTION BP 50 MG/ML [SIN08183P]

Product Info

DBL PHENYTOIN INJECTION BP 50 MG/ML

[SIN08183P]

4.1 Therapeutic Indications

For the control of status epilepticus, tonic-clonic (grand mal), psychomotor seizures and the prevention of seizures occurring during or following neurosurgery. Phenytoin will prevent or effectively decrease the incidence and severity of convulsive seizures in a high percentage of cases, with patients exhibiting little tendency to become resistant to its action. Besides its effectiveness in controlling seizures, phenytoin frequently improves the mental condition and outlook of epileptic patients.

It has also been used in the treatment of certain cardiac arrhythmias, particularly in those patients who do not respond to conventional antiarrhythmic agents or to cardioversion.

Phenytoin serum level determinations may be necessary for optimal dosage adjustments (see section 4.2 Dose and Method of Administration).

4.2 Dose and Method of Administration

Dosage

Status epilepticus: For the control of status epilepticus in adults, a loading dose of 10 to 15 mg/kg should be administered slowly intravenously, at a rate not exceeding 50 mg/min. 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.

For neonates and children, a loading dose of 10 to 20 mg/kg intravenously will usually provide a plasma concentration of phenytoin within the generally accepted therapeutic range (10 to 20 micrograms/mL). The drug should be administered intravenously at a rate not exceeding 1 to 3 mg/kg/min, maximum of 50 mg/min, (see section 4.4 Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Children tend to metabolise phenytoin more rapidly than adults, which may affect dosage regimens. Therefore, serum level monitoring may be particularly beneficial in such cases.

In the treatment of status epilepticus, an intravenous benzodiazepine such as diazepam or an intravenous short acting barbiturate, are usually given initially for the rapid control of seizures and are then followed by the slow intravenous administration of phenytoin.

Intramuscular administration of phenytoin is unsuitable for the emergency treatment of status epilepticus due to very slow and erratic absorption from the intramuscular site.

Intra-arterial administration must be avoided in view of the high pH of the preparation.

Dosage should be individualised to obtain maximum benefit. In some cases, serum blood level determinations may be necessary for optimal dosage adjustments. Serum levels between 10 and 20 micrograms/mL (40 to 80 micromoles/L) are considered to be clinically effective. With the recommended dosage, a period of at least 7 to 10 days may be required to achieve therapeutic blood levels of phenytoin unless therapy is initiated with a loading dose. After the initial dose has been prescribed, plasma levels should be determined and the dosage adjusted if necessary to obtain a level in the therapeutic range; 10 to 20 micrograms/mL (40 to 80 micromoles/L).

Neurosurgery: For the prevention of seizures during or following neurosurgery, cautious intravenous administration of 250 mg every six to twelve hours is recommended until oral dosage is possible. Plasma levels should be monitored to ensure optimal efficacy and to minimise toxicity. Phenytoin should not be given by intramuscular injection for the prevention of seizures following neurosurgery.

Cardiac arrhythmias: Phenytoin sodium can be useful in ventricular arrhythmias, especially those due to digitalis. Although not a cardiac depressant, it has a positive inotropic effect and enhances conduction, though it generally decreases automaticity. The recommended dosage is one intravenous injection of DBL Phenytoin Injection of 3 to 5 mg/kg bodyweight initially, repeating if necessary.

Because there is approximately an 8% increase in drug content in the free form over that of the sodium salt, dosage adjustments and serum level monitoring may be necessary when switching from a product formulated with the free acid to a product formulated with the sodium salt to the form or vice versa.

Continuous monitoring of the electrocardiogram and blood pressure is essential. The patient should be observed for signs of respiratory depression. Determination of phenytoin plasma levels is advised when using phenytoin in the management of status epilepticus and the subsequent establishment of maintenance dosage. Cardiac resuscitative equipment should be available.

Method of Administration

DBL Phenytoin Injection must be administered slowly. Intravenous administration should not exceed 50 mg/min in adults. In neonates and children, the drug should be administered at a rate not exceeding 1 to 3 mg/kg/min, maximum of 50 mg/min.

Dilution of DBL Phenytoin Injection into intravenous infusion is not recommended due to lack of solubility and resultant precipitation.

The solution is suitable for use as long as it remains free of haziness and precipitate. A precipitate might form if the product has been kept in a refrigerator or freezer. This precipitate will dissolve if allowed to stand at room temperature. The product will then be suitable for use.

DBL Phenytoin Injection should be injected slowly and directly into a large vein through a large-gauge needle or intravenous catheter. Prior to the administration, the patency of the IV catheter should be tested with a flush of sterile saline. Each injection should be followed by an injection of sodium chloride intravenous infusion 0.9% through the same needle or catheter to avoid local venous irritation due to the alkalinity of the solution. Continuous infusion should be avoided.

Product is for one dose in one patient only. Discard any remaining contents.

4.3 Contraindications

Phenytoin is contraindicated in patients with:

1. Known hypersensitivity to phenytoin, or any of the excipients (see section 6.1 List of Excipients – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), or other hydantoins.

2. Sinus bradycardia, sino-atrial block, second and third degree AV block or Stokes Adams syndrome due to its effect on ventricular automaticity.

Co-administration of phenytoin with delavirdine is contraindicated due to potential for loss of virologic response and possible resistance to delavirdine or to the class of non-nucleoside reverse transcriptase inhibitors.