Cerebyx is indicated for short-term parenteral administration when other means of phenytoin administration are unavailable, inappropriate or deemed less advantageous. The safety and effectiveness of Cerebyx in this use has not been systematically evaluated for more than 5 days.

Cerebyx can be used for the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. It can also be substituted, short-term, for oral phenytoin.

The dose, concentration in dosing solutions, and infusion rate of IV Cerebyx is expressed as phenytoin sodium equivalents (PE) to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. Cerebyx should always be pre scribed and dispensed in phenytoin sodium equivalent units (PE). Cerebyx has important differences in administration from those for parenteral phenytoin sodium (see below).

Products with particulate matter or discoloration should not be used. Prior to IV infusion, dilute Cerebyx in 5% dextrose or 0.9% saline solution for injection to a concentration ranging from 1.5 to 25 mg PE/mL.

Status Epilepticus

• The loading dose of Cerebyx is 15 to 20 mg PE/kg administered at 100 to 150 mg PE/min.
• Because of the risk of hypotension, fosphenytoin should be administered no faster than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of Cerebyx infusions.
• Because the full antiepileptic effect of phenytoin, whether given as Cerebyx or parenteral phenytoin, is not immediate, other measures, including concomitant administration of an IV benzodiazepine, will usually be necessary for the control of status epilepticus.
• The loading dose should be followed by maintenance doses of Cerebyx, or phenytoin either orally or parenterally.

If administration of Cerebyx does not terminate seizures, the use of other anticonvulsants and other appropriate measures should be considered.

IM Cerebyx should not be used in the treatment of status epilepticus because therapeutic phenytoin concentrations may not be reached as quickly as with IV administration. If IV access is impossible, loading doses of Cerebyx have been given by the IM route for other indications.

Nonemergent Loading and Maintenance Dosing

The loading dose of Cerebyx is 10 - 20 mg PE/kg given IV or IM. The rate of administration for IV Cerebyx should be no greater than 150 mg PE/min. Continuous monitoring of the electrocardiogram, blood pressure, and respiratory function is essential and the patient should be observed throughout the period where maximal serum phenytoin concentrations occur, approximately 10 to 20 minutes after the end of Cerebyx infusions.

The initial daily maintenance dose of Cerebyx is 4 - 6 mg PE/kg/day.

IM or IV Substitution For Oral Phenytoin Therapy

Cerebyx can be substituted for oral phenytoin sodium therapy at the same total daily dose.

Dilantin capsules are approximately 90% bioavailable by the oral route. Phenytoin, supplied as Cerebyx, is 100% bioavailable by both the IM and IV routes. For this reason, plasma phenytoin concentrations may increase modestly when IM or IV Cerebyx is substituted for oral phenytoin sodium therapy.

The rate of administration for IV Cerebyx should be no greater than 150 mg PE/min.

In controlled trials, IM Cerebyx was administered as a single daily dose utilizing either 1 or 2 injection sites. Some patients may require more frequent dosing.

Dosing in Special Populations

Patients with Renal or Hepatic Disease: Due to an increased fraction of unbound phenytoin in patients with renal or hepatic disease, or in those with hypoalbuminemia, the interpretation of total phenytoin plasma concentrations should be made with caution (see CLINICAL PHARMACOLOGY: Special Populations). Unbound phenytoin concentrations may be more useful in these patient populations. After IV Cerebyx administration to patients with renal and/or hepatic disease, or in those with hypoalbuminemia, fosphenytoin clearance to phenytoin may be increased without a similar increase in phenytoin clearance. This has the potential to increase the frequency and severity of adverse events (see PRECAUTIONS).

Elderly Patients: Age does not have a significant impact on the pharmacokinetics of fosphenytoin following Cerebyx administration. Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required.

Pediatric: The safety of Cerebyx in pediatric patients has not been established.

Cerebyx Injection is supplied as follows:

10 mL per vial — Each vial contains fosphenytoin sodium 750 mg equivalent to 500 mg of phenytoin sodium:

N 0071-4008-10. Packages of 10.

2 mL per vial — Each vial contains fosphenytoin sodium 150 mg equivalent to 100 mg of phenytoin sodium:

N 0071-4007-05. Packages of 25.

Both sizes of vials contain Tromethamine, USP (TRIS), Hydrochloric Acid, NF, or Sodium Hydroxide, NF, and Water for Injection, USP.

Cerebyx should always be prescribed in phenytoin sodium equivalent units (PE) (see DOSAGE AND ADMINISTRATION).

Storage

Store under refrigeration at 2°C to 8°C (36°F to 46°F). The product should not be stored at room temperature for more than 48 hours. Vials that develop particulate matter should not be used.

Warner-Lambert Co. Revised June 2002. Distributed by: AParke-Davis, Division of Pfizer Inc, NY, NY 10017. MADE IN IRELAND. Marketed by Eisai Inc., Teaneck, NJ 07666. FDA revision date: 1/2/2002

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