CEREBYX

CEREBYX- fosphenytoin sodium injection, solution
Pfizer Laboratories Div Pfizer Inc

1 INDICATIONS AND USAGE

CEREBYX is indicated for the treatment of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. CEREBYX can also be substituted, short-term, for oral phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible [see Dosage and Administration (2.4) and Warnings and Precautions (5.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Instructions to Avoid Dosing Errors

Use caution when administering CEREBYX because of the risk of dosing errors [see Warnings and Precautions (5.1)].

Phenytoin Sodium Equivalents (PE)

The dose, concentration, and infusion rate of CEREBYX should always be expressed as phenytoin sodium equivalents (PE). There is no need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses. CEREBYX should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). The amount and concentration of fosphenytoin is always expressed in terms of mg of phenytoin sodium equivalents (mg PE).

Concentration of 50 mg PE/mL

Do not confuse the concentration of CEREBYX with the total amount of drug in the vial.

Errors, including fatal overdoses, have occurred when the concentration of the vial (50 mg PE/mL) was misinterpreted to mean that the total content of the vial was 50 mg PE. These errors have resulted in two- or ten-fold overdoses of CEREBYX since each of the vials actually contains a total of 100 mg PE (2 mL vial) or 500 mg PE (10 mL vial). Ensure the appropriate volume of CEREBYX is withdrawn from the vial when preparing the dose for administration. Attention to these details may prevent some CEREBYX medication errors from occurring.

2.2 Preparation

Prior to intravenous (IV) infusion, dilute CEREBYX in 5% Dextrose Injection or 0.9% Sodium Chloride Injection to a concentration ranging from 1.5 to 25 mg PE/mL. The maximum concentration of CEREBYX in any solution should be 25 mg PE/mL. When CEREBYX is given as an IV infusion, CEREBYX needs to be diluted and should only be administered at a rate not exceeding 150 mg PE/min.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

For single-dose only. After opening, any unused product should be discarded.

2.3 Status Epilepticus

• Because of the risk of hypotension and cardiac arrhythmias, the rate of administration for IV CEREBYX should be no greater than 150 mg PE/min in adults and 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) in pediatric patients [see Warnings and Precautions (5.2)]. 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 either CEREBYX or phenytoin [see Dosage and Administration (2.4)].
• If administration of CEREBYX does not terminate seizures, the use of other anticonvulsants and other appropriate measures should be considered.

Adult and Pediatric Status Epilepticus Dosing:

Table 1. Status Epilepticus Loading Dosages

Population	Dosage	Infusion rate
Adult	15 mg PE/kg to 20 mg PE/kg	100 mg PE/min to 150 mg PE/min, do not exceed a maximum rate of 150 mg PE/min
Pediatric (Birth to less than 17 years of age)	15 mg PE/kg to 20 mg PE/kg	2 mg PE/kg/min, or 150 mg PE/min, whichever is slower

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

Intramuscular administration of CEREBYX should ordinarily not be used in pediatric patients. When IV access has been impossible, loading doses of CEREBYX have been given by the IM route.

2.4 Non-emergent Loading and Maintenance Dosing

• Because of the risk of hypotension and cardiac arrhythmias, the rate of administration for IV CEREBYX should be no greater than 150 mg PE/min in adults. For loading doses in pediatric patients, the rate should not exceed 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower). For maintenance doses in pediatric patients, the rate should not exceed 1 to 2 mg PE/kg/min (or 100 mg PE/min, whichever is slower). 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).
• After the initial maintenance dose, subsequent maintenance doses should be individualized by monitoring serum phenytoin concentrations to achieve a target therapeutic concentration of phenytoin [see Dosage and Administration (2.5) and Warnings and Precautions (5.17)].

Adult and Pediatric Non-emergent Loading and Maintenance Dosing:

Table 2. Non-emergent Loading Dosages

Population	Dosage	Infusion rate
Adult	10 mg PE/kg to 20 mg PE/kg	Not to exceed a maximum rate of 150 mg PE/min
Pediatric (Birth to less than 17 years of age)	10 mg PE/kg to 15 mg PE/kg	1 mg PE/kg/min to 2 mg PE/kg/min, or 150 mg PE/min, whichever is slower

Table 3. Maintenance Dosages

Population	Dosage	Infusion rate
Adult	Initial Maintenance Dosage: 4 mg PE/kg/day to 6 mg PE/kg/day in divided doses	Not to exceed a maximum rate of 150 mg PE/min
Pediatric (Birth to less than 17 years of age)	Initial Maintenance Dosage: 2 mg PE/kg to 4 mg PE/kg (dose given 12 hours after the loading dose)	1 mg PE/kg/min to 2 mg PE/kg/min, or 100 mg PE/min, whichever is slower
	Maintenance Dosage after Initial Maintenance Dosage: 4 mg PE/kg/day to 8 mg PE/kg/day in divided doses (continued every 12 hours after initial maintenance dose)	1 mg PE/kg/min to 2 mg PE/kg/min, or 100 mg PE/min, whichever is slower

Because of the risks of cardiac and local toxicity associated with intravenous CEREBYX, oral phenytoin should be used whenever possible. Intramuscular administration of CEREBYX should ordinarily not be used in pediatric patients.