FOSPHENYTOIN SODIUM

FOSPHENYTOIN SODIUM — fosphenytoin sodium injection
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WARNING: CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION RATES

The rate of intravenous fosphenytoin sodium injection administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute in adults and 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after administering intravenous fosphenytoin sodium injection. Although the risk of cardiovascular toxicity increases with infusion rates above the recommended infusion rate, these events have also been reported at or below the recommended infusion rate. Reduction in rate of administration or discontinuation of dosing may be needed [see Dosage and Administration (2.3, 2.4) and Warnings and Precautions (5.2)].

1 INDICATIONS AND USAGE

Fosphenytoin sodium injection, USP is indicated for the treatment of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. Fosphenytoin sodium injection, USP can also be substituted, short-term, for oral phenytoin. Fosphenytoin sodium injection, USP 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 fosphenytoin sodium injection because of the risk of dosing errors [see Warnings and Precautions (5.1)].

Phenytoin Sodium Equivalents (PE)

The dose, concentration, and infusion rate of fosphenytoin sodium injection 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. Fosphenytoin sodium injection 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 fosphenytoin sodium injection 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 fosphenytoin sodium injection 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 fosphenytoin sodium injection is withdrawn from the vial when preparing the dose for administration. Attention to these details may prevent some fosphenytoin sodium injection medication errors from occurring.

2.2 Preparation

Prior to intravenous (IV) infusion, dilute fosphenytoin sodium injection in 5% dextrose or 0.9% saline solution for injection to a concentration ranging from 1.5 to 25 mg PE/mL. The maximum concentration of fosphenytoin sodium injection in any solution should be 25 mg PE/mL. When fosphenytoin sodium injection is given as an IV infusion, fosphenytoin sodium injection 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 fosphenytoin sodium injection 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 fosphenytoin sodium injection infusions.
  • Because the full antiepileptic effect of phenytoin, whether given as fosphenytoin sodium injection 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 fosphenytoin sodium injection or phenytoin [see Dosage and Administration (2.4)].
  • If administration of fosphenytoin sodium injection 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 fosphenytoin sodium injection have been given by the IM route for other indications when IV access is impossible, IM fosphenytoin sodium injection 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 fosphenytoin sodium injection should ordinarily not be used in pediatric patients. When IV access has been impossible, loading doses of fosphenytoin sodium injection 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 fosphenytoin sodium injection 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 fosphenytoin sodium injection 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 fosphenytoin sodium injection, oral phenytoin should be used whenever possible. Intramuscular administration of fosphenytoin sodium injection should ordinarily not be used in pediatric patients.

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