Fosphenytoin

Dosing in Patients with Renal or Hepatic Impairment or Hypoalbuminemia Because the fraction of unbound phenytoin (the active metabolite of fosphenytoin sodium injection) is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients.

After IV fosphenytoin sodium injection 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 Warnings and Precautions ].

Renal and/or Hepatic Impairment, or Hypoalbuminemia The liver is the site of biotransformation. Patients with impaired liver function, elderly patients, or those who are gravely ill may show early toxicity. Because the fraction of unbound phenytoin (the active metabolite of fosphenytoin sodium) is increased in patients with renal or hepatic disease, or in those with hypoalbuminemia, the monitoring of phenytoin serum levels should be based on the unbound fraction in those patients.

After IV 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.

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 ]. 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.

Preparation Prior to intravenous (IV) infusion, dilute fosphenytoin sodium injection 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 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.

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] . 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 ] .

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 [See table below.] 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.