The dose, concentration, and infusion rate of intravenous fosphenytoin 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 should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). 1.5 mg of fosphenytoin sodium is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg PE. The amount and concentration of fosphenytoin is always expressed in terms of mg of phenytoin sodium equivalents (mg PE). 

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

Caution must be used when administering fosphenytoin due to the risk of dosing errors (see WARNINGS). Medication errors associated with fosphenytoin have resulted in patients receiving the wrong dose of fosphenytoin. Fosphenytoin is marketed in 2 mL vials containing a total of 100 mg PE and 10 mL vials containing a total of 500 mg PE. Both vials contain a concentration of 50 mg PE/mL. Errors 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 since each of the vials actually contains a total of 100 mg PE or 500 mg PE. In some cases, ten-fold overdoses were associated with fatal outcomes. To help minimize confusion, the prescribed dose of fosphenytoin should always be expressed in milligrams of phenytoin equivalents (mg PE). Additionally, when ordering and storing fosphenytoin, consider displaying the total drug content (i.e., 100 mg PE/ 2 mL or 500 mg PE/ 10 mL) instead of concentration in computer systems, pre-printed orders, and automated dispensing cabinet databases to help ensure that total drug content can be clearly identified. Care should be taken to ensure the appropriate volume of fosphenytoin is withdrawn from the vial when preparing the dose for administration. Attention to these details may prevent some fosphenytoin medication errors from occurring.

Prior to intravenous infusion, dilute fosphenytoin 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 in any solution should be 25 mg PE/mL. When fosphenytoin is given as an intravenous infusion, fosphenytoin 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 or discoloration prior to administration, whenever solution and container permit. 

Status Epilepticus

  * The loading dose of fosphenytoin 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 fosphenytoin infusions.
  * Because the full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate, other measures, including concomitant administration of an intravenous benzodiazepine, will usually be necessary for the control of status epilepticus.
  * The loading dose should be followed by maintenance doses of either fosphenytoin or phenytoin.



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

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

Nonemergent Loading and Maintenance Dosing

Because of the risks of cardiac and local toxicity associated with intravenous fosphenytoin, oral phenytoin should be used whenever possible. 

The loading dose of fosphenytoin is 10 to 20 mg PE/kg given intravenous or intramuscular. The rate of administration for intravenous fosphenytoin 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 20 minutes after the end of fosphenytoin infusion).

The initial daily maintenance dose of fosphenytoin is 4 to 6 mg PE/kg/day in divided doses.

Intramuscular or Intravenous Substitution for Oral Phenytoin Therapy

When treatment with oral phenytoin is not possible, fosphenytoin can be substituted for oral phenytoin at the same total daily dose.

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

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

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