Aurantin Dosage/Direction for Use

The dose, concentration in dosing solutions, and infusion rate of intravenous (IV) fosphenytoin sodium (Aurantin) 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. Fosphenytoin should always be prescribed and dispensed in phenytoin sodium equivalent units (PE). Fosphenytoin sodium (Aurantin) has important differences in administration from those for parenteral phenytoin sodium (see Special Precautions for Disposal and Other Handling under Cautions for Usage).
Adult Dosing: Status Epilepticus: The loading dose of fosphenytoin sodium (Aurantin) is 15 to 20 mg PE/kg administered at 100 to 150 mg PE/min.
The rate of intravenous fosphenytoin sodium (Aurantin) administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute because of the risk of severe hypotension. 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 (Aurantin) 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 IV benzodiazepine, will usually be necessary for the control of status epilepticus.
The loading dose should be followed by maintenance doses of either parenteral fosphenytoin or oral/parenteral phenytoin.
Intramuscular (IM) fosphenytoin sodium (Aurantin) 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 fosphenytoin sodium (Aurantin) have been given by the IM route for other indications.
The typical fosphenytoin sodium (Aurantin) infusion administered to a 50 kg patient would take between 5 and 7 minutes. Note that the delivery of an identical molar dose of phenytoin using parenteral phenytoin or generic phenytoin sodium injection cannot be accomplished in less than 15 to 20 minutes because of the untoward cardiovascular effects that accompany the direct IV administration of phenytoin at rates greater than 50 mg/min.
If rapid phenytoin loading is a primary goal, IV administration of fosphenytoin sodium (Aurantin) is preferred because the time to achieve therapeutic plasma phenytoin concentrations is greater following IM administration than that following IV administration.
If administration of fosphenytoin sodium (Aurantin) does not terminate seizures, the use of other anticonvulsants and other appropriate measures should be considered.
Non-emergent Loading and Maintenance Dosing: The loading dose of fosphenytoin sodium (Aurantin) is 10 to 20 mg PE/kg given IV or IM. The rate of administration for IV fosphenytoin sodium (Aurantin) 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 fosphenytoin sodium (Aurantin) infusions.
Following either the loading dose for Status Epilepticus or a Non-Emergent situation, the initial daily maintenance dose of fosphenytoin sodium (Aurantin) is 4 to 6 mg PE/kg/day. After administration of a loading dose, maintenance doses should typically be started at the next identified dosing interval. For example, if the intended dose frequency is every 12 hours then the first maintenance dose of fosphenytoin sodium (Aurantin) should be administered 12 hours after the loading dose.
Maintenance doses should be individualized by monitoring trough plasma phenytoin concentrations to achieve a target therapeutic concentration of phenytoin. Phenytoin equivalent doses are usually selected to attain therapeutic plasma total phenytoin trough concentrations of 10 to 20 mcg/mL, (unbound phenytoin trough concentrations of 1 to 2 mcg/mL).
IM or IV Substitution for Oral Phenytoin Therapy: Parenteral fosphenytoin can be substituted for oral phenytoin sodium therapy at the same total daily phenytoin sodium equivalents (PE) dose
Phenytoin capsules are approximately 90% bioavailable by the oral route. Phenytoin, supplied as fosphenytoin, is 100% bioavailable by both the IM and IV routes. For this reason, plasma phenytoin concentrations may increase modestly when IM or IV fosphenytoin is substituted for oral phenytoin sodium therapy.
The rate of administration for IV fosphenytoin sodium (Aurantin) should be no greater than 150 mg PE/min.
In controlled trials, IM fosphenytoin sodium (Aurantin) was administered as a single daily dose utilizing either one or two injection sites. Some patients may require more frequent dosing.
Dosing in Special Populations: Patients with Renal or Hepatic Disease: See General under Precautions.
Elderly Patients: Phenytoin clearance is decreased slightly in elderly patients and lower or less frequent dosing may be required (see Pharmacology: Pharmacokinetics: Special Populations: Age under Actions).
Pediatric Patients: Fosphenytoin sodium (Aurantin) may be administered by IV infusion to pediatric patients of all ages. The doses of fosphenytoin sodium (Aurantin) for pediatric patients have been predicted from the known pharmacokinetics of fosphenytoin sodium (Aurantin) and of parenteral phenytoin in adults and pediatric patients (see Pharmacology: Pharmacokinetics: Special Populations: Pediatrics under Actions).
Status Epilepticus: The loading dose of fosphenytoin sodium (Aurantin) is 15 mg PE/kg. The recommended infusion rate is 2 mg PE/kg/min. Due to the risk of hypotension, fosphenytoin sodium (Aurantin) 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 sodium (Aurantin) infusions.
Intramuscular (IM) fosphenytoin sodium (Aurantin) 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 fosphenytoin sodium (Aurantin) have been given by the IM route.
Non-emergent Loading and Maintenance Dosing: The loading dose of fosphenytoin sodium (Aurantin) is 10 to 15 mg PE/kg. The recommended infusion rate is 1 to 2 mg PE/kg/min. Due to the risk of hypotension, fosphenytoin sodium (Aurantin) 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 sodium (Aurantin) infusions.
Following either the loading dose for Status Epilepticus or a Non Emergent situation, the initial maintenance dose of fosphenytoin sodium (Aurantin) is 2 to 4 mg PE/kg which should be given 12 hours after the loading dose and then continued every 12 hours (4 to 8 mg PE/kg/day) at a rate of 1 to 2 mg PE/kg/min (no faster than 100 mg PE/min).
Maintenance doses should be individualized by monitoring trough plasma phenytoin concentrations to achieve a target therapeutic concentration of phenytoin. Phenytoin doses are usually selected to attain therapeutic plasma total phenytoin trough concentrations of 10 to 20 mcg/mL, (unbound phenytoin trough concentrations of 1 to 2 mcg/mL).
Laboratory Tests: Phenytoin equivalent doses are usually selected to attain therapeutic plasma total phenytoin concentrations of 10 mcg/mL to 20 mcg/mL (unbound phenytoin concentrations of 1 mcg/mL to 2 mcg/mL). Prior to complete conversion, immunoanalytical techniques may significantly overestimate plasma phenytoin concentrations due to cross-reactivity with fosphenytoin. Chromatographic assay methods (e.g., high performance liquid chromatography [HPLC]) accurately quantitate phenytoin concentrations in biological fluids in the presence of fosphenytoin. Blood samples should be collected in tubes containing ethylenediaminetetraacetic acid (EDTA), not heparin. However, even with specific assay methods, phenytoin concentrations measured before conversion of fosphenytoin is complete will not reflect phenytoin concentrations ultimately achieved.
Therefore, following fosphenytoin sodium (Aurantin) administration, it is recommended that phenytoin concentrations not be monitored until conversion to phenytoin is essentially complete. This occurs within approximately 2 hours after the end of IV infusion and 4 hours after IM injection.