IV Fosphenytoin Dosing
The recommended IV fosphenytoin loading dose is 15-20 mg PE/kg for both adults and pediatric patients, with critical differences in maximum infusion rates: adults should receive no faster than 100-150 mg PE/min, while pediatric patients must not exceed 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower). 1
Loading Dose for Status Epilepticus
- Adults: Administer 15-20 mg PE/kg IV at a rate of 100-150 mg PE/min 1
- Pediatric patients: Administer 15-20 mg PE/kg IV at a rate of 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) 1
The FDA explicitly warns that exceeding these infusion rates increases risk of severe hypotension and cardiac arrhythmias, requiring careful cardiac monitoring during and after administration 1.
Non-Emergent Loading and Maintenance Dosing
- Adults: Loading dose of 10-20 mg PE/kg IV, followed by initial maintenance of 4-6 mg PE/kg/day in divided doses 1
- Pediatric patients: Loading dose of 10-15 mg PE/kg at 1-2 mg PE/kg/min (or 150 mg PE/min, whichever is slower), with initial maintenance of 2-4 mg PE/kg every 12 hours at 1-2 mg PE/kg/min (or 100 mg PE/min, whichever is slower) 1
Critical Preparation Requirements
- Dilute only in normal saline to achieve a final concentration ≥5 mg PE/mL 2
- Never use dextrose-containing solutions as this causes drug precipitation 2, 1
- All prescriptions must specify "mg PE" (phenytoin equivalents) rather than "mg" to prevent potentially fatal 10-fold dosing errors 2
Mandatory Monitoring During Infusion
- Reduce infusion rate immediately if heart rate decreases by 10 beats/min 2
- Monitor continuously for bradycardia, arrhythmias, heart block, and hypotension 2
- Have resuscitation equipment and respiratory support immediately available, especially if benzodiazepines were administered first 2
Special Population Considerations
Neonates and Young Infants
- Phenobarbital is strongly preferred over fosphenytoin/phenytoin in neonates due to significantly increased toxicity risk from decreased protein binding, which leads to dangerously elevated free phenytoin levels 2, 3
Patients with Renal or Hepatic Disease
- Reduce infusion rate by 25-50% in patients with decreased protein binding capacity (renal disease, hepatic disease, hypoalbuminemia, elderly) to avoid earlier and higher unbound phenytoin concentrations 4
- Use with extreme caution in end-stage renal disease patients due to risk of acute hyperphosphatemia from phosphate metabolites 5
Common Dosing Errors to Avoid
- Confusing "mg PE" with actual drug concentration in the vial - always verify the appropriate volume is withdrawn when preparing for administration 1
- Infusing too rapidly, which dramatically increases hypotension and arrhythmia risk 2
- Mixing with glucose-containing solutions, causing precipitation 2
- Failing to prepare for respiratory depression when combining with benzodiazepines 2
Pharmacokinetic Considerations
- Fosphenytoin converts to phenytoin with a half-life of 7-15 minutes via blood and tissue phosphatases 4
- Bioavailability of derived phenytoin is approximately 100% following IV administration 4
- Rapid IV infusion rates (100-150 mg PE/min) compensate for conversion-related delays, achieving therapeutic unbound phenytoin concentrations comparable to direct phenytoin administration 4