Fosphenytoin Dosing in the ICU
Loading Dose Recommendation
For ICU patients requiring fosphenytoin, administer a loading dose of 18-20 mg PE/kg (phenytoin equivalents per kilogram) intravenously. 1, 2, 3
Administration Rate and Safety Parameters
Infusion Rate
- Maximum infusion rate: 150 mg PE/min in adults 1, 3
- Pediatric patients: 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) 4, 3
- This faster rate compared to phenytoin (50 mg/min) is a key advantage of fosphenytoin, with fewer adverse cardiovascular events 1, 5
Mandatory Monitoring During Infusion
- Continuous cardiac monitoring is required - watch for bradycardia, arrhythmias, and heart block 4, 6
- Blood pressure monitoring - hypotension can occur, particularly with rapid infusion 4, 3
- Reduce infusion rate if heart rate decreases by 10 beats/min 4, 6
Preparation and Administration Details
Solution Preparation
- Dilute only in normal saline to a final concentration ≥5 mg PE/mL 4, 6
- Never mix with dextrose-containing solutions - this causes drug precipitation 4, 6
Dosing Specifications
- Always express dose in PE (phenytoin equivalents) to prevent 10-fold dosing errors 6, 3
- For status epilepticus refractory to benzodiazepines: 15-20 mg PE/kg loading dose 1, 2
- For non-emergent situations: 10-20 mg PE/kg loading dose 2, 3
Expected Pharmacokinetic Profile
Time to Therapeutic Levels
- Therapeutic free phenytoin levels (>1 mcg/mL) achieved within 10 minutes of IV infusion completion 5, 7
- Conversion half-life from fosphenytoin to phenytoin: 7-15 minutes 5
- 97% of patients achieve therapeutic levels (>10 mg/L) immediately after infusion 1
Important Pharmacokinetic Consideration
- Most patients (93%) experience transient supratherapeutic free phenytoin levels at end of infusion (mean 17.7 mg/L), which normalize by 20 minutes post-infusion 7
- This overshoot is generally well-tolerated but warrants close cardiovascular monitoring 7
Special Population Adjustments
Patients with Decreased Protein Binding
- Reduce infusion rate by 25-50% in patients with:
- These patients achieve higher unbound phenytoin concentrations and increased risk of systemic adverse effects 5
Neonates
- Phenobarbital is preferred over fosphenytoin in neonates due to increased toxicity risk from decreased protein binding 6
Common Pitfalls to Avoid
Critical Errors
- Confusing total drug amount with concentration - ensure appropriate volume is withdrawn from vial (50 mg PE/mL concentration) 2, 3
- Infusing too rapidly - increases risk of severe hypotension and cardiac arrhythmias 6, 3
- Using glucose-containing IV solutions - causes immediate drug precipitation 4, 6
Adverse Effects Profile
- Transient paresthesias and pruritus occur with rapid infusion rates but are generally mild 1, 5
- Cardiovascular complications (hypotension, bradycardia, arrhythmias) are the most serious concerns 1, 2, 3
- Fosphenytoin has significantly fewer local tissue reactions and extravasation injuries compared to phenytoin 1, 8