What is the recommended dose of IV (intravenous) fosphenytoin (phenytoin) in an Intensive Care Unit (ICU) setting?

IV Fosphenytoin Dosing in the ICU

For ICU patients requiring IV fosphenytoin, administer a loading dose of 18-20 mg PE/kg at a maximum infusion rate of 150 mg PE/min in adults (or 2 mg PE/kg/min in pediatric patients, whichever is slower), followed by maintenance dosing of 4-6 mg PE/kg/day in divided doses. 1, 2

Loading Dose Administration

Adults:

• Loading dose: 18-20 mg PE/kg IV 1, 2
• Maximum infusion rate: 150 mg PE/min 1, 2
• For status epilepticus specifically, use 15-20 mg PE/kg at 100-150 mg PE/min 2

Pediatric Patients:

• Loading dose: 15-20 mg PE/kg IV 2
• Maximum infusion rate: 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) 1, 2

Maintenance Dosing

• Adults: 4-6 mg PE/kg/day in divided doses 2
• Pediatric: 2-4 mg PE/kg every 12 hours at 1-2 mg PE/kg/min (or 100 mg PE/min, whichever is slower) 2

Critical Safety Monitoring Requirements

Mandatory continuous monitoring during and after infusion: 1, 2

• Cardiac monitoring for bradycardia, arrhythmias, and heart block 1, 3
• Blood pressure monitoring for hypotension 1, 3
• Reduce infusion rate immediately if heart rate decreases by 10 beats/min 1, 3

The FDA boxed warning emphasizes that exceeding the maximum infusion rate carries significant risk of severe hypotension and cardiac arrhythmias, potentially leading to cardiac arrest 2. Research confirms that rapid loading at 150 mg PE/min is generally well-tolerated but can cause transient hypotension in some patients 4.

Preparation and Administration

Solution preparation: 1, 3

• Dilute only in normal saline to a final concentration ≥5 mg PE/mL 1, 3
• Never mix with dextrose-containing solutions—causes precipitation 1, 3

Dosing notation: 3

• Always express dose in "mg PE" (phenytoin equivalents) to prevent 10-fold dosing errors 3
• Ensure the appropriate volume is withdrawn from the vial (50 mg PE/mL concentration) 2

Pharmacokinetic Advantages in ICU Setting

Fosphenytoin offers several practical advantages over phenytoin in the ICU: 5, 6

• Conversion half-life of 7-15 minutes achieves therapeutic phenytoin levels rapidly 5
• Therapeutic unbound phenytoin concentrations (1-2 mg/L) achieved within 10-30 minutes 5, 4
• Significantly fewer local tissue reactions and extravasation injuries 1, 6
• Can be administered intramuscularly if IV access is problematic (though not preferred in emergencies) 2, 5

Research in SAH patients demonstrated that all patients achieved therapeutic free phenytoin levels at the end of infusion, though most experienced transient supratherapeutic levels (mean 17.7 mg/L) that normalized by 24 hours 4.

Special Population Adjustments

Patients with decreased protein binding (renal/hepatic disease, hypoalbuminemia, elderly): 5

• Reduce infusion rate by 25-50% 5
• Higher unbound phenytoin concentrations occur earlier, increasing risk of systemic adverse effects 5

Neonates: 3

• Phenobarbital is preferred over fosphenytoin due to increased toxicity risk from decreased protein binding 3

Common Adverse Effects

Cardiovascular (most serious): 1, 2

• Hypotension, bradycardia, cardiac arrhythmias 1, 2
• Risk increases with rapid infusion rates 2, 4

Infusion-related (generally mild): 1, 2

• Transient paresthesias and pruritus (occur with rapid infusion but are not dangerous) 1
• Pruritus, dizziness, somnolence, ataxia, nystagmus 2

Critical Pitfalls to Avoid

• Never infuse faster than maximum recommended rates—causes hypotension, bradyarrhythmias, and cardiac arrest 7, 2
• Never use glucose-containing solutions—causes drug precipitation 1, 3
• Do not confuse mg PE with vial concentration (50 mg PE/mL)—leads to dosing errors 3, 2
• When combining with benzodiazepines, prepare for potential respiratory depression 3
• Avoid abrupt discontinuation—may precipitate status epilepticus 7