What to do for subtherapeutic Dilantin (phenytoin) levels?

Management of Subtherapeutic Phenytoin Level (4.7 mcg/mL)

For a phenytoin level of 4.7 mcg/mL, you should administer a loading dose of 15-20 mg/kg to rapidly achieve therapeutic levels, with the route (IV versus oral) determined by whether the patient is having breakthrough seizures or requires immediate seizure control. 1, 2

Immediate Assessment

First, determine if the patient is experiencing breakthrough seizures or is at imminent risk:

• If breakthrough seizures are occurring: Administer 15-20 mg/kg IV at a maximum rate of 50 mg/min, requiring continuous cardiac monitoring for bradycardia, arrhythmias, heart block, and hypotension throughout the infusion 1, 2
• If no active seizures but subtherapeutic level: Either IV or oral loading is acceptable, with the choice based on urgency, cost considerations, and patient factors 1

Loading Dose Protocols

Intravenous Route

• Standard IV loading dose: 15-20 mg/kg infused over 10-20 minutes, with infusion rate not exceeding 50 mg/min in adults 2
• Maximum initial dose: 1000 mg 2
• Mandatory cardiac monitoring during administration due to significant risk of hypotension, bradycardia, and arrhythmias 2
• Reduce infusion rate by 50% if heart rate decreases by 10 beats per minute 2
• Dilute only in normal saline—phenytoin precipitates in glucose-containing solutions 2
• IV route achieves therapeutic levels faster but carries more serious adverse effects including hypotension, bradyarrhythmias, cardiac arrest, and extravasation injuries 1

Oral Route

• Oral loading dose: 18-20 mg/kg divided into maximum doses of 400 mg every 2 hours 1, 2, 3
• Example regimen: 1000 mg divided as 400 mg, 300 mg, and 300 mg given at 2-hour intervals 2
• Time to therapeutic levels: Takes more than 5 hours, with approximately 48-55% of patients achieving therapeutic levels within 3-10 hours 2
• Advantages: Significantly cheaper than IV and safer (no cardiac complications), with no significant difference in seizure recurrence between oral and IV loading 1
• Disadvantage: Unsuitable for acute seizure control due to delayed onset 2

Alternative: Fosphenytoin

Consider IV fosphenytoin (18 PE/kg at maximum 150 PE/min) as it has fewer adverse events than phenytoin in head-to-head comparison and is now available as generic with significant cost reduction 1, 2

Maintenance Dosing

• Begin maintenance therapy at 4-7 mg/kg/day (typically 300-400 mg/day in adults) starting 6-12 hours after the loading dose 1, 2, 3
• Allow 7-10 days to achieve steady-state blood levels before making further dosage adjustments 3

Critical Pitfalls to Avoid

• Never load phenytoin orally in patients requiring immediate seizure control—IV route is essential for status epilepticus 2
• Never exceed 50 mg/min infusion rate in adults to minimize cardiac complications 2
• Do not use glucose-containing solutions for IV phenytoin as it will precipitate 2
• Monitor serum levels closely when switching between formulations, as there is approximately an 8% increase in drug content with the free acid form over the sodium salt 3

Expected Efficacy

• IV phenytoin at 15-18 mg/kg controls seizures in 80% of patients with repetitive seizures, though efficacy drops below 40% when anoxic or metabolic disturbances are present 2
• A loading dose of 18 mg/kg achieves therapeutic levels (>10 mg/L) at 24 hours post-infusion in nearly all patients 2