What are the loading and maintenance dosages for antiepileptic drugs (AEDs) in seizure management?

Seizure Loading and Maintenance Dosages

For acute seizure management in the emergency department, phenytoin should be loaded at 18 mg/kg IV at a maximum rate of 50 mg/min, or fosphenytoin at 18 PE/kg IV at a maximum rate of 150 PE/min, with fosphenytoin preferred due to fewer adverse events. 1

Loading Dose Strategies by Medication

First-Line Agents for Status Epilepticus

Phenytoin:

• IV loading: 18-20 mg/kg at maximum rate of 50 mg/min 1, 2
• Oral loading: 20 mg/kg divided in maximum doses of 400 mg every 2 hours 1, 2
• Achieves therapeutic levels (>10 μg/mL) in 97% of patients immediately after IV infusion 1, 3
• Oral route takes >5 hours to reach therapeutic levels 1, 2
• Critical caveat: IV administration carries serious risks including hypotension, bradyarrhythmias, cardiac arrest, and extravasation injuries 1, 2, 3

Fosphenytoin (Preferred over IV phenytoin):

• IV loading: 18 PE/kg at maximum rate of 150 PE/min 1, 2
• Can also be given IM 1
• Fewer adverse events in head-to-head comparison with IV phenytoin 1, 2, 3
• Faster administration rate (150 PE/min vs 50 mg/min for phenytoin) 3

Alternative Loading Agents

Levetiracetam:

• Oral loading: 1,500 mg as single dose 1, 2
• IV loading: Safe and well tolerated up to 60 mg/kg 1, 2
• No seizures within 24 hours of loading in oral loading studies 1
• Minimal adverse effects (fatigue, dizziness, rarely infusion site pain) 1

Valproate:

• IV loading: Up to 30 mg/kg at maximum rate of 10 mg/kg/min 1, 2
• Only transient local irritation at injection site 1

Carbamazepine:

• Oral loading: 8 mg/kg oral suspension as single load 1, 2
• No IV formulation available 1
• Oral tablet has slow/erratic absorption 1

Lamotrigine:

• Oral loading: 6.5 mg/kg single dose 1, 2
• Critical restriction: Only if patient was on lamotrigine for >6 months without history of rash and off lamotrigine for <5 days 1, 2
• Never load if: History of rash or patient not previously on lamotrigine due to risk of serious rashes 1

Gabapentin:

• Oral loading: 900 mg/day (300 mg three times daily) for 3 days 1, 2
• No IV formulation available 1
• No difference in seizure recurrence compared to slower loading 1

Maintenance Dosing After Loading

Phenytoin Maintenance

• Standard maintenance: 200-700 mg/day orally 3
• Initiate 24 hours after loading dose 4
• Takes 6-9 days to reach stable therapeutic levels without loading 3
• Divided daily dosing: One 100-mg capsule three times daily, adjusted to suit requirements 4
• Once-daily dosing: 300 mg daily may be considered once seizure control is established with divided doses 4
• Pediatric maintenance: 4-8 mg/kg/day (maximum 300 mg/day) 4

General Maintenance Principles

• Target therapeutic serum phenytoin levels of 10-20 mcg/mL 4
• Allow 7-10 days to achieve steady-state blood levels before adjusting dosage 4
• Frequent serum level monitoring required when switching formulations or brands 4

Clinical Decision-Making Algorithm

When to Load in the Emergency Department

High-risk patients requiring loading doses: 2

• Refractory status epilepticus after benzodiazepine failure 2
• Known seizure disorder with missed doses or subtherapeutic levels 2
• Age ≥40 years 1, 2
• Alcoholism (especially with seizure history - 25.2% early recurrence rate) 1, 2
• Hyperglycemia 1, 2
• Glasgow Coma Scale score <15 1, 2

Timing consideration: Mean time to first early seizure recurrence is 121 minutes, with >85% occurring within 360 minutes 2

Route Selection Algorithm

Choose IV fosphenytoin when: 1, 2, 3

• Rapid therapeutic levels needed (achieves levels within minutes)
• Patient can tolerate IV access
• Resources available for cardiac monitoring

Choose oral phenytoin when: 1, 2

• Patient stable and can tolerate oral intake
• Time to therapeutic level (>5 hours) is acceptable
• Cost is a concern (oral is cheaper)
• Avoiding IV complications is priority

Choose levetiracetam when: 1, 2

• Phenytoin contraindicated or not tolerated
• Simpler safety profile desired
• Patient has cardiac risk factors

Critical Pitfalls to Avoid

Phenytoin-specific hazards: 1, 2, 3

• Never exceed 50 mg/min IV infusion rate (risk of cardiac arrest)
• Requires cardiac monitoring during IV administration
• Requires filter and infusion pump for IV administration 1
• High risk of extravasation injuries with IV phenytoin 1

Lamotrigine loading contraindications: 1, 2

• Never load patients not previously on lamotrigine
• Never load if any history of rash
• Never load if off lamotrigine >5 days

Monitoring requirements: 1

• Most loading studies used serum drug levels as surrogate outcome rather than direct seizure prevention measurement
• Therapeutic drug monitoring essential for phenytoin due to nonlinear pharmacokinetics 5

Patient-specific considerations: 4

• Patients with renal or liver disease should not receive oral loading regimen
• Oral loading should only be done in clinic or hospital setting with close serum level monitoring