Adding Phenytoin to Levetiracetam for Breakthrough Seizures
For a patient on Keppra (levetiracetam) experiencing breakthrough seizures, add phenytoin at a loading dose of 20 mg/kg divided in maximum doses of 400 mg every 2 hours orally, or 18 mg/kg IV at maximum rate of 50 mg/min. 1
Dosing Considerations for Phenytoin
- The recommended loading dose of phenytoin is 20 mg/kg for oral administration or 18 mg/kg for IV administration 1
- For IV administration, phenytoin should be infused at a maximum rate of 50 mg/min to minimize risk of cardiovascular adverse effects 1
- For oral administration, divide doses in maximum increments of 400 mg every 2 hours 1
- After loading, maintenance dosing should be individualized to achieve therapeutic serum levels of 10-20 mcg/mL 2
- Monitor for adverse effects including hypotension, cardiac dysrhythmias, and extravasation injuries with IV administration 1
Route Selection Considerations
- IV administration achieves therapeutic levels more quickly but carries higher risk of adverse effects including hypotension, bradyarrhythmias, and cardiac arrest 1
- Oral administration is cheaper but takes >5 hours to reach therapeutic levels 1
- If using IV route, continuous cardiac and blood pressure monitoring is required 1
- Fosphenytoin (18 PE/kg IV) may be considered as an alternative to IV phenytoin with fewer adverse events in head-to-head analysis 1
Monitoring Requirements
- Serum phenytoin levels should be monitored to ensure therapeutic range (10-20 mcg/mL) 2
- Monitor for cardiovascular adverse effects during IV administration, including continuous ECG and blood pressure monitoring 1
- If 50% QRS widening or hypotension occurs during administration, hold the remainder of the dose 1
- Allow 7-10 days to achieve steady-state blood levels with phenytoin before making further dosage adjustments 2
Alternative Considerations
- Valproate (30 mg/kg IV at rate of 10 mg/kg/min) may be considered as an alternative with potentially fewer cardiovascular side effects 1, 3
- Levetiracetam dose adjustment could be considered before adding phenytoin - doses up to 3000 mg/day have been studied and shown efficacy in refractory epilepsy 4, 5, 6
- Some patients may respond to levetiracetam doses up to 4000 mg/day, though adverse effects like somnolence and asthenia increase at higher doses 6
Common Pitfalls and Caveats
- Phenytoin has only shown 56% success in terminating status epilepticus when used after benzodiazepines 1, 3
- Phenytoin requires a filter and infusion pump for IV administration 1
- Phenytoin is incompatible with glucose-containing solutions 1
- Extravasation of IV phenytoin can cause severe tissue damage (purple glove syndrome) 1
- When switching between different phenytoin formulations, careful monitoring of serum levels is required due to differences in bioavailability 2