What is the treatment for a patient experiencing seizures due to non-adherence to their Keppra (levetiracetam) regimen?

Treatment of Seizures Due to Keppra Non-Adherence

For a patient actively seizing due to Keppra non-adherence, administer a levetiracetam loading dose of 30-60 mg/kg IV (maximum 4500 mg) at a rate of 100 mg/min after initial benzodiazepine treatment. 1

Immediate Management Algorithm

Step 1: Initial Seizure Control

• Administer benzodiazepines first if the patient is actively seizing (lorazepam 0.1 mg/kg IV, maximum 2 mg per dose, may repeat once). 2
• Assess airway, breathing, and circulation; provide supplemental oxygen and check blood glucose. 2

Step 2: Levetiracetam Loading Dose

For adults:

• Loading dose: 30-60 mg/kg IV (maximum 4500 mg) administered at 100 mg/min. 1
• Typical fixed dosing in adults is 1500-3000 mg IV for most patients. 1
• No cardiac monitoring is required during levetiracetam administration, unlike phenytoin/fosphenytoin. 1

For pediatric patients:

• Loading dose: 40 mg/kg IV (maximum 2500 mg) bolus for both convulsive and non-convulsive status epilepticus. 2

Step 3: Maintenance Dosing

After seizure control:

• Resume maintenance levetiracetam at the patient's previous home dose, or initiate standard dosing if previously inadequate. 2
• Standard maintenance: 500-1500 mg IV/PO every 12 hours in adults. 3
• Pediatric maintenance: 15-30 mg/kg IV every 12 hours (maximum 1500 mg per dose). 2

Key Clinical Considerations

Route of Administration

• Either oral or parenteral routes are acceptable for non-actively seizing patients resuming therapy, as there is no evidence supporting one route over the other for preventing early recurrent seizures. 2
• The choice of administration route is at the discretion of the emergency physician. 2

If Seizures Persist After Levetiracetam

Levetiracetam is a Level C recommendation as a second-line agent after benzodiazepines for refractory status epilepticus. 2

If seizures continue despite adequate benzodiazepine and levetiracetam loading:

• Consider IV phenytoin/fosphenytoin (18-20 mg/kg) or valproate (20-30 mg/kg at 40 mg/min) as alternative second-line agents. 2
• Valproate may be preferred over phenytoin due to faster administration and fewer adverse effects. 2
• For truly refractory cases, consider propofol or barbiturates with ICU-level care. 2

Important Caveats and Pitfalls

Dosing Concerns

• Recent evidence suggests loading doses >40 mg/kg may increase intubation rates (45.8% vs 26.8-28.2% with lower doses) without improving seizure termination. 4
• However, guideline recommendations still support up to 60 mg/kg for status epilepticus based on expert consensus. 1
• Consider using 30-40 mg/kg as a reasonable middle ground to balance efficacy and safety. 1, 4

Adverse Effects to Monitor

• Somnolence and respiratory depression can occur, particularly with higher doses or in overdose situations. 3, 5
• Unlike phenytoin, levetiracetam does not cause hypotension or cardiac dysrhythmias. 2, 1
• Minimal drug interactions make it suitable for patients on multiple medications. 1

Withdrawal Considerations

• Avoid abrupt discontinuation of levetiracetam to reduce risk of increased seizure frequency and status epilepticus. 3
• Address medication adherence barriers before discharge to prevent recurrence. 3

Renal Dosing

• Levetiracetam is primarily renally cleared; dose adjustments are necessary in renal impairment. 3, 6
• For patients on dialysis or CVVH, consider 1000 mg every 12 hours with therapeutic drug monitoring. 6