What to add to Levetiracetam 500 mg Q12 for ongoing seizures?

Adding a Second Antiepileptic Medication to Levetiracetam for Ongoing Seizures

For patients already on levetiracetam 500 mg Q12 who continue to experience brief seizure episodes, either valproate or fosphenytoin should be added as a second-line agent, as both have similar efficacy for seizure control. 1

Assessment of Current Levetiracetam Therapy

Before adding a second agent, consider:

• The current levetiracetam dose of 500 mg Q12 (1000 mg/day) is at the minimum recommended starting dose for adults, and may be suboptimal 2
• FDA labeling indicates that levetiracetam dosing can be increased up to 3000 mg/day (1500 mg Q12) for better seizure control 2
• Increasing the levetiracetam dose by 1000 mg/day every 2 weeks up to 3000 mg/day may improve seizure control before adding a second agent 2

Second-Line Agent Selection

If increasing levetiracetam is not feasible or has failed, add one of these agents:

Valproate

• Dosing: 20-30 mg/kg IV loading dose 3
• Efficacy: 46% success rate in benzodiazepine-refractory status epilepticus 1
• Advantages: High success rate (88%) in some studies 3
• Adverse effects: GI disturbances, tremor 3

Fosphenytoin

• Efficacy: 45% success rate in benzodiazepine-refractory status epilepticus 1
• Advantages: Better safety profile than phenytoin with fewer local and systemic effects 3
• Adverse effects: Hypotension (3.2% risk), potential for cardiac arrhythmias 1

Monitoring and Follow-up

After adding a second agent:

• Monitor for adverse effects specific to the chosen medication
• Perform hemodynamic monitoring due to risk of hypotension, especially with fosphenytoin 3
• Conduct baseline renal and hepatic function tests, periodic electrolytes, and drug levels when appropriate 3
• Schedule follow-up every 3-6 months to assess seizure control and medication tolerability 3

Important Considerations

• Avoid phenobarbital as a first-line add-on agent due to its adverse effect profile including respiratory depression and hypotension 3
• The Established Status Epilepticus Treatment Trial (ESETT) found similar efficacy (approximately 45-47%) for levetiracetam, fosphenytoin, and valproate in status epilepticus 1
• Higher doses of levetiracetam (>40 mg/kg) have been associated with higher rates of intubation compared to lower doses 4
• The patient's home medication regimen does not affect the probability of stopping seizures with these second-line agents 1

Caveat

The evidence primarily addresses status epilepticus rather than brief seizure episodes, but the same principles of medication selection apply. The goal is to achieve seizure freedom while minimizing adverse effects that could impact quality of life.