What is the maintenance dose of levetiracetam (Keppra) for a patient with non-convulsive seizures who is already taking 2g daily?

Maintenance Dose of Levetiracetam in Non-Convulsive Seizures

For a patient already taking 2g daily of levetiracetam with non-convulsive seizures, the maintenance dose should be 15 mg/kg (maximum 1,500 mg) IV every 12 hours after resolution of status epilepticus, or continue the current oral dose of 1000 mg twice daily if seizures are controlled. 1

Context-Specific Dosing for Non-Convulsive Status Epilepticus

The distinction between convulsive and non-convulsive status epilepticus is critical for maintenance dosing:

• Non-convulsive status epilepticus: 15 mg/kg (maximum 1,500 mg) IV every 12 hours 1, 2
• Convulsive status epilepticus: 30 mg/kg IV every 12 hours OR increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) IV every 12 hours (maximum 1,500 mg) 1, 2

This represents a significant difference—non-convulsive status epilepticus requires half the maintenance dose of convulsive status epilepticus. 1

Clinical Decision Algorithm

If the patient is experiencing breakthrough non-convulsive seizures on 2g daily:

1. First, verify compliance and check serum levetiracetam levels to ensure therapeutic dosing before escalating 2

2. Optimize current levetiracetam dose up to the maximum of 3000 mg/day (1500 mg twice daily) before adding another agent 2, 3

   • The FDA label indicates that doses of 1000 mg, 2000 mg, and 3000 mg daily given as twice-daily dosing have been shown effective 3
   • Doses greater than 3000 mg/day have been used in open-label studies but show no evidence of additional benefit 3

3. If seizures persist despite optimization, consider adding a second agent such as valproate or lamotrigine rather than exceeding 3000 mg/day 2

Standard Maintenance Dosing for Chronic Epilepsy

For ongoing seizure management (not acute status epilepticus):

• Adults: Treatment should be initiated at 1000 mg/day (500 mg BID), with incremental increases of 1000 mg/day every 2 weeks to a maximum of 3000 mg/day 3
• Current dose of 2000 mg/day is within therapeutic range and represents a mid-range maintenance dose 3
• Approximately 15% of patients taking 1000 mg and 20-30% taking 3000 mg daily achieve 50% or greater reduction in seizure frequency 4

Important Monitoring Considerations

Therapeutic drug monitoring is essential when seizures are not controlled: 2

• Peak concentrations typically range from 26.5-39.8 μg/ml 5
• Trough concentrations typically range from 13.9-18.2 μg/ml 5
• Elimination half-life ranges from 8.7-10.1 hours in patients with normal renal function 5

Search for precipitating factors before escalating dose: 2

• Sleep deprivation
• Alcohol use
• Medication non-compliance
• Intercurrent illness
• Consider EEG to distinguish true epileptic seizures from psychogenic seizures or detect subclinical activity 2

Special Populations and Dose Adjustments

Renal dysfunction requires dose reduction: 5

• Levetiracetam is primarily renally cleared (66% unchanged in urine) 6
• For patients on continuous venovenous hemofiltration (CVVH), consider 1000 mg every 12 hours with therapeutic drug monitoring 5

The current 2g daily dose does not require adjustment unless:

• Renal function is impaired
• Seizures remain uncontrolled despite confirmed compliance
• Adverse effects develop (somnolence, dizziness, asthenia) 6, 7

Common Pitfalls to Avoid

Do not exceed 3000 mg/day without clear justification, as no additional benefit has been demonstrated and this only increases adverse effect risk 3, 4

Do not add a second anticonvulsant before optimizing levetiracetam to maximum tolerated dose, as combination therapy increases drug interactions, adverse events, and complexity affecting compliance 2

Do not assume seizure breakthrough represents treatment failure without first confirming compliance and checking serum levels, as non-compliance is a common cause of breakthrough seizures 2