What is the recommended use and dosage of Keppra (levetiracetam) for patients with epilepsy?

Levetiracetam (Keppra) for Epilepsy: Recommended Use and Dosing

Primary Indications

Levetiracetam is FDA-approved as adjunctive therapy for partial-onset seizures (ages ≥4 years), myoclonic seizures in juvenile myoclonic epilepsy (ages ≥12 years), and primary generalized tonic-clonic seizures (ages ≥6 years). 1

Approved Uses:

• Adjunctive treatment for partial-onset seizures with or without secondary generalization in adults and children ≥4 years 1
• Adjunctive therapy for myoclonic seizures in patients ≥12 years with juvenile myoclonic epilepsy 1
• Adjunctive therapy for primary generalized tonic-clonic seizures in patients ≥6 years with idiopathic generalized epilepsy 1

Standard Dosing for Chronic Epilepsy Management

Adults (≥16 years) with Partial-Onset Seizures:

Start with 1000 mg/day divided as 500 mg twice daily, then increase by 1000 mg/day every 2 weeks up to a maximum of 3000 mg/day. 1

• Initial dose: 500 mg twice daily 1
• Titration: Increase by 1000 mg/day increments every 2 weeks 1
• Target dose: 3000 mg/day (1500 mg twice daily) 1
• Doses >3000 mg/day provide no additional benefit 1
• Median effective dose in clinical practice: 1000 mg/day 2

Pediatric Patients (4 to <16 years) with Partial-Onset Seizures:

Start with 20 mg/kg/day divided twice daily (10 mg/kg BID), increase by 20 mg/kg every 2 weeks to target dose of 60 mg/kg/day (30 mg/kg BID). 1

• Initial: 10 mg/kg twice daily 1
• Target: 30 mg/kg twice daily (maximum 60 mg/kg/day) 1
• If 60 mg/kg/day not tolerated, reduce dose 1
• Patients ≤20 kg: use oral solution 1
• Patients >20 kg: tablets or oral solution acceptable 1

Myoclonic Seizures (≥12 years):

Start with 1000 mg/day (500 mg BID), increase by 1000 mg/day every 2 weeks to target dose of 3000 mg/day. 1

• Doses <3000 mg/day have not been adequately studied for this indication 1

Primary Generalized Tonic-Clonic Seizures:

Adults (≥16 years): Start 1000 mg/day (500 mg BID), increase by 1000 mg/day every 2 weeks to 3000 mg/day. 1

Pediatric (6 to <16 years): Start 20 mg/kg/day (10 mg/kg BID), increase by 20 mg/kg every 2 weeks to 60 mg/kg/day. 1

Acute Status Epilepticus Dosing

Second-Line Agent (After Benzodiazepines):

Administer 30 mg/kg IV over 5 minutes for benzodiazepine-refractory status epilepticus, with 68-73% efficacy and minimal cardiovascular effects. 3, 4

• Loading dose: 30 mg/kg IV over 5 minutes 3, 5
• Alternative studied doses: 1500-2500 mg IV over 5 minutes 5
• Lower doses (20 mg/kg) show reduced efficacy (38%) and are not recommended 5
• No cardiac monitoring required (unlike phenytoin/fosphenytoin) 3
• 0% hypotension risk (compared to 12% with fosphenytoin) 3, 4

Maintenance After Status Epilepticus:

Continue 30 mg/kg IV every 12 hours OR increase prophylaxis dose by 10 mg/kg (to 20 mg/kg) IV every 12 hours (maximum 1500 mg). 3

Efficacy Data

Chronic Epilepsy:

• Adjunctive therapy reduces seizure frequency significantly more than placebo in refractory partial-onset seizures 6, 7
• Approximately 50% of patients achieve seizure freedom on median dose of 1000 mg/day when used as monotherapy 2
• Each 1000 mg dose increase raises odds of response by 40% 4
• 500 mg/day is NOT more effective than placebo 4
• Seizure freedom more likely when used as first monotherapy (54.4%) versus switching from another AED (39.2%) 2

Status Epilepticus:

• 68-73% efficacy for benzodiazepine-refractory seizures 3, 4, 5
• Similar efficacy to valproate (73% vs 68% seizure cessation) when both used at 30 mg/kg 5

Adverse Effects Profile

Common Side Effects:

• Behavioral changes occur in 23% of children 4
• Neuropsychiatric symptoms: aggression, mood swings, irritability, depression (7.9% discontinuation rate) 2
• Dizziness, fatigue, infection 8, 6
• NOT associated with cognitive impairment or weight gain 6, 7

Serious Adverse Effects:

• Approximately 16% discontinue due to side effects, with 50% of these being neuropsychiatric symptoms 2
• Transient irritability, imbalance, tiredness, lightheadedness (11% in loading studies) 8

Key Clinical Advantages

Levetiracetam offers significant practical advantages over traditional antiepileptics:

• No cytochrome P450 interactions - safe with other medications 6, 7
• Rapid and complete oral absorption with high bioavailability 6, 7
• Minimal metabolism (hydrolysis only, primarily renal elimination) 6, 7
• No cardiac monitoring required during IV administration 3
• Can be given orally or IV without food restrictions 1

Position in Treatment Algorithm

For New-Onset Epilepsy:

Levetiracetam is noninferior to carbamazepine for newly diagnosed partial-onset seizures and can be used as first-line monotherapy. 6, 7

For Status Epilepticus:

Use as second-line agent after benzodiazepines fail, alongside valproate, fosphenytoin, or phenobarbital as equivalent options. 3

• First-line: Benzodiazepines (lorazepam 4 mg IV) 3
• Second-line: Levetiracetam 30 mg/kg IV over 5 minutes 3, 5
• Do NOT use as third-line after both benzodiazepines AND phenytoin/valproate - evidence less clear 5

Critical Pitfalls to Avoid

• Never use 500 mg/day as maintenance - this dose is ineffective 4
• Do not underdose in status epilepticus - 20 mg/kg shows only 38% efficacy; use full 30 mg/kg 5
• Monitor for behavioral changes, especially in children and patients with pre-existing psychiatric conditions 4, 2
• Adjust dose in renal dysfunction - primarily renally eliminated 6, 7
• Do not skip second-line agents in status epilepticus to jump directly to anesthetic agents 3

Administration Considerations

• Can be given with or without food 1
• Use calibrated measuring device for oral solution, not household spoons 1
• Whole tablets only - do not split or crush 1
• IV administration over 5 minutes for status epilepticus 3, 5
• Rapid IV loading up to 60 mg/kg has been well tolerated in epilepsy monitoring units 8, 5