What are the indications for prescribing Levetiracetam and Sodium Valproate?

Indications for Prescribing Levetiracetam and Sodium Valproate

Levetiracetam and sodium valproate are indicated for different types of seizures, with levetiracetam showing better tolerability in most patient populations while sodium valproate remains the first-line treatment for generalized seizures. 1, 2

Levetiracetam Indications

Levetiracetam is FDA-approved for:

1. Adjunctive treatment of partial onset seizures:

   • Adults and children 4 years of age and older with epilepsy 1
   • Starting dose: 1000 mg/day (500 mg BID) in adults; 20 mg/kg/day in children
   • Maximum recommended dose: 3000 mg/day in adults; 60 mg/kg/day in children

2. Adjunctive therapy for myoclonic seizures:

   • Adults and adolescents 12 years and older with juvenile myoclonic epilepsy 1
   • Recommended dose: 3000 mg/day

3. Adjunctive therapy for primary generalized tonic-clonic seizures:

   • Adults and children 6 years and older with idiopathic generalized epilepsy 1
   • Recommended dose: 3000 mg/day in adults; 60 mg/kg/day in children

4. Monotherapy for partial onset seizures (European indication, not FDA-approved in US) 3

Sodium Valproate Indications

Sodium valproate is indicated for:

1. First-line treatment for generalized onset seizures:

   • Particularly effective for generalized tonic-clonic seizures 2
   • High-certainty evidence shows sodium valproate performs better than other AEDs for generalized onset seizures 2

2. Status epilepticus:

   • Comparable efficacy to levetiracetam and fosphenytoin in status epilepticus 4
   • Median time to seizure termination: 7.0 minutes (faster than levetiracetam at 10.5 minutes) 4

Comparative Efficacy and Safety

Focal Seizures

• For focal onset seizures, lamotrigine and levetiracetam show the best profiles in terms of treatment failure and seizure control as first-line treatments 2
• Carbamazepine remains a standard first-line option for focal seizures 2

Generalized Seizures

• Sodium valproate has the best profile for generalized tonic-clonic seizures compared to all other treatments 2
• Lamotrigine and levetiracetam are suitable alternatives when sodium valproate is contraindicated 2

Pediatric Considerations

• Recent evidence suggests levetiracetam may be more effective and better tolerated than sodium valproate in children with epilepsy:

  • Seizure control: 85% with levetiracetam vs. 73% with sodium valproate (p=0.037) 5
  • Absence of side effects: 31% with levetiracetam vs. 10% with sodium valproate (p=0.012) 5
  • Weight gain: 5% with levetiracetam vs. 16% with sodium valproate 5

• In ASM-naïve pediatric patients with idiopathic generalized epilepsy with tonic-clonic seizures, both medications showed similar efficacy:

  • Complete seizure control at 6 months: 80.64% with levetiracetam vs. 79.31% with sodium valproate 6

Key Considerations for Selection

1. Seizure type:

   • Focal seizures: Levetiracetam preferred
   • Generalized seizures: Sodium valproate preferred, with levetiracetam as alternative

2. Patient characteristics:

   • Women of childbearing potential: Levetiracetam preferred (sodium valproate has teratogenic risks)
   • Children: Levetiracetam may offer better tolerability
   • Patients with liver disease: Levetiracetam preferred (sodium valproate has hepatotoxicity risk)

3. Side effect profile:

   • Levetiracetam: Behavioral effects, minimal cognitive impairment, no weight gain 7
   • Sodium valproate: Weight gain, tremor, hepatotoxicity, teratogenicity 5

Dosing Considerations

• Levetiracetam:

  • Adults: Start with 1000 mg/day (500 mg BID), titrate by 1000 mg/day every 2 weeks to maximum 3000 mg/day 1
  • Children: Start with 20 mg/kg/day, titrate to 60 mg/kg/day 1

• Sodium valproate:

  • Children: Initial dose of 30 mg/kg/day 5
  • Effective in status epilepticus at 20-30 mg/kg IV with 88% success rate 8

Monitoring Requirements

• Regular follow-up every 3-6 months to assess seizure control and medication tolerability 8
• Laboratory monitoring including baseline renal and hepatic function, periodic electrolytes, and drug levels when appropriate 8