What is Keppra (levetiracetam) used for?

What is Keppra (Levetiracetam) Used For?

Keppra (levetiracetam) is an antiepileptic medication FDA-approved as adjunctive (add-on) therapy for three specific seizure types: partial-onset seizures in patients ≥4 years old, myoclonic seizures in juvenile myoclonic epilepsy for patients ≥12 years old, and primary generalized tonic-clonic seizures in idiopathic generalized epilepsy for patients ≥6 years old. 1

FDA-Approved Indications

Levetiracetam has three distinct FDA-approved uses, all as adjunctive therapy 1:

• Partial-onset seizures (with or without secondary generalization) in adults and children ≥4 years of age with epilepsy 1
• Myoclonic seizures in adults and adolescents ≥12 years of age with juvenile myoclonic epilepsy 1
• Primary generalized tonic-clonic seizures in adults and children ≥6 years of age with idiopathic generalized epilepsy 1

Off-Label Use in Status Epilepticus

Beyond its FDA-approved indications, levetiracetam has become a widely used second-line agent for status epilepticus refractory to benzodiazepines 2:

• The American College of Emergency Physicians recommends levetiracetam 30 mg/kg IV over 5 minutes as a second-line option for benzodiazepine-refractory status epilepticus, with demonstrated efficacy of 68-73% 2, 3
• This efficacy is comparable to valproate (68% vs 73%) when both are used at 30 mg/kg IV 3
• Levetiracetam offers significant advantages in the acute setting: minimal cardiovascular effects, no hypotension risk (compared to 12% with fosphenytoin), and no requirement for cardiac monitoring 2, 3

Clinical Efficacy Evidence

The drug has demonstrated robust efficacy across multiple seizure types 4, 5:

• Adjunctive therapy for refractory partial-onset seizures significantly reduces seizure frequency compared to placebo in both pediatric and adult patients 4, 5
• Monotherapy for newly diagnosed partial-onset seizures shows non-inferiority to carbamazepine controlled-release 4, 5
• Idiopathic generalized epilepsy with myoclonic or generalized tonic-clonic seizures responds well to adjunctive levetiracetam 4, 5, 6

Unique Pharmacological Profile

Levetiracetam stands apart from other antiepileptic drugs due to several key characteristics 4, 5, 7:

• Novel mechanism of action involving binding to synaptic vesicle protein 2A (SV2A), inhibiting N-type calcium channels, and modulating intraneuronal calcium release 4, 5, 7
• Minimal drug interactions because it lacks cytochrome P450 enzyme-inducing potential and undergoes minimal metabolism 4, 5, 7
• Favorable pharmacokinetics with rapid and complete absorption, high oral bioavailability, <10% protein binding, and primarily renal elimination 4, 5, 7
• No cognitive impairment or weight gain, though behavioral adverse effects can occur in some patients 4, 5

Practical Dosing Considerations

For chronic seizure management, levetiracetam should be initiated at 1000 mg/day (500 mg twice daily) with gradual titration to effective doses 8. In the emergency setting for status epilepticus, the loading dose is 30 mg/kg IV over 5 minutes, with lower doses (20 mg/kg) showing reduced efficacy of only 38% 3.

Important Clinical Caveats

• Behavioral adverse effects can occur, particularly in patients with learning disabilities, manifesting as irritability or mood changes 4, 6
• Dose adjustment required in renal dysfunction due to primarily renal elimination 2
• Common adverse effects include somnolence, asthenia, dizziness, and fatigue, though overall tolerability is generally excellent 4, 5, 9
• Does not interact with oral contraceptives, simplifying treatment in women of childbearing age 6