What is Keppra (Levetiracetam)?
Keppra (levetiracetam) is a second-generation antiepileptic drug with a unique chemical structure, approved by the FDA as adjunctive therapy for partial onset seizures, myoclonic seizures in juvenile myoclonic epilepsy, and primary generalized tonic-clonic seizures. 1
Chemical Structure and Mechanism
Levetiracetam is chemically described as (-)-(S)-α-ethyl-2-oxo-1-pyrrolidine acetamide (molecular formula C8H14N2O2), making it structurally unrelated to existing antiepileptic drugs. 1
The precise mechanism of action involves binding to synaptic vesicle protein 2A (SV2A), which modulates synaptic neurotransmitter release, and targeting high-voltage N-type calcium channels. 2, 3
FDA-Approved Indications
Partial onset seizures: Adjunctive therapy in adults and children ≥4 years of age with epilepsy. 1
Myoclonic seizures: Adjunctive therapy in adults and adolescents ≥12 years with juvenile myoclonic epilepsy. 1
Primary generalized tonic-clonic seizures: Adjunctive therapy in adults and children ≥6 years with idiopathic generalized epilepsy. 1
Pharmacokinetic Profile
Levetiracetam has nearly ideal pharmacokinetic properties that distinguish it from other antiepileptic drugs:
Absorption: Rapidly and almost completely absorbed after oral ingestion with excellent bioavailability. 2, 4
Protein binding: Less than 10% protein-bound, minimizing drug interaction potential. 2
Metabolism: Minimally metabolized through a pathway independent of the cytochrome P450 system, with no induction of its own metabolism. 2, 4
Elimination: Predominantly eliminated as unchanged drug in the urine. 5
Kinetics: Demonstrates linear kinetics with rapid achievement of steady-state concentrations and a wide therapeutic index. 2, 4
Drug interactions: No clinically significant drug-drug interactions with other anticonvulsants, digoxin, warfarin, probenecid, or oral contraceptives. 6, 4
Clinical Use in Status Epilepticus
Beyond its FDA-approved indications, levetiracetam has become a cornerstone second-line agent for status epilepticus:
Dosing for status epilepticus: The American College of Emergency Physicians recommends 30 mg/kg IV over 5 minutes as a second-line agent after benzodiazepine failure. 7, 8
Efficacy: Demonstrates 68-73% seizure control rates in benzodiazepine-refractory status epilepticus, comparable to valproate (46-47%) and superior to phenobarbital (58.2%). 7, 8
Safety advantage: Minimal cardiovascular effects with no hypotension risk, unlike fosphenytoin (12% hypotension risk) or pentobarbital (77% hypotension risk). 7, 9
Monitoring requirements: Can be administered without cardiac monitoring requirements, making it particularly suitable for elderly patients. 7
Adverse Effect Profile
Common adverse events: Somnolence, asthenia, dizziness, headache, irritability, nausea, influenza, and nasopharyngitis. 2, 6
Behavioral effects: Irritability, agitation, anger, and aggressive behavior occur in approximately 12-15% of patients, with higher risk in learning-disabled individuals, those with prior psychiatric history, and those with symptomatic generalized epilepsy. 5
Laboratory effects: Slight trends toward lower white and red blood cell counts have been detected, though no organ toxicity has been described with patient exposures exceeding 500,000. 5
Discontinuation rates: In major trials, 6.9-10.9% of levetiracetam-treated patients discontinued due to adverse events compared to 5.3-8.6% for placebo. 5
Formulations Available
Immediate release tablets: Available as 500 mg oblong yellow tablets containing levetiracetam with inactive ingredients including colloidal silicon dioxide, corn starch, hydroxypropyl methylcellulose, and others. 1
Extended release formulation (Keppra XR): Approved for once-daily dosing in patients ≥16 years, which may increase compliance and minimize concentration-related adverse effects through relatively constant plasma concentrations. 2, 3
Other formulations: Available as liquid formulation for oral ingestion and intravenous concentrated solution. 4
Critical Clinical Advantages
Rapid onset of action: Makes it optimal for treating epilepsy associated with other medical conditions and for acute seizure management. 4
No tolerance development: Efficacy appears maintained in long-term studies with no evidence of tolerance. 5
Broad spectrum activity: Effective against partial-onset seizures, primary generalized tonic-clonic seizures, and myoclonic seizures. 4, 3