Keppra (Levetiracetam): Detailed Explanation
Levetiracetam (Keppra) is an effective second-generation antiepileptic drug with a recommended initial dose of 1000 mg/day (500 mg twice daily) for adults with partial onset seizures, which can be increased by 1000 mg/day every 2 weeks to a maximum of 3000 mg/day. 1
Indications
- Approved as adjunctive treatment for partial onset seizures in adults and children 4 years and older with epilepsy 1
- Indicated as adjunctive therapy for myoclonic seizures in adults and adolescents 12 years and older with juvenile myoclonic epilepsy 1
- Used for adjunctive therapy in primary generalized tonic-clonic seizures in adults and children 6 years and older with idiopathic generalized epilepsy 1
- Effective in treating status epilepticus with a response rate of approximately 73% in benzodiazepine-resistant cases 2
Dosing Guidelines
Adults (16 years and older):
- Initial dose: 1000 mg/day given as 500 mg twice daily 1
- Titration: Increase by 1000 mg/day every 2 weeks 1
- Maximum recommended dose: 3000 mg/day 1
- For status epilepticus: 30 mg/kg IV at a rate of 5 mg/kg per minute 2
Pediatric Patients (4 to <16 years):
- Initial dose: 20 mg/kg/day in 2 divided doses (10 mg/kg twice daily) 1
- Titration: Increase by 20 mg/kg every 2 weeks 1
- Target dose: 60 mg/kg/day (30 mg/kg twice daily) 1
- Weight-based dosing is recommended (see table in FDA label) 1
Mechanism of Action
- Unique mechanism involving binding to synaptic vesicle protein 2A 3, 4
- Inhibits calcium release from intraneuronal stores 4
- Opposes activity of negative modulators of GABA and glycine-gated currents 4
- Inhibits excessive synchronized neuronal activity 4
- Inhibits N-type calcium channels 4
Pharmacokinetics
- Rapid and complete absorption with high oral bioavailability (nearly 100%) 4, 5
- Minimal metabolism (hydrolysis of acetamide group) 4
- Primarily eliminated through renal excretion 4
- Peak absorption time: 1 hour after oral administration 5
- Steady state achieved in 2 days with twice-daily dosing 5
- Minimal protein binding (approximately 10%) 5
- No significant drug interactions with other antiepileptic medications 4
- Lacks cytochrome P450 enzyme-inducing potential 4
Efficacy
- Clinical trials demonstrated significant reduction in seizure frequency compared to placebo 4, 6
- Approximately 15% of patients taking 1000 mg/day and 20-30% of patients taking 3000 mg/day achieve ≥50% reduction in seizure frequency 6
- In status epilepticus, levetiracetam shows efficacy rates of 67-73% when used after benzodiazepines 7
- In elderly patients with documented status epilepticus, 89% showed reduction in seizures and 78% had complete cessation after receiving 1,500 mg 2
- Extended-release formulation (Keppra XR) allows for once-daily dosing with similar efficacy 8
Adverse Effects
- Most common side effects: somnolence, dizziness, infection, and asthenia 5
- Most adverse events are mild to moderate in severity 4
- Not associated with cognitive impairment or drug-induced weight gain 4
- May cause behavioral adverse effects in some patients 4
- Dizziness (OR 2.36) and infection (OR 1.82) are significantly associated with levetiracetam use 6
- Generally well-tolerated compared to other antiepileptic drugs 6
Administration Considerations
- Can be taken with or without food 1
- Available in immediate-release and extended-release formulations 8
- Extended-release formulation offers better tolerance and increased compliance 8
- For oral solution, a calibrated measuring device should be used 1
Special Populations
- Dosage adjustment may be necessary in patients with renal impairment 1
- Safety established in pediatric populations with age-appropriate dosing 1
- Effective in elderly patients with status epilepticus 2
Levetiracetam represents an important option in the antiepileptic armamentarium due to its unique mechanism of action, favorable pharmacokinetic profile, and demonstrated efficacy across multiple seizure types.