Levetiracetam XR (Keppra XR) Dosing for Epilepsy
For adult patients with epilepsy, Levetiracetam XR should be initiated at 1000 mg once daily and can be titrated up to a maximum recommended dose of 3000 mg once daily, with dosage increases of 1000 mg every 2 weeks based on clinical response and tolerability. 1
Adult Dosing (16 years and older)
Partial Onset Seizures
- Initial dose: 1000 mg once daily
- Titration: Increase by 1000 mg every 2 weeks as needed
- Recommended maintenance dose: 1000-3000 mg once daily
- Maximum dose: 3000 mg once daily
Myoclonic Seizures (12 years and older with juvenile myoclonic epilepsy)
- Initial dose: 1000 mg once daily
- Titration: Increase by 1000 mg every 2 weeks
- Recommended maintenance dose: 3000 mg once daily
Primary Generalized Tonic-Clonic Seizures
- Initial dose: 1000 mg once daily
- Titration: Increase by 1000 mg every 2 weeks
- Recommended maintenance dose: 3000 mg once daily
Pediatric Dosing (4 to <16 years)
For children, the immediate-release formulation is recommended with twice-daily dosing:
- Initial dose: 20 mg/kg/day divided into two doses (10 mg/kg twice daily)
- Titration: Increase by 20 mg/kg every 2 weeks
- Recommended maintenance dose: 60 mg/kg/day divided into two doses (30 mg/kg twice daily)
Administration Considerations
- Levetiracetam XR can be taken with or without food 1
- Only whole tablets should be administered (do not break, crush, or chew extended-release tablets)
- For patients who cannot swallow tablets, the immediate-release formulation should be used
Efficacy and Dose-Response Relationship
Clinical studies have demonstrated a dose-dependent efficacy of Levetiracetam:
- At 1000 mg/day: Significant reduction in seizure frequency compared to placebo 2
- At 2000 mg/day: Greater response rate compared to 1000 mg/day in within-patient comparisons 2
- At 3000 mg/day: Recommended for myoclonic seizures and primary generalized tonic-clonic seizures 1
Special Populations
Renal Impairment
- Dose adjustment is necessary based on creatinine clearance
- For patients on dialysis, supplemental doses may be required following dialysis
Elderly
- Start at lower doses and titrate more slowly due to potential for decreased renal function
Common Adverse Effects
The most frequently reported adverse events with Levetiracetam XR include:
- Somnolence
- Irritability
- Dizziness
- Nausea
- Influenza
- Nasopharyngitis 3
Clinical Pearls
- Levetiracetam XR allows for once-daily dosing, which may improve medication adherence 3
- The extended-release formulation provides relatively constant plasma concentrations, which may minimize concentration-related adverse effects 3
- Levetiracetam has minimal drug-drug interactions and does not affect the serum levels of other antiepileptic medications 4
- High retention rates (approximately 80-85%) have been observed in clinical studies, indicating good tolerability 5, 6
- Seizure freedom rates of 5.5-6.3% have been reported at doses of 1000-2000 mg/day 2
Monitoring
- No routine blood level monitoring is required due to Levetiracetam's wide therapeutic index and linear pharmacokinetics 3
- Monitor for behavioral changes, particularly irritability and aggression
- Assess seizure frequency and adverse effects at each follow-up visit
Levetiracetam XR's favorable pharmacokinetic profile, including minimal protein binding (<10%), linear kinetics, and minimal metabolism through pathways independent of the cytochrome P450 system, makes it an excellent option for adjunctive therapy in epilepsy management 3.