Levetiracetam (Keppra) Management Guidelines
Levetiracetam is an effective antiepileptic medication with a favorable safety profile that can be administered at doses of 1000-3000 mg/day for most adults with seizure disorders, with dose adjustments based on renal function and clinical response. 1
Indications
- Adjunctive therapy for partial onset seizures in adults and children ≥4 years 2
- Adjunctive therapy for myoclonic seizures in adults and adolescents ≥12 years with juvenile myoclonic epilepsy 2
- Adjunctive therapy for primary generalized tonic-clonic seizures in patients ≥6 years with idiopathic generalized epilepsy 2
- Seizure prophylaxis in patients with CNS disease or history of seizures receiving CAR T-cell therapy 1
Dosing Guidelines
Standard Dosing
- Initial dose: 500 mg twice daily for adults 1
- Titration: Increase by 1000 mg/day every 2 weeks as needed 2
- Maintenance dose: 1000-3000 mg/day in two divided doses 2, 3
- Maximum recommended dose: 3000 mg/day for adults 3
- Loading dose: 1500 mg orally or up to 60 mg/kg IV for rapid initiation 1
Special Populations
- Renal impairment: Dose adjustment required based on creatinine clearance 2
- Elderly: Start at lower doses and titrate more slowly due to potential for increased sensitivity 2
- Pediatric dosing:
Emergency/Status Epilepticus
- Loading dose: 30-50 mg/kg IV at a rate of 100 mg/min 1
- Efficacy: 67-73% seizure termination rate in refractory status epilepticus 1
Administration Routes
- Oral: Tablets or solution, twice daily dosing 2
- Intravenous: Can be administered at rates up to 100 mg/min 1
- Subcutaneous: May be used in palliative care settings with 1:1 oral-to-subcutaneous conversion ratio 4
Monitoring
Laboratory Monitoring
- Complete blood count: Monitor for minor decreases in RBC, hemoglobin, and WBC 2
- Liver function tests: Not routinely required as significant LFT abnormalities are rare 2
Clinical Monitoring
- Efficacy: Assess seizure frequency and severity 5
- Neurological status: Monitor for changes in mental status, especially when used for status epilepticus 1
- Behavioral changes: Watch for aggression, agitation, depression, or psychotic symptoms 2
Adverse Effects
Common Adverse Effects
Serious Adverse Effects
- Behavioral abnormalities and psychotic symptoms (rare) 2
- Hematologic abnormalities (minor decreases in WBC, neutrophils) 2
- Suicidal thoughts and behavior (class effect of antiepileptic drugs) 2
Drug Interactions
- Minimal drug interactions due to limited hepatic metabolism 2
- Does not affect the pharmacokinetics of other antiepileptic drugs 2
- No significant interactions with oral contraceptives, digoxin, or warfarin 2
Special Considerations
Status Epilepticus Management
- Levetiracetam can be considered as an alternative to phenytoin/fosphenytoin for refractory status epilepticus 1
- Advantages include rapid administration and fewer adverse effects compared to phenytoin 1
- No cardiac monitoring required during administration 1
CAR T-Cell Therapy
- Recommended for seizure prophylaxis in patients receiving CAR T-cell therapy who have CNS disease or history of seizures 1
- Dosing: 10 mg/kg (maximum 500 mg per dose) every 12 hours for 30 days following infusion 1
- Well-tolerated with minimal risk of adverse drug interactions in this population 1
Withdrawal Considerations
- No evidence of typical withdrawal-related adverse events or rebound phenomena 5
- Gradual tapering recommended for long-term therapy 2
Overdose Management
- Generally well-tolerated even in significant overdose (up to 358 mg/kg reported) 6
- Most overdoses result in mild symptoms (somnolence, dizziness) 6
- Rare cases may require respiratory support, so clinical vigilance is still necessary 6