What are the guidelines for dosing and monitoring Keppra (levetiracetam) in patients?

Keppra (Levetiracetam) Dosing and Monitoring

Standard Maintenance Dosing

For adults with partial onset seizures, start levetiracetam at 1000 mg/day (500 mg twice daily), increasing by 1000 mg/day every 2 weeks to a maximum of 3000 mg/day, with no evidence that doses above 3000 mg/day provide additional benefit. 1

Adults (≥16 years)

Partial Onset Seizures:

• Initial dose: 500 mg twice daily (1000 mg/day total) 1
• Titration: Increase by 1000 mg/day every 2 weeks 1
• Target dose: 3000 mg/day (1500 mg twice daily) 1
• Maximum: 3000 mg/day for routine use; doses above this show no additional benefit 1

Myoclonic Seizures (Juvenile Myoclonic Epilepsy, ≥12 years):

• Initial dose: 1000 mg/day (500 mg twice daily) 1
• Target dose: 3000 mg/day; lower doses have not been adequately studied 1

Primary Generalized Tonic-Clonic Seizures:

• Same dosing as myoclonic seizures 1

Pediatric Dosing

Children 4 to <16 years (Partial Onset Seizures):

• 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); mean dose in trials was 52 mg/kg 1
• Weight-based guidance: Children ≤20 kg should use oral solution; >20 kg can use tablets or solution 1

Children 6 to <16 years (Primary Generalized Tonic-Clonic Seizures):

• Same weight-based dosing as partial onset seizures 1

---

Loading Dose Strategies

Status Epilepticus - Adults

For status epilepticus in adults, administer 30-60 mg/kg IV (maximum 4500 mg) at a rate of 100 mg/min as a second-line agent after benzodiazepines. 2

• Recommended loading dose: 30-60 mg/kg IV (maximum 4500 mg) at 100 mg/min 2
• Alternative dosing: 30-50 mg/kg IV or fixed dosing of 1500-3000 mg IV 2
• Higher doses: Up to 60 mg/kg (maximum 4500 mg) are safe and well-studied 3
• Advantages: No cardiac monitoring required (unlike phenytoin/fosphenytoin) and minimal drug interactions 2

Status Epilepticus - Pediatrics

For convulsive status epilepticus in children, the American Academy of Pediatrics recommends 40 mg/kg IV bolus (maximum 2500 mg) in addition to benzodiazepines. 4

• Convulsive status epilepticus: 40 mg/kg IV bolus (maximum 2500 mg) 4
• Non-convulsive status epilepticus: 40 mg/kg IV bolus (maximum 2500 mg) 4
• Neonates: 10 mg/kg IV 2
• Infusion time: 10-20 minutes in pediatric patients 2
• Maintenance after loading:
  • Non-convulsive SE: 15 mg/kg IV every 12 hours (maximum 1500 mg) 4
  • Convulsive SE: 30 mg/kg IV every 12 hours (maximum 1500 mg per dose) 4

Seizure Prophylaxis/Resumption of Therapy

For seizure prophylaxis or resuming therapy in patients with known seizure disorders, a 1500 mg oral or IV loading dose is well-established and safe. 3

• Standard loading: 1500 mg IV or oral 3
• Achieves therapeutic levels rapidly without significant adverse effects 3

---

Special Populations

Renal Impairment

Levetiracetam dosing must be adjusted based on creatinine clearance, as the drug is primarily renally eliminated. 1

Creatinine Clearance	Dosage Range	Frequency
Normal (>80 mL/min)	500-1500 mg	Every 12 hours
Mild (50-80 mL/min)	500-1000 mg	Every 12 hours
Moderate (30-50 mL/min)	250-750 mg	Every 12 hours
Severe (<30 mL/min)	250-500 mg	Every 12 hours
ESRD on dialysis	500-1000 mg*	Every 24 hours

*Following dialysis, give 250-500 mg supplemental dose 1

Augmented Renal Clearance (ARC) in Critically Ill

In critically ill patients with augmented renal clearance, the standard 500 mg twice daily starting dose is inadequate; at least 1500 mg twice daily is recommended. 5

• Prevalence of ARC: 30-90% in critically ill patients 5
• Pharmacokinetic changes: Elevated clearance up to 6.5 L/h (vs. 3.8 L/h in healthy individuals), lower trough concentrations 5
• Recommended starting dose: 1500 mg twice daily for patients with ARC 5
• Monitoring: Careful monitoring of creatinine clearance is essential 5

CAR T-Cell Therapy Seizure Prophylaxis

For seizure prophylaxis following CAR T-cell therapy, administer levetiracetam 500-750 mg orally every 12 hours for 30 days starting on the day of infusion. 6

• Dose: 500-750 mg orally every 12 hours 6
• Duration: 30 days 6
• Indication: Prophylaxis only, not treatment of active seizures 4
• Rationale: Used especially for CAR T-cell therapies with higher neurotoxicity risk (e.g., axicabtagene, brexucabtagene) 6

---

Monitoring Requirements

Routine Monitoring

Levetiracetam does not require therapeutic drug monitoring in most cases, but complete blood count should be monitored periodically. 6

• No therapeutic drug monitoring needed for routine use 6
• Monitor complete blood count periodically 6
• No cardiac monitoring required during IV administration 2
• Baseline and periodic assessments: Consider in specific clinical contexts (e.g., status epilepticus, critically ill patients) 5

Clinical Monitoring

• Adverse effects to monitor: Somnolence, asthenia, dizziness, headache, fatigue 1, 7, 8
• Dose-dependent effects: Somnolence and asthenia increase with higher doses (especially at 4000 mg/day) 7
• Behavioral changes: Monitor for CNS depression, irritability, confusion, depression 6

---

Administration Considerations

Route and Timing

• Can be given with or without food 1
• IV administration rate: Maximum 100 mg/min to minimize adverse effects 2
• Rapid IV push: Undiluted rapid IV push up to 4500 mg is safe in status epilepticus 3
• Subcutaneous route: Emerging evidence supports subcutaneous administration (500-4000 mg daily) for end-of-life care, using 1:1 oral-to-subcutaneous conversion 9

Common Pitfalls to Avoid

Do not underdose in status epilepticus—use the full 40 mg/kg loading dose rather than lower prophylactic doses. 4

• Avoid underdosing in status epilepticus: Use full loading doses (40 mg/kg in pediatrics, 30-60 mg/kg in adults) 4
• Do not delay administration due to concerns about dilution; rapid undiluted IV push is safe 3
• Adjust for renal function: Failure to adjust doses in renal impairment or ARC leads to subtherapeutic or toxic levels 1, 5
• Continue maintenance dosing: After seizure termination in status epilepticus, continue maintenance for at least 3 doses of benzodiazepines plus ongoing levetiracetam 4
• Use calibrated measuring devices for oral solution, not household spoons 1

---

Efficacy Considerations

• Responder rates (≥50% seizure reduction): Dose-dependent, with higher rates at 2000 mg/day vs. 1000 mg/day 8
• Seizure freedom rates: 5.5-6.3% at maintenance doses of 1000-2000 mg/day 8
• Status epilepticus efficacy: 67-73% efficacy at 20-30 mg/kg, comparable to valproate 3
• Dose-response: While some studies show trends toward greater response with higher doses, a consistent dose-response above 3000 mg/day has not been demonstrated 1