Effect of 500 mg Keppra (Levetiracetam) Given Five Hours Apart
Administering 500 mg of levetiracetam five hours apart is likely to provide subtherapeutic blood levels and insufficient seizure protection for most patients, as the standard dosing interval should be 12 hours to maintain therapeutic concentrations. 1
Pharmacokinetic Considerations
Levetiracetam has the following key pharmacokinetic properties that affect its administration schedule:
- Half-life: 7 ± 1 hour in adults (unaffected by dose or repeated administration) 2
- Absorption: Rapid and almost complete oral absorption with peak concentrations occurring in about 1 hour 2
- Bioavailability: 100% oral bioavailability 2
- Metabolism: Minimal metabolism (24% of dose) through enzymatic hydrolysis 2
- Elimination: Primarily renal excretion (66% of dose as unchanged drug) 2
Therapeutic Implications of the Proposed Dosing
Subtherapeutic Levels
When administering 500 mg doses five hours apart:
- The first 500 mg dose would begin to be eliminated before the second dose reaches peak concentration
- Standard maintenance dosing for adults is typically 1000 mg every 12 hours 1
- With only a 5-hour interval, the patient would experience significant fluctuations in blood levels
Seizure Protection
- Therapeutic serum concentrations are typically 10-37 μg/mL 3
- A single 1500 mg loading dose can achieve serum concentrations of approximately 30 μg/mL within 1-2 hours 4
- Two 500 mg doses given 5 hours apart would likely not maintain therapeutic levels consistently
Potential Adverse Effects
Even with this suboptimal dosing schedule, the patient may experience:
- Somnolence (10.5-15.2% of patients) 1
- Asthenia (weakness)
- Dizziness
- Irritability or behavioral changes (especially in patients with prior psychiatric history) 1
Proper Dosing Recommendations
For effective seizure control:
- Initial therapy: Loading dose of 1000-1500 mg, followed by maintenance doses of 500-1000 mg every 12 hours 1
- Maintenance therapy: 1000-3000 mg daily in two divided doses (every 12 hours) 2
- Children: Dosing based on weight (30 mg/kg/day divided into two doses) 1
Special Considerations
- Renal impairment: Dose adjustment required based on creatinine clearance 2
- Elderly patients: May require lower doses due to decreased renal clearance 2
- Pediatric patients: In children 4-12 years, the half-life is approximately 5 hours 2
Clinical Implications
The proposed dosing schedule (500 mg five hours apart) would result in:
- Inadequate seizure protection due to subtherapeutic levels
- Potential for breakthrough seizures
- Unnecessary fluctuations in blood levels that could increase side effects
- Missed opportunity for optimal therapeutic benefit
For proper seizure management, the dosing interval should be extended to 12 hours, and depending on the patient's needs, the dose may need to be increased to 1000 mg per administration.