How to use Levetiracetam (levetiracetam)?

How to Use Levetiracetam

Levetiracetam is administered orally starting at 500 mg twice daily, with titration up to a maximum of 3000 mg/day (1500 mg twice daily) over 2-4 weeks, and is FDA-approved as adjunctive therapy for partial-onset seizures, myoclonic seizures in juvenile myoclonic epilepsy, and primary generalized tonic-clonic seizures. 1

Standard Dosing for Epilepsy

Initial Dosing and Titration

• Start with 500 mg twice daily (1000 mg total daily dose) in adults and children ≥4 years old with epilepsy 1, 2
• Titrate upward by 1000 mg/day every 2 weeks to reach the target maintenance dose 1
• Maximum dose is 3000 mg/day (1500 mg twice daily) within 4 weeks of initiation 1, 2
• Steady-state concentrations are achieved within 24-48 hours of starting therapy 3

FDA-Approved Indications

• Partial-onset seizures: Adults and children ≥4 years as adjunctive therapy 1
• Myoclonic seizures: Adults and adolescents ≥12 years with juvenile myoclonic epilepsy as adjunctive therapy 1
• Primary generalized tonic-clonic seizures: Adults and children ≥6 years with idiopathic generalized epilepsy as adjunctive therapy 1

Context-Specific Dosing

Cyclic Vomiting Syndrome (Prophylaxis)

• Starting dose: 500 mg twice daily 4
• Goal dose: 1000-2000 mg daily in divided doses 4
• Titration: Increase by 500 mg daily every 2 weeks until goal dosage is reached 4
• Monitoring: Complete blood count should be monitored during therapy 4
• Common adverse effect: CNS depression 4

CAR T Cell Therapy (Seizure Prophylaxis)

• Dose: 10 mg/kg (maximum 500 mg per dose) every 12 hours for patients with CNS disease or history of seizures 4
• Duration: 30 days following CAR T cell infusion (or through the CRES-risk period) 4
• Generally well-tolerated with minimal risk of drug interactions 4
• Dose adjustments necessary in renal dysfunction 4

Status Epilepticus and Acute Seizures

• Recommended dose: 30 mg/kg IV at a rate of 5 mg/kg per minute for benzodiazepine-resistant status epilepticus 5
• Alternative dosing: 20 mg/kg IV has shown 67% response rate in status epilepticus 5
• Monitor clinical response and EEG after administration 5
• Efficacy comparable to valproate with 73% response rate in benzodiazepine-resistant cases 5

Neurocritical Care (Seizure Prophylaxis)

• Higher doses (>1000 mg total daily dose) are associated with reduced seizure incidence compared to 1000 mg/day in traumatic brain injury and subarachnoid hemorrhage patients 6
• Most commonly used regimen: 1000 mg twice daily (2000 mg total daily dose) 6
• No difference in adverse effects (anemia, leukopenia, thrombocytopenia) between standard and higher dosing 6

Important Pharmacokinetic Considerations

Absorption and Administration

• Oral bioavailability is 100% with rapid absorption 1, 3
• Peak plasma concentration occurs at 1 hour after oral administration in fasted patients 1, 3
• Food decreases Cmax by 20% and delays Tmax by 1.5 hours but does not affect total absorption—can be taken with or without food 1, 3
• Tablets and oral solution are bioequivalent 1

Metabolism and Elimination

• Not metabolized by liver cytochrome P450 enzymes—minimal potential for hepatic drug interactions 1, 3
• 66% excreted unchanged in urine, 24% metabolized by enzymatic hydrolysis of acetamide group 1, 3
• Elimination half-life: 6-8 hours in adults, 5-7 hours in children, 10-11 hours in elderly 3
• Minimal protein binding (<10%)—no significant interactions through protein binding displacement 1, 3

Renal Impairment Dosing

• Dose adjustments are mandatory in moderate to severe renal impairment as clearance is directly dependent on creatinine clearance 1, 3
• Levetiracetam clearance is reduced proportionally to renal function decline 1
• Consult specific renal dosing guidelines based on creatinine clearance 4

Common Adverse Effects

• Most frequent: Somnolence, dizziness, asthenia, headache, and infection 2, 7
• CNS depression is the primary concern across all indications 4, 2, 7
• Overall incidence of adverse events similar to placebo in clinical trials 7
• Adverse events reported in median of 8% of patients receiving levetiracetam versus 21% in comparator groups 8

Drug Interaction Profile

• No clinically relevant interactions with other anticonvulsants, digoxin, warfarin, or oral contraceptives 1, 7, 3
• Does not affect oral contraceptive efficacy 7
• Adverse pharmacodynamic interactions have been demonstrated with carbamazepine and topiramate 3
• Minimal interaction potential makes levetiracetam particularly useful in polypharmacy situations 4, 2

Clinical Efficacy Evidence

• Doses of 1000,2000, and 3000 mg/day significantly increase responder rates and reduce seizure frequency compared to placebo in partial-onset seizures 7
• 3000 mg/day significantly increases seizure-free patients in treatment-refractory partial seizures 7
• Linear pharmacokinetics over 500-5000 mg dose range with no accumulation during multiple dosing 1, 3