Keppra: Levetiracetam

Levetiracetam (Keppra) is now approved by FDA as an antiepileptic agent for adjunctive therapy in treatment of primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy.

Key Points

Keppra
Levetiracetam
UCBAntiepileptic agent for adjunctive therapy in treatment of primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy
The mechanism by which levetiracetam exerts its antiepileptic effect is unknown. Studies have suggested that the agent inhibits burst firing without affecting normal neuronal excitability, which may prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity. This agent was previously approved as adjunctive therapy in the treatment of partial onset seizures in patients aged ≥4 years with epilepsy and as adjunctive therapy in the treatment of myoclonic seizures in patients aged ≥12 years with juvenile myoclonic epilepsy. On March 19, 2007, levetiracetam was approved as adjunctive therapy in the treatment of primary generalized tonic-clonic (PGTC) seizures in patients aged ≥6 years with idiopathic generalized epilepsy.

Efficacy. The efficacy of levetiracetam for this indication was evaluated in a multicenter, randomized, double-blind, placebo-controlled study conducted at 50 sites in 8 countries. Patients were eligible for enrollment if they had idiopathic generalized epilepsy (predominately juvenile myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, or epilepsy with grand mal seizures on awakening) with PGTC seizures, if they were taking a stable dose of 1 or 2 antiepileptic drugs, and if they experienced ≥3 PGTC seizures during the 8-week baseline period. Eligible patients (N=164) were randomized to receive either levetiracetam (n=80) or placebo (n=84). Levetiracetam doses were titrated over 4 weeks to a target dose of 3,000 mg/d for adults or 60 mg/kg/d for children; this target dose was then maintained over 20 weeks. Levetiracetam was administered as 2 equally divided doses per day. The primary end point was percent reduction from baseline in weekly PGTC seizure frequency. Patients treated with levetiracetam experienced a statistically significant decrease from baseline in PGTC seizure frequency (77.6% reduction) compared with patients receiving placebo (44.6% reduction). Among patients treated with levetiracetam, 72.2% experienced ≥50% reduction in weekly seizure rates; 45.2% of patients who received placebo experienced ≥50% reduction in weekly seizure rates.

Safety. Levetiracetam treatment has been associated with nonpsychotic behavioral disorders (including abnormal behavior, aggression, conduct disorder, and irritability). Nonpsychotic mood disorders (including anger, apathy, depression, mood alterations, mood swings, negativism, suicidal ideation, and tearfulness) have also been reported in patients treated with levetiracetam. Rarely, patients treated with levetiracetam have exhibited psychotic-like behavior. The most common adverse events associated with levetiracetam treatment for this indication include nasopharyngitis, fatigue, diarrhea, irritability, mood swings, dizziness, headache, influenza, and somnolence.