Brand Name: Keppra
Active Ingredient: levetiracetam
Indication: Adjunctive therapy for patients with partial onset epileptic seizures
Company Name: UCB Pharma, Inc
Availability: Approved for marketing in the US on December 1, 1999
More than 2 million people in the US have some form of epilepsy. Seventy percent of them are adults. Although contemporary treatment approaches can provide full or partial control of seizures in about 85% of patients, some 15% of patients do not achieve this control, and many patients are virtually resistant to available drug therapies. Some patients with partial onset seizures – those that originate in one hemisphere of the brain, often without loss of consciousness – resort to surgery to remove the affected area of the brain, ideally without affecting personality or function.
Now a new drug manufactured by UCB Pharma, Inc. – Keppra (levetiracetam) – may help patients with partial onset epileptic seizures when administered with other antiepileptic drugs (AEDs). Keppra’s approval within ten months of NDA submission to the FDA makes it the fastest AED approval to date. Keppra has several features that make it a valuable antiseizure medication: Clinicians can initiate treatment with an effective 500 mg daily dose, rather than begin with a subtherapeutic dose and titrate upward. Moreover, Keppra displays a favorable safety profile and does not interact with concomitantly administered AEDs or other drugs (such as oral contraceptives, digoxin, warfarin, and probenecid).
Keppra is approved for use in adults and is available in 250 mg, 500 mg, and 750 mg tablets for oral administration with or without food.
Keppra: How It Works
The exact mechanism by which Keppra exerts its antiepileptic effect is not known and does not appear to derive from any interaction with mechanisms known to be involved in inhibitory and excitatory neurotransmission. In vitro studies show that a stereoselective binding site for Keppra exists exclusively in the synaptic plasma membranes of the central nervous system, but not in peripheral tissues. Both in vitro and in vivo recordings of epileptiform activity from the hippocampus show that Keppra inhibits burst firing without affecting normal neuronal excitability. This finding suggests that Keppra may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity.
Keppra: Clinical Study Results
The efficacy of Keppra was demonstrated in three multicenter, randomized, double-blind, placebo-controlled studies in 904 patients with refractory partial onset seizures with or without secondary generalization. At the time of the study, patients were taking a stable dose of 1 to 2 AEDs and were required to have experienced at least four partial onset seizures during each 4-week period during the 12-week baseline period.
Each of the three studies consisted of the 12-week baseline period followed by an 18-week treatment period. The treatment period included a 6-week titration period followed by a 12-week fixed-dose evaluation period, during which concomitant AED regimens were continued. The primary measure of effectiveness was the percent reduction in weekly partial seizure frequency relative to placebo during the entire 18-week treatment period. Responder rate (the incidence of patients with a seizure reduction of 50% or more) was measured as a secondary outcome.
Study 1 was conducted at 41 sites in the US and compared Keppra 1000 mg/day (97 patients), Keppra 3000 mg/day (101 patients), and placebo (95 patients) given in equally divided doses twice daily. The reduction in weekly seizure frequency was 26.1% in the Keppra 1000 mg group and 30.1% in the Keppra 3000 mg group, a significant reduction compared to placebo. Responder rates were 7.4% for placebo, 37.1% for patients who received 1000 mg Keppra, and 39.6% for the 3000 mg Keppra group – a significant difference.
Study 2 was conducted at 62 centers in Europe and compared Keppra 1000 mg/day (106 patients), Keppra 2000 mg/day (105 patients), and placebo (111 patients) given in equally divided doses twice daily. The reduction in weekly seizure frequency was 17.1% in the Keppra 1000 mg group and 21.4% in the Keppra 2000 mg group, a significant reduction compared to placebo. Responder rates were 6.3% for placebo, 20.8% for patients who received 1000 mg Keppra, and 35.2% for the 3000 mg Keppra group – a significant difference between Keppra and placebo and between the two doses of Keppra.
Study 3 was conducted at 47 centers in Europe and compared Keppra 3000 mg/day (180 patients) and placebo (104 patients). The patients who received Keppra experienced a 23.0% reduction in weekly seizure frequency and achieved a 39.4% responder rate (compared to 14.4% in the placebo group).
Keppra: What the Patient Should Know
Adverse effects associated with Keppra include somnolence and fatigue, dizziness, coordination difficulties (ataxia, abnormal gait, or incoordination), and asthenia. Keppra may also be associated with behavioral symptoms, such as agitation, hostility, anxiety, and depression. These effects occurred primarily during the first four weeks of treatment. Because of associated dizziness and somnolence, patients should be advised to avoid driving or operating heavy machinery until they have gauged the effect of Keppra on their performance. Keppra is also substantially excreted by the kidney, so caution should be taken in administering the proper dose to patients with moderate to severe renal impairment and patients undergoing hemodialysis.