Keppra (Levetiracetam)

General Information

In the US, more than 2 million people have epilepsy. Adults make up seventy percent of them. While 85% of individuals can have their seizures fully or partially controlled with modern treatment approaches, 15% of patients are unable to attain this control, and many people are essentially resistant to current pharmacological medications. Some individuals with partial onset seizures-those that start in one hemisphere of the brain and frequently don't cause unconsciousness-turn to brain surgery to remove the damaged region, hopefully leaving the surrounding brain intact in terms of personality and function.

Now, when used with other antiepileptic medications (AEDs), a new medication made by UCB Pharma, Inc. called Keppra (levetiracetam) may benefit people with partial-onset epileptic seizures. Keppra has the quickest AED approval, receiving FDA clearance within 10 months of the drug's NDA application. Keppra is an effective anti-seizure drug due to several features: rather than starting with a subtherapeutic dose and titrating upward, clinicians can start treatment with an effective dose of 500 mg daily. Additionally, Keppra has a good safety record and doesn't interfere with other medications or concurrently administered AEDs (such as probenecid, digoxin, warfarin, and oral contraceptives).

Keppra is licensed for adults and is available in 250 mg, 500 mg, and 750 mg tablets for oral use with or without meals.

Mechanism of Action

Keppra's precise mode of action is unclear. However, it doesn't seem to include any interactions with systems related to excitatory and inhibitory neurotransmission. According to in vitro research, the central nervous system's synaptic plasma membranes are the only locations in which a stereoselective binding site for Keppra is found; peripheral tissues do not have this site. Keppra reduces burst firing from the hippocampal epileptiform activity without altering normal neuronal excitability, as demonstrated by both in vitro and in vivo research. According to this research, Keppra could be able to specifically stop the spread of seizure activity and the hypersynchronization of epileptiform burst firing.

Clinical Study Results

Three multicenter, randomized, double-blind, placebo-controlled trials involving 904 individuals with refractory partial onset seizures-with or without secondary generalization-showed that Keppra was effective. Patients had to have had at least four partial-onset seizures every four weeks for the 12-week baseline period, and they had to be receiving a stable dose of one to two AEDs at the start of the trial.

Twelve weeks were spent on baseline in each of the three investigations, and then participants received treatment for eighteen weeks. Concurrent AED regimens were maintained during the 12-week fixed-dose assessment period that followed the 6-week titration interval. Throughout the whole 18-week treatment period, the main indicator of efficacy was the percentage decrease in the frequency of weekly partial seizures compared to the placebo. As a secondary outcome, the responder rate-the proportion of patients who experienced a 50% or greater reduction in seizures-was assessed.

Study 1 examined the effects of Keppra 1000 mg/day (97 patients), Keppra 3000 mg/day (101 patients), and placebo (95 patients) administered twice daily at equally divided doses at 41 sites across the United States. A noteworthy decrease in weekly seizure frequency was observed in the Keppra 1000 mg group and the Keppra 3000 mg group, with a drop of 26.1% and 30.1%, respectively, compared to the placebo. Responder rates showed a substantial difference: 7.4% for the placebo group, 37.1% for patients receiving 1000 mg of Keppra, and 39.6% for the group receiving 3000 mg of Keppra.

Study 2 compared patients receiving evenly divided dosages of Keppra 1000 mg/day (106 patients), Keppra 2000 mg/day (105 patients), and placebo (111 patients) administered twice daily at 62 facilities throughout Europe. The Keppra 1000 mg group experienced a reduction in weekly seizure frequency of 17.1%, while the Keppra 2000 mg group experienced a substantial drop of 21.4% compared to the placebo group. There was a notable difference between the two doses of Keppra and between Keppra and placebo, with responder rates for the 1000 mg Keppra group being 20.8%, the 3000 mg Keppra group being 35.2%, and the placebo group being 6.3%.

In Study 3, 180 patients received Keppra 3000 mg/day, while 104 received a placebo. The study was carried out at 47 centers across Europe. Patients on Keppra had a 39.4% responder rate (as opposed to 14.4% in the placebo group) and a 23.0% decrease in the frequency of their weekly seizures.

The Patient Should Know

Keppra side effects include asthenia, weariness and drowsiness, dizziness, and problems with coordination (ataxia, irregular gait, or incoordination). Aside from behavioral symptoms, including anger, agitation, anxiety, and depression, Keppra may also be linked to these. The first four weeks of treatment were when these side effects mainly manifested. Patients should be cautioned not to drive or operate heavy machinery until they know how Keppra affects them due to the related dizziness and sleepiness. Patients with moderate to severe renal impairment and those receiving hemodialysis should be given cautious instructions when delivering the recommended dose of Keppra because the medication is also significantly eliminated by the kidney.