Epilepsy levetiracetam

Leppik IE. Three new drugs for epilepsy levetiracetam, oxcarbazepine, and zonisamide. J Child Neurol. 2002 f7 SuppI f S53-7. 

Levetiracetam (Keppra) is approved for adjunctive therapy and treatment of partial onset seizures in adults with epilepsy. Levetiracetam is 100% bioavaflable. Once absorbed, it is <10% bound to protein and has a volume of distribution of 1.0 L/kg. Following an oral dose, it reaches maximum... 

Levetiracetam and phenytoin have been retrospectively compared in the prophylaxis of early and late postoperative seizures in 315 patients [182 ]. Levetiracetam (n = 105) was at least as effective as phenytoin ( = 210) and significantly better tolerated. Adverse effects that prompted a change in antiepileptic drug therapy occurred in one patient taking levetiracetam, who had visual hallucinations, compared with 38 patients taking phenytoin (18%). In patients who were followed for at least 1 year and developed epilepsy, levetiracetam also had a higher retention rate. 

Myoclonic Not mentioned Lamotrigine Valproate Valproate Topiramate (children with severe myoclonic epilepsy of infancy) Second-line Clobazam6 Clonazepam Lamotrigine Levetiracetam Piracetam6 Topiramate... 

Somnolence - In controlled trials of patients with epilepsy, 14.8% of levetiracetam-treated patients reported somnolence compared with 8.4% of placebo patients. 

Elderly No overall differences in safety were observed between subjects 65 years of age or older and younger subjects. There were insufficient numbers of elderly subjects in controlled trials of epilepsy to adequately assess the efficacy of levetiracetam in these patients. Because elderly patients are more likely to have decreased renal function, take care in dose selection it may be useful to monitor renal function. 

Adverse reactions most commonly associated with discontinuation or dose reduction of levetiracetam in patients with epilepsy include convulsion and somnolence. 

Cramer (A, Lepplk IE, DeRue K, et. al. Tolerability of levetiracetam in elderly patients with CNS disorders. Epilepsy Res 2003 56 135-145. 

Levetiracetam As adjunctive therapy in treatment of partial onset seizures in adults with epilepsy. 

Specific myoclonic syndromes are usually treated with valproate an intravenous formulation can be used acutely if needed. It is nonsedating and can be dramatically effective. Other patients respond to clonazepam, nitrazepam, or other benzodiazepines, although high doses may be necessary, with accompanying drowsiness. Zonisamide and levetiracetam may be useful. Another specific myoclonic syndrome, juvenile myoclonic epilepsy, can be aggravated by phenytoin or carbamazepine valproate is the drug of choice followed by lamotrigine and topiramate. 

Marson AG et al Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy A systematic review. Epilepsy Res 2001 46 259. 

Potschka, H., S. Baltes, and W. Loscher. 2004. Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats. Epilepsy Res 58 85. 

A 5-year-old girl with refractory epilepsy treated with a ketogenic diet was given levetiracetam 250 mg bd (25 mg/kg/day). She had a history of mild mental retardation and was receiving special education. Two weeks later she started to have visual hallucinations, became agitated, bit relatives, and could not sleep. Levetiracetam was withdrawn and her symptoms resolved within 24 hours and did not recur. 

Kossoff EH, Bergey GK, Freeman JM, Vining EP. Levetiracetam psychosis in children with epilepsy. Epilepsia 2001 42(12) 1611-3. 

Mula M, Trimble MR, Sander JW. Psychiatric adverse events in patients with epilepsy and learning disabilities taking levetiracetam. Seizure 2004 13(l) 55-7. 

Alsaadi TM, Koopmans S, Apperson M, Farias S. Levetiracetam monotherapy for elderly patients with epilepsy. Seizure 2004 13(1) 58-60. 

Ben-Menachem E. Levetiracetam treatment In epilepsy. Expert Opin Pharmacother. 2003 4(ff) 2079-88. 

Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete. Phenobarbital, introduced in 1912, controlled patients resistant to bromides. The next success was the discovery in 1938 of phenytoin (a hydantoin) which is structurally related to the barbiturates. Since then many other drugs have been discovered, but phenytoin still remains a drug of choice in the treatment of major epilepsy. Over the past ten years there has been a dramatic increase in the number of new anticonvulsant drugs (vigabatrin, gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam), but none has been shown to be superior to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). 

The efficacy and tolerability of levetiracetam 1-4 g/day as add-on treatment for refractory epilepsy have been studied in 29 patients with refractory epilepsy (8). The most common adverse events were somnolence and weakness, the frequency and severity of which increased with increasing doses. 

In a pooled analysis of safety data from double-bUnd, placebo-controUed add-on trials of levetiracetam (1-3 g/ day) in adults with refractory partial seizures, adverse events occurring in at least 3% of patients and with at least 3% higher incidence in the active treatment group were tiredness (14 versus 10%), somnolence (15 versus 10%), dizziness (9 versus 4%), and common cold or upper respiratory tract infections (13 versus 7%) (11). The proportions of patients requiring withdrawal of treatment or dosage reduction owing to adverse events were 15% with levetiracetam and 12% with placebo. The efficacy and tolerability of levetiracetam monotherapy in refractory partial seizures have been studied in a double-blind, pla-cebo-controUed study in 286 patients (12). Adverse events that were more common with levetiracetam and that occurred in more than 5% of cases included weakness, infection, and somnolence. Of 181 patients who took levetiracetam, 36 completed the study compared with only 10 of 105 who took placebo. The tolerability and efficacy of levetiracetam, 2 or 4 g/day, as add-on therapy have been studied in 119 patients with refractory epilepsy (13). Somnolence was the most common reason for withdrawal and occurred more often with levetiracetam than placebo, as did weakness. Somnolence was more common with the higher dose, which was not more effective than... 

Four patients with refractory epilepsy taking carbamaze-pine were given added levetiracetam and developed central nervons system effects (ataxia, diplopia, nystagmns) suggestive of carbamazepine toxicity (18). Rednction in the dose of carbamazepine resolved the symptoms in three cases. Carbamazepine and carbamazepine-epoxide blood concentrations were not altered dnring levetiracetam co-medication. Thns, a pharmacodjmamic interaction between carbamazepine and levetiracetam is likely. 

Abou-Khalil B. Levetiracetam—a new therapeutic option for epilepsy. Today s Ther Trends 2000 18 241-54. 

French J, Edrich P, Cramer JA. A systematic review of the safety profile of levetiracetam a new antiepileptic drug. Epilepsy Res 2001 47(l-2) 77-90. 

Grant R, Shorvon SD. Efficacy and tolerability of 1000-4000 mg per day of levetiracetam as add-on therapy in patients with refractory epilepsy. Epilepsy Res 2000 42(2-3) 89-95. 

Krakow K, Walker M, Otoul C, Sander JW. Long-term continuation of levetiracetam in patients with refractory epilepsy. Neurology 2001 56(12) 1772-4. 

Betts T, Waegemans T, Crawford P. A multicentre, double-bUnd, randomized, parallel group study to evaluate the tolerabiUty and efficacy of two oral doses of levetiracetam, 2000 mg daily and 4000 mg daily, without titration in patients with refractory epilepsy. Seizure 2000 9(2) 80-7. 

Sisodiya SM, Sander JW, Patsalos PN. Carbamazepine toxicity during combination therapy with levetiracetam a pharmacodynamic interaction. Epilepsy Res 2002 48(3) 217-19. 

Levy RH, Ragueneau-Majlessi I, Baltes E. Repeated administration of the novel antiepileptic agent levetiracetam does not alter digoxin pharmacokinetics and pharmacodynamics in healthy volunteers. Epilepsy Res 2001 46(2) 93-9. 

Ragueneau-Majlessi I, Levy RH, Meyerhoff C. Lack of effect of repeated administration of levetiracetam on the pharmacodynamic and pharmacokinetic profiles of warfarin. Epilepsy Res 2001 47(l-2) 55-63. 

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