Safety and efficacy of levetiracetam for the treatment of partial onset seizures in children from one month of age

Neuropsychiatric Disease and Treatment

Volumn 9, Issue , 2013, Pages 295-306

  Cormier, Justine ^a   Chu, Catherine J ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Anticonvulsant drug; Levetiracetam; Partial seizures; Pediatric epilepsy

Indexed keywords

ANTICONVULSIVE AGENT; CARBAMAZEPINE; CLOBAZAM; CLONAZEPAM; CORTICOTROPIN; ETIRACETAM; GABAPENTIN; LAMOTRIGINE; OXCARBAZEPINE; PERAMPANEL; PHENOBARBITAL; PLACEBO; PYRIDOXINE; RUFINAMIDE; TOPIRAMATE; VALPROIC ACID; VIGABATRIN;

ACUTE PSYCHOSIS; ADD ON THERAPY; ADJUVANT THERAPY; AGE DISTRIBUTION; AGGRESSION; ALERTNESS; ANOREXIA; ANTICONVULSANT ACTIVITY; ARTICLE; AUTOMUTILATION; BEHAVIOR DISORDER; BENIGN CHILDHOOD EPILEPSY; BENIGN EPILEPSY WITH CENTROTEMPORAL SPIKE; BINDING AFFINITY; CHILD; CHOREOATHETOSIS; CLINICAL TRIAL (TOPIC); COGNITIVE DEFECT; CONCENTRATION LOSS; CONSTIPATION; CONVULSION; DEPRESSION; DIARRHEA; DOSE RESPONSE; DRUG ABSORPTION; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG ERUPTION; DRUG FEVER; DRUG FORMULATION; DRUG INDICATION; DRUG INDUCED HEADACHE; DRUG INHIBITION; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG WITHDRAWAL; EPILEPSY; EPILEPTIC ENCEPHALOPATHY WITH CONTINUOUS SPIKE AND WAVE ACTIVITY; EPILEPTIC STATE; EXTENDED RELEASE FORMULATION; FATIGUE; FOCAL EPILEPSY; FOOD AND DRUG ADMINISTRATION; GENERALIZED EPILEPSY; GINGIVA DISEASE; HAIR LOSS; HALLUCINATION; HEMORRHAGIC COLITIS; HIGH RISK POPULATION; HUMAN; HYPERACTIVITY; HYPERSALIVATION; INFANT; INFANTILE SPASM; INSOMNIA; INTRACTABLE EPILEPSY; IRRITABILITY; LENNOX GASTAUT SYNDROME; LOADING DRUG DOSE; MAJOR DEPRESSION; MENTAL DISEASE; MONOTHERAPY; MOOD CHANGE; NAUSEA; NERVOUSNESS; NONHUMAN; OTITIS MEDIA; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECOMMENDED DRUG DOSE; RHINOPHARYNGITIS; RISK BENEFIT ANALYSIS; SIDE EFFECT; SLEEP DISORDER; SOMNOLENCE; SUICIDAL BEHAVIOR; SUICIDAL IDEATION; TONIC CLONIC SEIZURE; TREATMENT DURATION; TREMOR; TUBEROUS SCLEROSIS; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; VOMITING; WEIGHT CHANGE;

EID: 84874383369     PISSN: 11766328     EISSN: 11782021     Source Type: Journal    
DOI: 10.2147/NDT.S30224     Document Type: Article

References (79)

1. Shinnar S, Pellock JM. Update on the epidemiology and prognosis of pediatric epilepsy. J Child Neurol. 2002;17 Suppl 1:S4-S17.
2. CDC. Targeting epilepsy: Improving the lives of people with one of the nation's most common neurological conditions. 2011. Available from: http://www.cdc.gov/chronicdisease/resources/publications/AAG/epilepsy.htm. Accessed January 23, 2013.
3. Lagae L, Buyse G, Ceulemans B. Clinical experience with levetiracetam in childhood epilepsy: an add-on and mono-therapy trial. Seizure. 2005;14(1):66-71.
4. Opp J, Tuxhorn I, May T, et al. Levetiracetam in children with refractory epilepsy: a multicenter open label study in Germany. Seizure. 2005;14(7): 476-484.
5. Mandelbaum DE, Bunch M, Kugler SL, Venkatasubramanian A, Wollack JB. Efficacy of levetiracetam at 12 months in children classified by seizure type, cognitive status, and previous anticonvulsant drug use. J Child Neurol. 2005;20(7):590-594.
6. Glauser TA, Ayala R, Elterman RD, et al. Double-blind placebo- controlled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology. 2006;66(11):1654-1660.
7. Perry MS, Benatar M. Efficacy and tolerability of levetiracetam in children younger than 4 years: a retrospective review. Epilepsia. 2007;48(6):1123-1127.
8. Perry S, Holt P, Benatar M. Levetiracetam versus carbamazepine monotherapy for partial epilepsy in children less than 16 years of age. J Child Neurol. 2008;23(5):515-519.
9. Callenbach PM, Arts WF, ten Houten R, et al. Add-on levetiracetam in children and adolescents with refractory epilepsy: results of an open-label multi-centre study. Eur J Paediatr Neurol. 2008;12(4): 321-327.
10. Pina-Garza JE, Nordli DR Jr, Rating D, et al. Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures. Epilepsia. 2009;50(5):1141-1149.
11. Schiemann-Delgado J, Yang H, Loge Cde L, et al. A long-term open-label extension study assessing cognition and behavior, tolerability, safety, and efficacy of adjunctive levetiracetam in children aged 4 to 16 years with partial-onset seizures. J Child Neurol. 2012;27(1):80-89.
12. Lynch BA, Lambeng N, Nocka K, et al. The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam. Proc Natl Acad Sci U S A. 2004;101(26):9861-9866.
13. Kaminski RM, Gillard M, Leclercq K, et al. Proepileptic phenotype of SV2A-defcient mice is associated with reduced anticonvulsant efficacy of levetiracetam. Epilepsia. 2009;50(7):1729-1740.
14. Crowder KM, Gunther JM, Jones TA, et al. Abnormal neurotrans- mission in mice lacking synaptic vesicle protein 2A (SV2A). Proc Natl Acad Sci U S A. 1999;96(26):15268-15273.
15. van Vliet EA, Aronica E, Redeker S, Boer K, Gorter JA. Decreased expression of synaptic vesicle protein 2A, the binding site for levetiracetam, during epileptogenesis and chronic epilepsy. Epilepsia. 2009;50(3):422-433.
16. Goraya JS, Khurana DS, Valencia I, et al. Intravenous levetiracetam in children with epilepsy. Pediatr Neurol. 2008;38(3):177-180.
17. Michaelides C, Thibert RL, Shapiro MJ, et al. Tolerability and dosing experience of intravenous levetiracetam in children and infants. Epilepsy Res. 2008;81(2-3):143-147.
18. Grosso S, Franzoni E, Coppola G, et al. Efficacy and safety of levetiracetam: an add-on trial in children with refractory epilepsy. Seizure. 2005;14(4):248-253.
19. Obeid M, Pong AW. Efficacy and tolerability of high oral doses of levetiracetam in children with epilepsy. Epilepsy Res. 2010;91(1): 101-105.
20. Giroux PC, Salas-Prato M, Theoret Y, Carmant L. Levetiracetam in children with refractory epilepsy: lack of correlation between plasma concentration and efficacy. Seizure. 2009;18(8):559-563.
21. Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther. 2000;85(2):77-85.
22. Pellock JM, Glauser TA, Bebin EM, et al. Pharmacokinetic study of levetiracetam in children. Epilepsia. 2001;42(12):1574-1579.
23. Glauser TA, Mitchell WG, Weinstock A, et al. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia. 2007;48(6):1117-1122.
24. Fountain NB, Conry JA, Rodriguez-Leyva I, et al. Prospective assessment of levetiracetam pharmacokinetics during dose escalation in 4- to 12-year-old children with partial-onset seizures on concomitant carbamazepine or valproate. Epilepsy Res. 2007;74(1):60-69.
25. Nicolas JM, Collart P, Gerin B, et al. In vitro evaluation of potential drug interactions with levetiracetam, a new antiepileptic agent. Drug Metab Dispos. 1999;27(2):250-254.
26. Hirsch LJ, Arif H, Buchsbaum R, et al. Effect of age and comedication on levetiracetam pharmacokinetics and tolerability. Epilepsia. 2007; 48(7):1351-1359.
27. Contin M, Albani F, Riva R, Baruzzi A. Levetiracetam therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2004;26(4):375-379.
28. Dahlin MG, Wide K, Ohman I. Age and comedications infuence levetiracetam pharmacokinetics in children. Pediatr Neurol. 2010;43(4): 231-235.
29. Otoul C, De Smedt H, Stockis A. Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy. Epilepsia. 2007;48(11): 2111-2115.
30. Levisohn PM, Mintz M, Hunter SJ, Yang H, Jones J. N01103 Levetiracetam Study Group. Neurocognitive effects of adjunctive levetiracetam in children with partial-onset seizures: A randomized, double-blind, placebo-controlled, noninferiority trial. Epilepsia. 2009; 50(11):2377-2389.
31. Pina-Garza JE, Schiemann-Delgado J, Yang H, Duncan B, Hadac J, Hunter SJ. Adjunctive levetiracetam in patients aged 1 month to,4 years with partial-onset seizures: subpopulation analysis of a prospective, open-label extension study of up to 48 weeks. Clin Ther. 2010;32(11):1935-1950.
32. de la Loge C, Hunter SJ, Schiemann J, Yang H. Assessment of behavioral and emotional functioning using standardized instruments in children and adolescents with partial-onset seizures treated with adjunctive levetiracetam in a randomized, placebo-controlled trial. Epilepsy Behav. 2010;18(3):291-298.
33. Mbizvo GK, Dixon P, Hutton JL, Marson AG. Levetiracetam add-on for drug-resistant focal epilepsy: an updated Cochrane Review. Cochrane Database Syst Rev. 2012;9:CD001901.
34. Glauser TA, Pellock JM, Bebin EM, et al. Efficacy and safety of levetiracetam in children with partial seizures: an open-label trial. Epilepsia. 2002;43(5):518-524.
35. Grosso S, Cordelli DM, Franzoni E, et al. Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy. Seizure. 2007;16(4):345-350.
36. Chhun S, Troude P, Villeneuve N, et al. A prospective open-labeled trial with levetiracetam in pediatric epilepsy syndromes: continuous spikes and waves during sleep is defnitely a target. Seizure. 2011;20(4): 320-325.
37. Tan MJ, Appleton RE. Efficacy and tolerability of levetiracetam in children aged 10 years and younger: a clinical experience. Seizure. 2004;13(3):142-145.
38. Wheless J W, Ng YT. Levetiracetam in refractory pediatric epilepsy. J Child Neurol. 2002;17(6):413-415.
39. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs II: treatment of refractory epilepsy: Report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2004;62(8):1261-1273.
40. Verdru P. Epilepsy in children: the evidence for new antiepileptic drugs. Acta Neurol Scand Suppl. 2005;181:17-20.
41. Cilio MR, Bianchi R, Balestri M, et al. Intravenous levetiracetam terminates refractory status epilepticus in two patients with migrating partial seizures in infancy. Epilepsy Res. 2009;86(1):66-71.
42. Kirmani BF, Crisp ED, Kayani S, Rajab H. Role of intravenous levetiracetam in acute seizure management of children. Pediatr Neurol. 2009;41(1):37-39.
43. McTague A, Kneen R, Kumar R, Spinty S, Appleton R. Intravenous levetiracetam in acute repetitive seizures and status epilepticus in children: experience from a children's hospital. Seizure. 2012;21(7): 529-534.
44. Ben-Menachem E, Falter U. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia. 2000;41(10):1276-1283.
45. Alsaadi TM, Shatzel A, Marquez AV, Jorgensen J, Farias S. Clinical experience of levetiracetam monotherapy for adults with epilepsy: 1-year follow-up study. Seizure. 2005;14(2):139-142.
46. Khurana DS, Kothare S V, Valencia I, Melvin JJ, Legido A. Levetiracetam monotherapy in children with epilepsy. Pediatr Neurol. 2007;36(4):227-230.
47. Glauser TA, Cnaan A, Shinnar S, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010; 362(9):790-799.
48. Duchowny M, Pellock JM, Graf WD, et al. A placebo-controlled trial of lamotrigine add-on therapy for partial seizures in children. Lamictal Pediatric Partial Seizure Study Group. Neurology. 1999;53(8): 1724-1731.
49. Camposano SE, Major P, Halpern E, Thiele EA. Vigabatrin in the treatment of childhood epilepsy: a retrospective chart review of efficacy and safety profile. Epilepsia. 2008;49(7):1186-1191.
50. Bouma PA, Bovenkerk AC, Westendorp RG, Brouwer OF. The course of benign partial epilepsy of childhood with centrotemporal spikes: a meta-analysis. Neurology. 1997;48(2):430-437.
51. Coppola G, Franzoni E, Verrotti A, et al. Levetiracetam or oxcarbazepine as monotherapy in newly diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS): an open-label, parallel group trial. Brain Dev. 2007;29(5):281-284.
52. Croona C, Kihlgren M, Lundberg S, Eeg-Olofsson O, Eeg-Olofsson KE. Neuropsychological findings in children with benign childhood epilepsy with centrotemporal spikes. Dev Med Child Neuro l. 1999;41(12):813-818.
53. Giordani B, Caveney AF, Laughrin D, et al. Cognition and behavior in children with benign epilepsy with centrotemporal spikes (BECTS). Epilepsy Res. 2006;70(1):89-94.
54. Weglage J, Demsky A, Pietsch M, Kurlemann G. Neuropsychological, intellectual, and behavioral fndings in patients with centrotemporal spikes with and without seizures. Dev Med Child Neurol. 1997;39(10): 646-651.
55. Chu-Shore CJ, Major P, Camposano S, Muzykewicz D, Thiele EA. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010;51(7):1236-1241.
56. Collins JJ, Tudor C, Leonard JM, Chuck G, Franz DN. Levetiracetam as adjunctive antiepileptic therapy for patients with tuberous sclerosis complex: a retrospective open-label trial. J Child Neurol. 2006;21(1): 53-57.
57. Veggiotti P, Beccaria F, Guerrini R, Capovilla G, Lanzi G. Continuous spike-and-wave activity during slow-wave sleep: syndrome or EEG pattern? Epilepsia. 1999;40(11):1593-1601.
58. International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1989;30(4):389-399.
59. Wang SB, Weng WC, Fan PC, Lee WT. Levetiracetam in continuous spike waves during slow-wave sleep syndrome. Pediatr Neurol. 2008; 39(2):85-90.
60. Capovilla G, Beccaria F, Cagdas S, Montagnini A, Segala R, Paganelli D. Efficacy of levetiracetam in pharmacoresistant continuous spikes and waves during slow sleep. Acta Neurol Scand. 2004;110(3): 144-147.
61. Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur J Paediatr Neurol. 2011;15(1):1-7.
62. Furwentsches A, Bussmann C, Ramantani G, et al. Levetiracetam in the treatment of neonatal seizures: a pilot study. Seizure. 2010;19(3): 185-189.
63. Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol. 2011;44(4):265-269.
64. Abend NS, Gutierrez-Colina AM, Monk HM, Dlugos DJ, Clancy RR. Levetiracetam for treatment of neonatal seizures. J Child Neurol. 2011;26(4):465-470.
65. Bittigau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann N Y Acad Sci. 2003;993:103-114.
66. Manthey D, Asimiadou S, Stefovska V, et al. Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain. Exp Neurol. 2005;193(2):497-503.
67. Kim J, Kondratyev A, Gale K. Antiepileptic drug-induced neuronal cell death in the immature brain: effects of carbamazepine, topiramate, and levetiracetam as monotherapy versus polytherapy. J Pharmacol Exp Ther. 2007;323(1):165-173.
68. Forcelli PA, Janssen MJ, Vicini S, Gale K. Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Ann Neurol. 2012;72(3):363-372.
69. Kossoff EH, Bergey GK, Freeman JM, Vining E P. Levetiracetam psychosis in children with epilepsy. Epilepsia. 2001;42(12): 1611-1613.
70. Youroukos S, Lazopoulou D, Michelakou D, Karagianni J. Acute psychosis associated with levetiracetam. Epileptic Disord. 2003;5(2): 117-119.
71. Tamarelle C, Pandit F, Mazarati A, Riquet A, Vallee L, Auvin S. Levetiracetam-induced depression in a 5-year-old child with partial epilepsy. Seizure. 2009;18(3):235-236.
72. Mula M, Kanner AM, Schmitz B, Schachter S. Antiepileptic drugs and suicidality: an expert consensus statement from the Task Force on Therapeutic strategies of the ILAE Commission on Neuropsychobiology. Epilepsia. September 20, 2012. [Epub ahead of print.]
73. Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study. Lancet Neurol. 2007;6(8):693-698.
74. World Health Organization. Preventing Suicide: A Resource for Primary Health Care Workers. Geneva, Switzerland: World Health Organization; 2000.
75. Vaisleib II, Neft RA. Rapid dosage titration of levetiracetam in children. Pharmacotherapy. 2008;28(3):393-396.
76. Major P, Greenberg E, Khan A, Thiele EA. Pyridoxine supplementation for the treatment of levetiracetam-induced behavior side effects in children: preliminary results. Epilepsy Behav. 2008;13(3):557-559.
77. Dzhala VI, Talos DM, Sdrulla DA, et al. NKCC1 transporter facilitates seizures in the developing brain. Nat Med. 2005;11(11):1205-1213.
78. Kahle KT, Staley KJ. The bumetanide-sensitive Na-K-2Cl cotransporter NKCC1 as a potential target of a novel mechanism-based treatment strategy for neonatal seizures. Neurosurg Focus. 2008;25(3):E22.
79. US Food and Drug Administration. Drug Research and Children. 2011. Available from: http://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm143565.htm. Accessed January 24, 2013.