Levetiracetam: its use in epilepsy Review article
Article Sidebar
Published:
Mar 31, 2013
Keywords:
levetiracetam, epilepsy, new antiepileptic drugs
Main Article Content
Abstract
Levetiracetam is a new generation antiepileptic drug. It was registered in 1999, and introduced in 2000. The mechanism of action is still the subject of hypotheses. It is used both in children and adults, as the monotherapy or combined therapies, in various forms of epileptic seizures.
Article Details
Issue
Section
Articles
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Copyright: © Medical Education sp. z o.o. License allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
1. Lyseng-Williamson KA. Spotting on levetiracetam in epilepsy. CNS Drugs 2011; 25; 901-905.
2. Mazurkiewicz-Bełdzińska M (red). Polski Przegląd Neurologiczny; Via Medica, Gdańsk 2012.
3. Shorwon SD, Lowenthal A, Janz RD, Bielen D, Loiseau P. European Levetiracetam – Study Group. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. Epilepsia 2000; 41: 1179-1186.
4. Stahl SM. Psychopharmacology of anticonvulsants: levetiracetam as asynaptic vesiculoprotein modulator. J Clin Psychiatry 2009; 65: 1162-1163.
5. Meehan AL, Yang X, McAdams BD, Yuan L, Rothman SM. A new mechanism for antiepileptic drug action: vesicular entry may mediate the effects of levetiracetam. J Neuro-physiol 2011; 106: 1227-1239.
6. Fukujama K, Tanahashi S, Nakagawa M et al. Levetiracetam inhibits neurotransmitter release associated with CICR. Neurosci Letters 2012; 518: 69-74.
7. Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs 2011; 71: 489-514.
8. Update on levetiracetam’s mechanism of action: modulation of potassium and calcium channels. Annual Meeting of The American Epilepsy Society, Philadelphia (USA), 30 listopada – 5 grudnia 2001.
9. Surges R, Volynski K, Walker M. Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilepsy revisited. Ther Adv Neurol Disord 2008; 1: 13-24.
10. Stettner M, Dehmel T, Mausberg AK, Kohne A, Rose CR, Kieseier \BC. Levetiracetam exhibits protective properties on rat Schwann cells in vitro. J Peripher Nerv Syst 2011; 16: 250-260.
11. Madeja M, Margineau DG, Gorji A et al. Reduction of voltage-operated potassium currents by levetiracetam; a novel antiepileptic mechanism of action? Neuropharmacology 2003; 45: 661-671.
12. Update on levetiracetam’s mechanism of action: Part I. 56 Annual Meeting of The American Epilepsy Society; Seattle (USA), 6–11 grudnia 2002.
13. Carunchio I, Pieri M, Ciotti MT, Albo F, Zona C. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia 2007; 48: 654-662.
14. Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age. Clin Pharmacokinet 2006; 45: 351-363.
15. Contin M, Mohamed S, Albani F, Baruzzi A. Levetiracetam clinical pharmacokinetics in elderly and very elderly patients with epilepsy. Epilepsy Res 2012; 98: 130-134.
16. French J. Use of levetiracetam in special populations. Epilepsia 2001; 42: 40-43.
17. Patsalos PN. Pharmacokinetic of levetiracetam: toward ideal characteristics. Pharmacol Ther 2000; 85: 77-85.
18. Ben-Manachem E, Falter U, European Levetiracetam Study Group. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double- blind, responder-selected study evaluating monotherapy. Epilepsia 2000; 41: 1276-1283.
19. Cereghino JJ, Biton V, Abou-Khali BL, Dreifuss F, Gauer LJ, Leppik I, The United States Levetiracetam Study Group. Levetiracetam for partial seizures. Results of a double-blind, randomized clinical trial. Neurology 2000; 55: 236-242.
20. Shorvon SD, Lowenthal A, Janz D, Bielen E, Loiseau P, European Levetiracetam Study Group. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures Epilepsia 2000; 41: 1179-1186.
21. Meencke HJ, Buyle S. Assessment of a dose-response relationship of levetiracetam. Eur J Neurol 2006; 13: 942-946.
22. Berkovic SF, Knowlton RC, Leroy RF, Schiemann J, Falter U, Levetiracetam N01057 Study Group. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology 2007; 69: 1751-1760.
23. Noachtar S, Andermann E, Meyvisch P, Levetiracetam Study Group. Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures. Neurology 2008; 70: 607-616.
24. Striano P, Coppola A, Pezzella M, Ciampa C, Specchino N. An open-label trial of levetiracetam in severe myoclonic epilepsy of infancy. Neurology 2007; 69: 250-254.
25. Labate A, Colosimo E, Gambardella A, Leggio U, Ambrosio R, Quattrone A. Levetiracetam in patients with generalized epilepsy and myoclonic seizures: an open label study. Seizure 2006; 15: 214-218.
26. Scheimann-Dalgado 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: 80-89.
27. Lippa C, Rosso A, Heper M et al. Levetiracetam: a practical option for seizure management in elderly patients with cognitive impairment. J Am Alzheimer Dis Other Demen 2010; 25: 149-154.
28. Trinka E, Dobesberger J. New treatment options in status epilepticus: a critical review on intravenous levetiracetam. Ther Adv Neurol Disord 2009; 2: 79-91.
29. Shorvon S, Bulac M, Cross H, Trinka E, Walker M. The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first London Colloquium on status epilepticus. Epilepsia 2008; 49: 1277-1285.
30. Trinka E. What is evidence to use new intra venous AEDs in status epilepticus? Epilepsia 2011; 52: 35-38.
31. Gallentine WB, Hunnicutt AS, Husain AM. Levetiracetam in children with refractory status epilepticus. Epilepsy Behav 2009; 14: 215-218.
32. Aiquabella M, Falip M, Villanueva V et al. Efficacy of intravenous levetiracetam as an add-on treatment in status epilepticus: a multicentric observational study. Seizure 2011; 20: 60-64.
33. Harden CL. Safety profile of levetiracetam. Epilepsia 2001; 42(supl 4): 36-39.
43. Dinkelacker V, Widman G. Aggressive behavior of epilepsy patients in the course of levetiracetam add-on therapy: report of 33 mild to severe cases. Epilepsy Behav 2003; 4: 537-547.
35. Zaccara G, Gangemi PF, Cincotta M. Central nervous system adverse effects of new antiepileptic drugs. A meta-analysis of placebo-controlled studies. Seizure 2008; 17: 405-421.
36. Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs 2011; 71: 489-514.
37. Charakterystyka Produktu Leczniczego. Keppra 052012.
38. Glauser TA, Ayala R, Elterman RD et al. N159 Study Group Double-blind, placebo controlled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology 2006; 66: 1654-1660.
39. Wu XY, Hong Z, Wu X et al. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures. Epilepsia 2009; 50: 398-405.
40. Berkovic SF, Knowlton RC, Leroy RF, Schiemann J, Falter U, Levetiracetam N01057 Study Group. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology 2007; 69: 1751-1760.
41. Meencke HJ, Buyle S. Assessment of a dose-response relationship of levetiracetam. Eur J Neurol 2006; 13: 942-946.
42. Cramer JA, De Rue K, Deinsky O, Edrich P, Trimble MR. A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or anxiety disorders during clinical trials. Epilepsy Behav 2003; 4: 124-132.
43. Kwan P, Arzimanoglou A, Berg AT et al. Definition of drug resistant epilepsy. Epilepsia 2010; 51: 1069-1077.
44. Steinhoff B, Somerville ER, Van Paesschen W. The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy. Epilepsy Res 2007; 76: 6-14.
45. Bodmer M, Monte AA, Kokko J, Yin S. Safety of non-therapeutic levetiracetam ingestions – a poison center based study. Pharmacoepidemiol Drug Saf 2011; 20: 366-369.
46. Uges JWF, Vecht CJ. Levetiracetam. W: Panayiotopoulos CP (red). Atlas of epilepsies. Springer London-Dordrecht-Heidelberg- New York 2010: 1775-1781.
47. Kaufman KR. Monotherapy treatment of bipolar disorder with levetiracetam. Epilepsy Behav 2004; 5: 1017-1020.
48. Toublanc N, Sargentini-Maier ML, Lacroix B, Jacqmin P, Stockis A. Retrospective population pharmacokinetic analysis of levetiracetam in children and adolescents with epilepsy: dosing recommendations. Clin Pharmacokinet 2008; 47: 333-341.
49. Nakken KO, Erikson AS, Loussius R. A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure 2003; 12: 42-46.
50. Glauser TA, Pellock JM, Bebin EM. Efficacy and safety of levetiracetam in children with partial seizures: an open label trial. Epilepsia 2002; 43: 518-524.
51. Wheless JW. Levetiracetam in refractory pediatric epilepsy. J Child Neurol 2002; 17: 413-415.
52. Kossoff EH, Bergey GK, Freeman JM, Vining EP. Levetiracetam psychosis in children with epilepsy. Epilepsia 2001; 42: 1611-1613.
53. Glauser TA. Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients. J Child Neurol 2004; 19(supl 1): 525-538.
54. Merry L, Martim KL, Chen T. Major birth defects after exposure to newer-generation antiepileptic drugs. JAMA 2011; 306: 826.
55. Tomson T, Battino D, Bonizzoni E et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol 2011; 10: 609-617.
56. Vajda FJ. The Australian Pregnancy Register of Anti-epileptic Drugs: 10 years of progress. J Clin Neurosci 2010; 17: 1485-1488.
57. Vajda FJ, Graham J, Roten A, Lander CM, O’Brien TJ, Eadie M. Teratogenicity of the newer antiepileptic drugs – the Australian experience. J Clin Neurosci 2012; 19: 57-59.
58. Nakken KO, Eriksson AS, Lossius R, Johannessen SI. A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure 2003; 12: 42-46.
59. Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia 2007; 48: 1223-1244.
60. Shah RR. Cardiac effects of antiepileptic drugs. W: Panayiotopoulos CP (red). Atlas of epilepsies. Springer; London-Dordracht- Heidelberg-New York 2010: 1479-1486.
61. Perrucca E, Gidal BE, Baltes E. Effects of antiepileptic co-medication on levetiracetam pharmacokinetics: a pooled analysis of data from randomized adjunctive therapy trials. Epilepsy Res 2003; 53: 47-56.
62. Browne TR, Szabo GK, Leppik IE et al. Absence of pharmacokinetic drug interaction of levetiracetam with phenytoin in patients with epilepsy determined new technique. J Clin Pharmacol 2000; 40: 590-595.
63. Otoul C, De Smedt H, Stockis A. Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topitramate, and lamotrigine in children with epilepsy. Epilepsia 2007; 48: 2111-2115.
64. Perrucca E, Bialer M. The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine. Clin Pharmacokinet 1996; 31: 29-46.
65. Freitas-Lima P, Alexandre V Jr, Pereira LR, Peruccia E, Sakamoto AC. Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy. Epilepsy Res 2011; 94: 117-120.
66. Luszczki JJ, Andres MM, Czuczwar P et al. Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotator test in mice. Eur Neuro-psychopharmacol 2005; 15: 609-616.
2. Mazurkiewicz-Bełdzińska M (red). Polski Przegląd Neurologiczny; Via Medica, Gdańsk 2012.
3. Shorwon SD, Lowenthal A, Janz RD, Bielen D, Loiseau P. European Levetiracetam – Study Group. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures. Epilepsia 2000; 41: 1179-1186.
4. Stahl SM. Psychopharmacology of anticonvulsants: levetiracetam as asynaptic vesiculoprotein modulator. J Clin Psychiatry 2009; 65: 1162-1163.
5. Meehan AL, Yang X, McAdams BD, Yuan L, Rothman SM. A new mechanism for antiepileptic drug action: vesicular entry may mediate the effects of levetiracetam. J Neuro-physiol 2011; 106: 1227-1239.
6. Fukujama K, Tanahashi S, Nakagawa M et al. Levetiracetam inhibits neurotransmitter release associated with CICR. Neurosci Letters 2012; 518: 69-74.
7. Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs 2011; 71: 489-514.
8. Update on levetiracetam’s mechanism of action: modulation of potassium and calcium channels. Annual Meeting of The American Epilepsy Society, Philadelphia (USA), 30 listopada – 5 grudnia 2001.
9. Surges R, Volynski K, Walker M. Is levetiracetam different from other antiepileptic drugs? Levetiracetam and its cellular mechanism of action in epilepsy revisited. Ther Adv Neurol Disord 2008; 1: 13-24.
10. Stettner M, Dehmel T, Mausberg AK, Kohne A, Rose CR, Kieseier \BC. Levetiracetam exhibits protective properties on rat Schwann cells in vitro. J Peripher Nerv Syst 2011; 16: 250-260.
11. Madeja M, Margineau DG, Gorji A et al. Reduction of voltage-operated potassium currents by levetiracetam; a novel antiepileptic mechanism of action? Neuropharmacology 2003; 45: 661-671.
12. Update on levetiracetam’s mechanism of action: Part I. 56 Annual Meeting of The American Epilepsy Society; Seattle (USA), 6–11 grudnia 2002.
13. Carunchio I, Pieri M, Ciotti MT, Albo F, Zona C. Modulation of AMPA receptors in cultured cortical neurons induced by the antiepileptic drug levetiracetam. Epilepsia 2007; 48: 654-662.
14. Perucca E. Clinical pharmacokinetics of new-generation antiepileptic drugs at the extremes of age. Clin Pharmacokinet 2006; 45: 351-363.
15. Contin M, Mohamed S, Albani F, Baruzzi A. Levetiracetam clinical pharmacokinetics in elderly and very elderly patients with epilepsy. Epilepsy Res 2012; 98: 130-134.
16. French J. Use of levetiracetam in special populations. Epilepsia 2001; 42: 40-43.
17. Patsalos PN. Pharmacokinetic of levetiracetam: toward ideal characteristics. Pharmacol Ther 2000; 85: 77-85.
18. Ben-Manachem E, Falter U, European Levetiracetam Study Group. Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double- blind, responder-selected study evaluating monotherapy. Epilepsia 2000; 41: 1276-1283.
19. Cereghino JJ, Biton V, Abou-Khali BL, Dreifuss F, Gauer LJ, Leppik I, The United States Levetiracetam Study Group. Levetiracetam for partial seizures. Results of a double-blind, randomized clinical trial. Neurology 2000; 55: 236-242.
20. Shorvon SD, Lowenthal A, Janz D, Bielen E, Loiseau P, European Levetiracetam Study Group. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures Epilepsia 2000; 41: 1179-1186.
21. Meencke HJ, Buyle S. Assessment of a dose-response relationship of levetiracetam. Eur J Neurol 2006; 13: 942-946.
22. Berkovic SF, Knowlton RC, Leroy RF, Schiemann J, Falter U, Levetiracetam N01057 Study Group. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology 2007; 69: 1751-1760.
23. Noachtar S, Andermann E, Meyvisch P, Levetiracetam Study Group. Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures. Neurology 2008; 70: 607-616.
24. Striano P, Coppola A, Pezzella M, Ciampa C, Specchino N. An open-label trial of levetiracetam in severe myoclonic epilepsy of infancy. Neurology 2007; 69: 250-254.
25. Labate A, Colosimo E, Gambardella A, Leggio U, Ambrosio R, Quattrone A. Levetiracetam in patients with generalized epilepsy and myoclonic seizures: an open label study. Seizure 2006; 15: 214-218.
26. Scheimann-Dalgado 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: 80-89.
27. Lippa C, Rosso A, Heper M et al. Levetiracetam: a practical option for seizure management in elderly patients with cognitive impairment. J Am Alzheimer Dis Other Demen 2010; 25: 149-154.
28. Trinka E, Dobesberger J. New treatment options in status epilepticus: a critical review on intravenous levetiracetam. Ther Adv Neurol Disord 2009; 2: 79-91.
29. Shorvon S, Bulac M, Cross H, Trinka E, Walker M. The drug treatment of status epilepticus in Europe: consensus document from a workshop at the first London Colloquium on status epilepticus. Epilepsia 2008; 49: 1277-1285.
30. Trinka E. What is evidence to use new intra venous AEDs in status epilepticus? Epilepsia 2011; 52: 35-38.
31. Gallentine WB, Hunnicutt AS, Husain AM. Levetiracetam in children with refractory status epilepticus. Epilepsy Behav 2009; 14: 215-218.
32. Aiquabella M, Falip M, Villanueva V et al. Efficacy of intravenous levetiracetam as an add-on treatment in status epilepticus: a multicentric observational study. Seizure 2011; 20: 60-64.
33. Harden CL. Safety profile of levetiracetam. Epilepsia 2001; 42(supl 4): 36-39.
43. Dinkelacker V, Widman G. Aggressive behavior of epilepsy patients in the course of levetiracetam add-on therapy: report of 33 mild to severe cases. Epilepsy Behav 2003; 4: 537-547.
35. Zaccara G, Gangemi PF, Cincotta M. Central nervous system adverse effects of new antiepileptic drugs. A meta-analysis of placebo-controlled studies. Seizure 2008; 17: 405-421.
36. Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs 2011; 71: 489-514.
37. Charakterystyka Produktu Leczniczego. Keppra 052012.
38. Glauser TA, Ayala R, Elterman RD et al. N159 Study Group Double-blind, placebo controlled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology 2006; 66: 1654-1660.
39. Wu XY, Hong Z, Wu X et al. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures. Epilepsia 2009; 50: 398-405.
40. Berkovic SF, Knowlton RC, Leroy RF, Schiemann J, Falter U, Levetiracetam N01057 Study Group. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology 2007; 69: 1751-1760.
41. Meencke HJ, Buyle S. Assessment of a dose-response relationship of levetiracetam. Eur J Neurol 2006; 13: 942-946.
42. Cramer JA, De Rue K, Deinsky O, Edrich P, Trimble MR. A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or anxiety disorders during clinical trials. Epilepsy Behav 2003; 4: 124-132.
43. Kwan P, Arzimanoglou A, Berg AT et al. Definition of drug resistant epilepsy. Epilepsia 2010; 51: 1069-1077.
44. Steinhoff B, Somerville ER, Van Paesschen W. The SKATE study: an open-label community-based study of levetiracetam as add-on therapy for adults with uncontrolled partial epilepsy. Epilepsy Res 2007; 76: 6-14.
45. Bodmer M, Monte AA, Kokko J, Yin S. Safety of non-therapeutic levetiracetam ingestions – a poison center based study. Pharmacoepidemiol Drug Saf 2011; 20: 366-369.
46. Uges JWF, Vecht CJ. Levetiracetam. W: Panayiotopoulos CP (red). Atlas of epilepsies. Springer London-Dordrecht-Heidelberg- New York 2010: 1775-1781.
47. Kaufman KR. Monotherapy treatment of bipolar disorder with levetiracetam. Epilepsy Behav 2004; 5: 1017-1020.
48. Toublanc N, Sargentini-Maier ML, Lacroix B, Jacqmin P, Stockis A. Retrospective population pharmacokinetic analysis of levetiracetam in children and adolescents with epilepsy: dosing recommendations. Clin Pharmacokinet 2008; 47: 333-341.
49. Nakken KO, Erikson AS, Loussius R. A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure 2003; 12: 42-46.
50. Glauser TA, Pellock JM, Bebin EM. Efficacy and safety of levetiracetam in children with partial seizures: an open label trial. Epilepsia 2002; 43: 518-524.
51. Wheless JW. Levetiracetam in refractory pediatric epilepsy. J Child Neurol 2002; 17: 413-415.
52. Kossoff EH, Bergey GK, Freeman JM, Vining EP. Levetiracetam psychosis in children with epilepsy. Epilepsia 2001; 42: 1611-1613.
53. Glauser TA. Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients. J Child Neurol 2004; 19(supl 1): 525-538.
54. Merry L, Martim KL, Chen T. Major birth defects after exposure to newer-generation antiepileptic drugs. JAMA 2011; 306: 826.
55. Tomson T, Battino D, Bonizzoni E et al. Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol 2011; 10: 609-617.
56. Vajda FJ. The Australian Pregnancy Register of Anti-epileptic Drugs: 10 years of progress. J Clin Neurosci 2010; 17: 1485-1488.
57. Vajda FJ, Graham J, Roten A, Lander CM, O’Brien TJ, Eadie M. Teratogenicity of the newer antiepileptic drugs – the Australian experience. J Clin Neurosci 2012; 19: 57-59.
58. Nakken KO, Eriksson AS, Lossius R, Johannessen SI. A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure 2003; 12: 42-46.
59. Zaccara G, Franciotta D, Perucca E. Idiosyncratic adverse reactions to antiepileptic drugs. Epilepsia 2007; 48: 1223-1244.
60. Shah RR. Cardiac effects of antiepileptic drugs. W: Panayiotopoulos CP (red). Atlas of epilepsies. Springer; London-Dordracht- Heidelberg-New York 2010: 1479-1486.
61. Perrucca E, Gidal BE, Baltes E. Effects of antiepileptic co-medication on levetiracetam pharmacokinetics: a pooled analysis of data from randomized adjunctive therapy trials. Epilepsy Res 2003; 53: 47-56.
62. Browne TR, Szabo GK, Leppik IE et al. Absence of pharmacokinetic drug interaction of levetiracetam with phenytoin in patients with epilepsy determined new technique. J Clin Pharmacol 2000; 40: 590-595.
63. Otoul C, De Smedt H, Stockis A. Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topitramate, and lamotrigine in children with epilepsy. Epilepsia 2007; 48: 2111-2115.
64. Perrucca E, Bialer M. The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine. Clin Pharmacokinet 1996; 31: 29-46.
65. Freitas-Lima P, Alexandre V Jr, Pereira LR, Peruccia E, Sakamoto AC. Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy. Epilepsy Res 2011; 94: 117-120.
66. Luszczki JJ, Andres MM, Czuczwar P et al. Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotator test in mice. Eur Neuro-psychopharmacol 2005; 15: 609-616.