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Русский журнал детской неврологии

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Эффективность и переносимость леветирацетама (препарат Кеппра®) в лечении эпилепсии: обзор литературы

https://doi.org/10.17650/2073-8803-2015-10-2-38-53

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Аннотация

Несмотря на значительные успехи, достигнутые в эпилептологии, у значительной части пациентов (около 30 %) не удается достичь полного контроля над приступами, в связи с чем остается актуальным создание новых антиэпилептических препаратов (АЭП), рациональных комбинаций существующих АЭП с учетом их механизмов действия. Особый интерес представляют препараты с отличным от других АЭП механизмом действия (к таким препаратам относятся леветирацетам, лакосамид, перампанел и др.). Авторы представляют обзор литературы, посвященный одному из новых препаратов – леветирацетаму (Кеппре) – с отличным от других АЭП механизмом действия. Леветирацетам одобрен к применению в инициальной монотерапии парциальной эпилепсии с вторичной генерализацией или без нее у пациентов с 16 лет, в дополнительной терапии парциальных приступов с вторичной генерализацией или без нее у детей с 1 месяца (оральный раствор) и с 6 лет (таблетированная форма), а также c 12 лет в дополнительной терапии миоклонических приступов при юношеской миоклонической эпилепсии и в лечении генерализованных тонико-клонических приступов при идиопатической генерализованной эпилепсии. В обзоре подробно рассматриваются механизм действия, фармакокинетика, данные об эффективности и переносимости леветирацетама в лечении эпилепсии. Полученные результаты исследований позволяют сделать вывод о том, что леветирацетам – хорошо изученный и перспективный препарат для лечения разных форм эпилепсии в моно- и политерапии. 

Об авторах

К. Ю. Мухин
ООО «Институт детской неврологии и эпилепсии им. Святителя Луки»; Россия, 143396, Москва, Троицк, дер. Пучково, ул. Светлая, 6
Россия


О. А. Пылаева
ООО «Институт детской неврологии и эпилепсии им. Святителя Луки»; Россия, 143396, Москва, Троицк, дер. Пучково, ул. Светлая, 6
Россия


Список литературы

1. Воронкова К.В., Петрухин А.С., Пылаева О.А., Холин А.А. Рациональная антиэпилептическая фармакотерапия. М.: Бином, 2008. 192 с. [Voronkova K.V., Petrukhin A.S., Pylaeva O.A., Kholin A.A. Rational antiepileptic drug treatment. Moscow: Binom, 2008. 192 p. (In Russ.)].

2. Воронкова К.В., Пылаева О.А., Федин А.И. Современные принципы лечения фокальных эпилепсий. Эпилепсия 2011;1(4):2–14. [Voronkova K.V., Pylaeva O.A., Fedin A.I. Modern principles of localized epilepsies treatment. Epilepsia = Epilepsy 2011;1(4):2–14. (In Russ.)].

3. Карлов В.А. Эпилепсия у детей и взрослых женщин и мужчин. М.: Медицина, 2010. С. 543–62. [Karlov V.A. Epilepsy in children and adult women and men. Мoscow: Meditsina, 2010. Pp. 543–62. (In Russ.)].

4. Мухин К.Ю., Петрухин А.С., Миронов М.Б. Эпилептические синдромы. Диагностика и терапия (справочное руководство). М.: Системные решения, 2008. 224 с. [Mukhin K.Yu., Petrukhin A.S., Mironov M.B. Epileptic syndromes. Diagnosis and therapy (reference manual). Moscow: Systemnye resheniya, 2008. 224 p. (In Russ.)].

5. Мухин К.Ю., Пилия С.В., Чадаев В.А. и др. Кеппра в лечении эпилепсии: эффективность и переносимость. Журнал неврологии и психиатрии им. С.С. Корсакова 2005;105(1):49–51. [Mukhin K.Yu., Piliya S.V., Chadaev V.A. et al. Keppra in epilepsy treatment: efficacy and tolerability. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry 2005;105(1): 49–51. (In Russ.)].

6. Мухин К.Ю., Тысячина М.Д., Миронов М.Б. и др. Кеппра в монотерапии эпилепсии: электро-клиническая эффективность и переносимость. Русский журнал детской неврологии 2007;2(3):14–23. [Mukhin K.Yu., Tysyachina M.D., Mironov M.B. et al. Keppra in monotherapy of epilepsy: electroclinical efficacy and tolerability. Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology 2007;2(3):14–23. (In Russ.)].

7. Мухин К.Ю., Тысячина М.Д., Петрухин А.С. Леветирацетам в лечении юношеской миоклонической эпилепсии (предварительные результаты). Русский журнал детской неврологии 2009;4(1):3–10. [Mukhin K.Yu., Tysyachina M.D., Petrukhin A.S. Levetiracetam in treatment of juvenile myoclonic epilepsy (preliminary results). Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology 2009;4(1):3–10. (In Russ.)].

8. Мухин К.Ю., Тысячина М.Д., Петрухин А.С. Применение Кеппры в лечении эпилепсии у детей и молодых взрослых. Материалы симпозиума «Леветирацетам в современной эпилептологии». Consilium Medicum (спецвыпуск) 2008. [Mukhin K.Yu., Tysyachina M.D., Petrukhin A.S. Administration of Keppra for epilepsy treatment in children and young adults. Materials of symposium “Levetiracetam in modern epileptology”. Consilium Medicum (special edition) 2008. (In Russ.)].

9. Пылаева О.А., Воронкова К.В., Петрухин А.С. и др. Эпилепсия и синдром дефицита внимания и гиперактивности (обзор литературы). Вестник эпилептологии 2011;1:3–16. [Pylaeva О.A., Voronkova K.V., Petrukhin A.S. et al. Epilepsy and attention deficit hyperactivity disorder (literature review). Vestnik epileptologii = Bulletin of Epileptology 2011;1:3–16. (In Russ.)].

10. Холин А.А., Ильина Е.С. Сочетание эпилепсии с синдромом дефицита внимания и гиперактивности (клинические примеры). Вестник эпилептологии 2011;1:16– 22. [Kholin A.A., Ilyina E.S. Combination of epilepsy and attention deficit hyperactivity disorder (clinical examples). Vestnik epileptologii = Bulletin of Epileptology 2011;1:16–22. (In Russ.)].

11. Холин А.А., Федонюк И.Д., Колпакчи Л.М. и др. Аггравация эпилепсии при терапии леветирацетамом: наблюдение 28 клинических случаев, факторы риска и профилактика. Русский журнал детской неврологии 2014;8(4)–9(1):5–22. [Kholin A.A., Fedonyuk I.D., Kolpakchi L.M. et al. Epilepsy agrravation at therapy with levetiracetam: observation of 28 clinical cases, risk factors and prevention. Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology 2014;8(4)–9(1):5–22. (In Russ.)].

12. Aksoy D., Cevik B., Kurt S. et al. Hypokalemia and hypomagnesaemia related to levetiracetam use. J Clin Neurosci 2014;21(11):1989–90.

13. Atefy R., Tettenborn B. Nonconvulsive status epilepticus on treatment with levetiracetam. Epilepsy Behav 2005;6(4): 613–6.

14. Auvin S., Chhun S., Berquin P. et al. Aggravation of absence seizure related to levetiracetam. Eur J Paediatr Neurol 2011;15(6):508–11.

15. Azar N.J., Aune P. Acute pancreatitis and elevated liver transaminases after rapid titration of oral levetiracetam. J Clin Neurosci 2014;21(6):1053–4.

16. Becerra J.L., Ojeda J., Corredera E., Ruiz Gimenez J. Review of therapeutic options for adjuvant treatment of focal seizures in epilepsy: focus on lacosamide. CNS Drugs 2011;25 Suppl 1:3–16.

17. Belcastro V., Costa C., Galletti F. et al. Levetiracetam monotherapy in Alzheimer patients with late-onset seizures: a prospective observational study. Eur J Neurol 2007;14(10):1176–8.

18. Ben-Menachem E. Levetiracetam: treatment in epilepsy. Expert Opin Pharmacother 2003;4(11):2079–88.

19. Ben-Menachem E. Weight issues for people with epilepsy – a review. Epilepsia 2007; 48 Suppl 9:42–5.

20. Beran R.G., Berkovic S.F., Black A.B. et al. Efficacy and safety of levetiracetam 1000–3000 mg/day in patients with refractory partial-onset seizures: a multicenter, openlabel single-arm study. Epilepsy Res 2005;63(1):1–9.

21. Caraballo R.H., Cersósimo R., De los Santos C. Levetiracetam-induced seizure aggravation associated with continuous spikes and waves during slow sleep in children with refractory epilepsies. Epileptic Disord 2010;12(2):146–50.

22. Chaudhry S.A., Jong G., Koren G. The fetal safety of levetiracetam: a systematic review. Reprod Toxicol 2014;46:40–5.

23. Cho J.W., Lee J.H. Suppression of myoclonus in corticobasal degeneration by levetiracetam. J Mov Disord 2014;7(1): 28–30.

24. Chouinard M.J., Nguyen D.K., Clement J.F. et al. Catatonia induced by levetiracetam. Epilepsy Behav 2006;8(1): 303–7.

25. Cook M., Shorvon S. The pharmacokinetics and clinical therapeutics of antiepileptic drugs. In: Oxford textbook of epilepsy and epileptic seizures. Oxford: Oxford university press, 2013. Pp. 279–89.

26. Coppola G., Mangano S., Tortorella G. et al. Levetiracetam during 1-year follow-up in children, adolescents, and young adults with refractory epilepsy. Epilepsy Res 2004;59(1): 35–42.

27. Coupez R., Straetemans R., Sehgal G. et al. Levetiracetam: relative bioavailability and bioequivalence of a 10 % oral solution (750 mg) and 750-mg tablets. J Clin Pharmacol 2003;43(12):1370–6.

28. Cramer J.A., De Rue K., Devinsky O. et al. A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials. Epilepsy Behav 2003;4(2):124–32.

29. Devinsky O., Elger C. Efficacy of levetiracetam in partial seizures. Epileptic Disord 2003;5 Suppl 1:S27–31.

30. Dinopoulos A., Attilakos A., Paschalidou M. et al. Short-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: a prospective study. Epilepsy Res 2014;108(4):820–3.

31. Eleni K. Dress syndrome induced by levetiracetam. J Eur Acad Dermatol Venereol 2015;29(2):377–8.

32. Elger C.E., Schmidt D. Modern management of epilepsy: а practical approach. Epilepsy Behav 2008;12(4):501–39.

33. Ganeva G., Dimova D., Kuzmanova R., Georgieva A. Efficacy and safety of levetiracetam in the treatment of highly refractory epilepsy. Eur J Neurol 2004;11(Suppl 2):90.

34. Gayatri N.A., Livingston J.H. Aggravation of epilepsy by antiepileptic drugs. Dev Med Child Neurol 2006;48(5):394–8.

35. Gelisse P., Juntas-Morales R., Genton P. et al. Dramatic weight loss with levetiracetam. Epilepsia 2008;49(2):308–15.

36. Giroux P. C., Salas-Prato M., Théorêt Y. et al. Levetiracetam in children with refractory epilepsy: lack of correlation between plasma concentration and efficacy. Seizure 2009;18(8):559–63.

37. Givon L., Porter S., Padmanabhan B. et al. Levetiracetam, seizures, and suicidality. Harv Rev Psychiatry 2011;19:47–55.

38. Glauser T., Ben-Menachem E., Bourgeois B. et al.; ILAE Subcommission on AED Guidelines. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013;54(3):551–63.

39. Glauser T., Ben-Menachem E., Bourgeois B. et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2006;47(7): 1094–120.

40. Glauser T.A., Mitchell W.G., Weinstock A. et al. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia 2007;48(6):1117–22.

41. Glauser T.A., Pellock J.M., Bebin E.M. et al. Efficacy and safety of levetiracetam in children with partial seizures: an open-label trial. Epilepsia 2002;43(5):518–24.

42. Groselj J., Guerrini R., Van Oene J. et al. TOP-INT-51 Investigators' Group. Experience with topiramate monotherapy in elderly patients with recent-onset epilepsy. Acta Neurol Scand 2005;112(3):144–50.

43. Gustafson M.C., Ritter F.J., Frost M.D. et al. Behavioral and emotional effects of levetiracetam in children with intractable epilepsy. Epilepsia 2002;43:58–62.

44. Harden C.L., Meador K.J., Pennell P.B. et al. Management issues for women with epilepsy-focus on pregnancy (an evidencebased review): II: Teratogenesis and perinatal outcomes: Report of the Quality Standards Subcommittee and Therapeutics and Technology Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Epilepsia 2009;50(5): 1237–46.

45. Hoeritzauer I., Mawhinney E., Irwin B. et al. Increased levetiracetam clearance in pregnancy: is seizure frequency affected? Seizure 2012;21(7):559–60.

46. Hu Y., Liao J.X., Chen L. et al. Efficacy and safety of adjunctive levetiracetam in children younger than 4 years with refractory epilepsy. Zhongguo Dang Dai Er Ke Za Zhi 2010;12(4):256–8.

47. Hunt S., Craig J., Russell A. et al. Levetiracetam in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2006;67(10):1876–9.

48. Johannessen Landmark C. Antiepileptic drugs in non-epilepsy disorders: relations between mechanisms of action and clinical efficacy. CNS Drugs 2008;22(1):27–47.

49. Johannessen S.I., Ben-Menachem E. Management of focal-onset seizures an update on drug treatment. Drugs 2006;66(13): 1701–25.

50. Johannessen S.I., Helde G., Brodtkorb E. Levetiracetam in serum and in breastmilk at birth and during lactation. Epilepsia 2005;46(5):775–7.

51. Kanemura H., Sano F., Ohyama T. et al. Effect of levetiracetam on behavioral problems in pervasive developmental disorder children with epilepsy. Eur J Paediatr Neurol 2014;18(4):482–8.

52. Kasteleijn-Nolst Trenité D.G., Marescaux C., Stodieck S. et al. Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam. Epilepsy Res 1996;25(3): 225–30.

53. Kayani S., Sirsi D. The safety and tolerability of newer antiepileptic drugs in children and adolescents. J Cent Nerv Syst Dis 2012;4:51–63.

54. Kelly K., Stephen L.J., Sills G.J., Brodie MJ.. Levetiracetam in patients with a learning disability and refractory epilepsy. Epilepsia 2003;44(Suppl 8):151.

55. Kikuchi T., Kato M., Takahashi N. et al. Epileptic encephalopathy associated with forced normalization after administration of levetiracetam. No To Hattatsu 2013;45(5):375–8.

56. 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):165–73.

57. Kossoff E.H., Bergey G.K., Freeman J.M. et al. Levetiracetam psychosis in children with epilepsy. Epilepsia 2001;42(12):1611–3.

58. Kuba R., Novotna I., Brazdil M. et al. Long-term levetiracetam treatment in patients with epilepsy: 3-year follow up. Acta Neurol Scand 2010;121(2):83–8.

59. Kwan P., Arzimanoglou A., Berg A.T. et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010;51(6):1069–77.

60. Kwan P., Brodie M.J. Early identification of refractory epilepsy. N Engl J Med 2000;342(5):314–9.

61. Kwan P., Brodie M.J. Epilepsy after the first drug fails: substitution or add-on? Seizure 2000;9(7):464–8.

62. Kwan P., Brodie M.J. Refractory epilepsy: mechanisms and solutions. Expert Rev Neurother 2006;6(3):397–406.

63. Levisohn P.M., Mintz M., Hunter S.J. et al. Levetiracetam Study Group. Neurocognitive effects of adjunctive levetiracetam in children with partial-onset seizures: a randomized, double-blind, placebocontrolled, noninferiority trial. Epilepsia 2009;50(11):2377–89.

64. Lyseng-Williamson K.A. Levetiracetam: a review of its use in epilepsy. Drugs 2011;71(4):489–514.

65. Matías-Guíu J., Molins A., Mauri J.A., Villar E. Acceptability and tolerability of levetiracetam oral solution for the treatment of partial-onset seizures: the SOLUCIÓN study. Methods Find Exp Clin Pharmacol 2010;32(7):507–16.

66. Mawhinney E., Craig J., Morrow J. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology 2013;80(4):400–5.

67. Miller G.S. Pyridoxine ameliorates adverse behavioral effects of levetiracetam in children. Epilepsia 2002;43:1.

68. Mula M., Sander J.W. Negative effects of antiepileptic drugs on mood in patients with epilepsy. Drug Saf 2007;30(7): 555–67.

69. Mula M., Trimble M.R., Sander J.W. Psychiatric adverse events in patients with epilepsy and learning disabilities taking levetiracetam. Seizure 2004;13(1): 55–7.

70. Nakken K.O., Eriksson A.S., Lossius R., Johannessen S.I. A paradoxical effect of levetiracetam may be seen in both children and adults with refractory epilepsy. Seizure 2003;12(1):42–6.

71. Neuwirth M., Saracz J., Hegyi M. et al. Experience with levetiracetam in childhood epilepsy. Ideggyogy Sz 2006;59(5–6):179–82.

72. 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):476–84.

73. Panayiotopoulos С.P. A clinical guide to epileptic syndromes and their treatment. Springer, 2010. 654 p.

74. Panayiotopoulos С.P. Principles of therapy in the epilepsies. In: Clinical guide to epileptic syndromes and their treatment. Springer, 2007. Pp. 155–84.

75. Park E.M., Holmes J.A., Reeder-Hayes K.E. Acute mania associated with levetiracetam treatment. Psychosomatics 2014;55(1):98–100.

76. Patsalos P.N. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 2004;43(11):707–24.

77. Peake D., Mordekar S., Gosalakkal J. et al. Retention rate of levetiracetam in children with intractable epilepsy at 1 year. Seizure 2007;16(2):185–9.

78. Pickrell W.O., Lacey A.S., Thomas R.H. et al. Weight change associated with antiepileptic drugs. J Neurol Neurosurg Psychiatry 2013;84(7):796–9.

79. Piña-Garza J.E., Nordli D.R. Jr, Rating D. et al.; Levetiracetam N01009 Study Group. Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures. Epilepsia 2009;50(5):1141–9.

80. Roivainen R., Karvonen M.K., Puumala T. Seizure control in Unverricht-Lundborg disease: a single-centre study. Epileptic Disord 2014;16(2):191–5.

81. Schiemann-Delgado J., Yang H., de la Loge C. 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 Neur 2012;27(1):80–9.

82. Sharpe D.V., Patel A.D., Abou-Khalil B., Fenichel G.M. Levetiracetam monotherapy in juvenile myoclonic epilepsy. Seizure 2008;17(1):64–8.

83. Shorvon S. Handbook of epilepsy treatment. Singapore: Wiley-Blackwell, 2010.

84. Shorvon S. We live in the age of the clinical guideline. Epilepsia 2006;47(7):1091–3.

85. Somerville E.R. Aggravation of partial seizures by antiepileptic drugs: is there evidence from clinical trials? Neurology 2002;59(1):79–83.

86. Specchio N., Balestri M., Striano P. et al. Efficacy of levetiracetam in the treatment of drug-resistant Rett syndrome. Epilepsy Res 2010;88(2–3):112–7.

87. Specchio N., Boero G., Michelucci R. et al. Effects of levetiracetam on EEG abnormalities in juvenile myoclonic epilepsy. Epilepsia 2008;49(4):663–9.

88. Tomson T., Palm R., Källén K. et al. Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period and lactation. Epilepsia 2007;48(6): 1111–6.

89. Tsai J.J., Yen D.J., Hsih M.S. et al. Efficacy and safety of levetiracetam (up to 2000 mg/ day) in Taiwanese patients with refractory partial seizures: a multicenter, randomized, double-blind, placebo-controlled study. Epilepsia 2006;47(1):72–81.

90. Uebachs M., Albus C., Opitz T. et al. Loss of β1 accessory Na+ channel subunits causes failure of carbamazepine, but not of lacosamide, in blocking high-frequency firing via differential effects on persistent Na+ currents. Epilepsia 2012;53(11):1959–67.

91. Ulloa C.M., Towfigh A., Safdieh J. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures. Neuropsychiatr Dis Treat 2009;5:467–76.

92. Vande Griend J.P., Linnebur S.A., Bainbridge J.L. Probable levetiracetamassociated depression in the elderly: two case reports. Am J Geriatr Pharmacother 2009;7(5):281–4.

93. Villanueva V., Lopez-Gomariz E., Lopez-Trigo J. et al. Rational polytherapy with lacosamide in clinical practice: results of a Spanish cohort analysis RELACOVA. Epilepsy Behav 2012;23(3):298–304.

94. Werhahn KJ. Epilepsy in the elderly. Nervenarzt 2012;83(2):201–4.

95. Westin A.A., Reimers A., Helde G. et al. Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure 2008;17(2):192–8.

96. Wheless J.W. Levetiracetam in the treatment of childhood epilepsy. Neuropsychiatr Dis Treat 2007;3(4):409–21.

97. Zhang Y., Zhai Q., Tang Z., Zhuo M. Therapeutic effect of levetiracetam add-on treatment for frontal lobe epilepsy in 105 children. Nan Fang Yi Ke Da Xue Xue Bao 2014;34(3):364–7.

98. Zou X., Hong Z., Zhou D. Hair loss with levetiracetam in five patients with epilepsy. Seizure 2014;23(2):158–60.


Для цитирования:


Мухин К.Ю., Пылаева О.А. Эффективность и переносимость леветирацетама (препарат Кеппра®) в лечении эпилепсии: обзор литературы. Русский журнал детской неврологии. 2015;10(2):38-53. https://doi.org/10.17650/2073-8803-2015-10-2-38-53

For citation:


Mukhin K.Y., Pylaeva O.A. EFFICACY AND TOLERABILITY OF LEVETIRACETAM (KEPPRA®) IN THE TREATMENT OF EPILEPSY: REVIEW OF LITERATURE. Russian Journal of Child Neurology. 2015;10(2):38-53. (In Russ.) https://doi.org/10.17650/2073-8803-2015-10-2-38-53

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