Yeni Nesil Bir Antiepiletik İlaç: Levetirasetam

Betül Kalay; Ayper Pekmezekmek; Burçin Ün; Zeki Akarsakarya; Özlem Özü; Ata Seçilmiş

doi:10.17827/aktd.1292345

Review

A New Generatıon Antiepleptic Drug: Levetirasetam

Year 2023, Volume: 32 Issue: 4, 227 - 236, 31.12.2023

Betül Kalay Ayper Pekmezekmek Burçin Ün Zeki Akarsakarya Özlem Özü Ata Seçilmiş

https://doi.org/10.17827/aktd.1292345

Abstract

Pregnant women diagnosed with epilepsy are generally treated with antiepileptic drugs. While many studies have been done with first generation antiepileptic drugs, this number is less for new generation drugs. Although the use of one of these drugs, LEV, in pregnant women is quite common, its effect on the fetus is not fully known. This drug, which is classified as pregnancy category C according to the FDA, is used by performing a benefit-harm analysis since all necessary studies have not been completed.

Keywords

Antiepileptic drugs, Embryo, Epilepsy, Levetiracetam, Pregnancy

References

1. Brunton LL DR, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13 ed. New York: Mac Graw-Hill Education; 2018.
2. Behr C, Goltzene MA, Kosmalski G, Hirsch E, Ryvlin P. Epidemiology of epilepsy. Rev Neurol (Paris). 2016;172:27-36.
3. Hall J, Hall M. Beyin etkinlik durumları – uyku, beyin dalgaları, epilepsi, psikozlar ve demans. In: Yeğen B, ed. Tıbbi Fizyoloji. 14 ed. Ankara: Güneş Tıp Kitabevi; 2021:757-760.
4. Pirkner EH. Epilepsy in the Light of History. Ann Med Hist. 1929;1:453-480.
5. Magiorkinis E, Sidiropoulou K, Diamantis A. Hallmarks in the history of epilepsy: epilepsy in antiquity. Epilepsy Behav. 2010;17:103-108.
6. Von Storch TC. An Essay on the History of Epilepsy. Ann Med Hist. 1930;2:614-650.
7. Rho JM, White HS. Brief history of anti-seizure drug development. Epilepsia Open. 2018;3:114-119.
8. Travers RF. Limbic epilepsy. J R Soc Med. 1991;84:454-456.
9. Rho JM, White HS. Brief history of anti‐seizure drug development. Epilepsia open. 2018;3:114-119.
10. Mula M, Trimble MR, Sander JW. Are psychiatric adverse events of antiepileptic drugs a unique entity? A study on topiramate and levetiracetam. Epilepsia. 2007;48:2322-2326.
11. Günbey C, Turanli G. Epilepsi ve Pediatrik Epilepsi Sendromları. Turkish Journal of Pediatric Disease. 2022:1-9.
12. Epilepsilerde Sınıflandırma (Epilepsi Türleri). https://www.cocuknorolojiuzmani.com/epilepsilerde-siniflandirma-epilepsi-turleri/. Accessed 27 September, 2023.
13. Krishna K, Raut AL, Gohel KH, Dave P. Levetiracetam. J Assoc Physicians India. 2011;59:656-658.
14. Lamouret V, Kurth C, Intravooth T, Steinhoff BJ. Is the anticonvulsant activity of levetiracetam dose-dependent? Seizure. 2020;83:197-202.
15. Potschka H, Baltes S, Loscher W. Inhibition of multidrug transporters by verapamil or probenecid does not alter blood-brain barrier penetration of levetiracetam in rats. Epilepsy Res. 2004;58:85-91.
16. Dedeurwaerdere S, Boon P, De Smedt T, Claeys P, Raedt R, Bosman T, et al. Chronic levetiracetam treatment early in life decreases epileptiform events in young GAERS, but does not prevent the expression of spike and wave discharges during adulthood. Seizure. 2005;14:403-411.
17. French J, Kanner AM, Bautista J, Abou-Khalil B, Browne T, Harden CL, et al. Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society. Epilepsia. 2004;45:410-423.
18. Grunewald R. Levetiracetam in the treatment of idiopathic generalized epilepsies. Epilepsia. 2005;46:154-160.
19. Brighina F, Palermo A, Aloisio A, Francolini M, Giglia G, Fierro B. Levetiracetam in the prophylaxis of migraine with aura: a 6-month open-label study. Clin Neuropharmacol. 2006;29:338-342.
20. Yao X, Yang W, Ren Z, Zhang H, Shi D, Li Y, et al. Neuroprotective and Angiogenesis Effects of Levetiracetam Following Ischemic Stroke in Rats. Front Pharmacol. 2021;12:638209.
21. Chhun S, Jullien V, Rey E, Dulac O, Chiron C, Pons G. Population pharmacokinetics of levetiracetam and dosing recommendation in children with epilepsy. Epilepsia. 2009;50:1150-1157.
22. Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther. 2000;85:77-85.
23. Doheny HC, Ratnaraj N, Whittington MA, Jefferys JG, Patsalos PN. Blood and cerebrospinal fluid pharmacokinetics of the novel anticonvulsant levetiracetam (ucb L059) in the rat. Epilepsy Res. 1999;34:161-168.
24. Tong X, Patsalos PN. A microdialysis study of the novel antiepileptic drug levetiracetam: extracellular pharmacokinetics and effect on taurine in rat brain. Br J Pharmacol. 2001;133:867-874.
25. Trinka E. What is the evidence to use new intravenous AEDs in status epilepticus? Epilepsia. 2011;52 Suppl 8:35-38.
26. Reisinger TL, Newman M, Loring DW, Pennell PB, Meador KJ. Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav. 2013;29:13-18.
27. Leo A, Caro C, Nesci V, Palma E, Tallarico M, Iannone M, et al. Antiepileptogenic effects of Ethosuximide and Levetiracetam in WAG/Rij rats are only temporary. Pharmacol Rep. 2019;71:833-838.
28. Manthey D, Asimiadou S, Stefovska V, Kaindl AM, Fassbender J, Ikonomidou C, et al. Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain. Exp Neurol. 2005;193:497-503.
29. Buyukgol H, Gunes M. The Effects of Antiepileptic Medications on Lipid Profile, Thyroid Panel, and Vitamin Level. Cureus. 2020;12:e11005.
30. 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;48:2111-2115.
31. Karacabey B, Pembegül Yıldız E, M Ç. Antiepileptic Drugs in Children. Journal of Child. 2022;22:117-123.
32. Asadi-Pooya AA, Forouzesh M, Eidi H, Mirzaghafour SE. Levetiracetam versus carbamazepine in treatment of rolandic epilepsy. Epilepsy Behav. 2019;94:1-8.
33. Khurana DS, Kothare SV, Valencia I, Melvin JJ, Legido A. Levetiracetam monotherapy in children with epilepsy. Pediatr Neurol. 2007;36:227-230.
34. Muramatsu K, Sawaura N, Ogata T, Makioka N, Tomita K, Motojima T, et al. Efficacy and tolerability of levetiracetam for pediatric refractory epilepsy. Brain Dev. 2017;39:231-235.
35. Incecik F, Hergüner MO, Altunbasak S. The efficacy and side effects of levetiracetam on refractory epilepsy in children. Journal of pediatric neurosciences. 2012;7:19.
36. Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with use of antiepileptic drugs. Epilepsia. 2004;45:1330-1337.
37. Xiong N, Hou L, Lu N, Mohamed AA, Wang T, Huang Y. Probable levetiracetam-related serum alkaline phosphatase elevation. BMC Neurol. 2012;12:97.
38. El-Haggar SM, Mostafa TM, Allah HMS, Akef GH. Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients. Arq Neuropsiquiatr. 2018;76:452-458.
39. Vestergaard P. Effects of antiepileptic drugs on bone health and growth potential in children with epilepsy. Paediatr Drugs. 2015;17:141-150.
40. Mohammad HMF, Sami MM, Makary S, Toraih EA, Mohamed AO, El-Ghaiesh SH. Neuroprotective effect of levetiracetam in mouse diabetic retinopathy: Effect on glucose transporter-1 and GAP43 expression. Life Sci. 2019;232:116588.
41. Imai T, Sugiyama T, Iwata S, Nakamura S, Shimazawa M, Hara H. Levetiracetam, an Antiepileptic Drug has Neuroprotective Effects on Intracranial Hemorrhage Injury. Neuroscience. 2020;431:25-33.
42. Pinckaers FME, Boon ME, Majoie M. Risk factors predisposing to psychotic symptoms during levetiracetam therapy: A retrospective study. Epilepsy Behav. 2019;100:106344.
43. Erdoğan S, Aslan S, Yüksel N. Levetirasetam Kullanımı ile İlişkili Psikotik Bozukluk: İki Olgu Sunumu. Bulletin of Clinical Psychopharmacology. 2009;19:420.
44. Hurwitz KA, Ingulli EG, Krous HF. Levetiracetam induced interstitial nephritis and renal failure. Pediatr Neurol. 2009;41:57-58.
45. Muller Kuppers M. Embryopathy during pregnancy caused by taking anticonvulsants. Acta Paedopsychiatr. 1963.
46. O'Brien MD, Gilmour-White S. Epilepsy and pregnancy. BMJ. 1993;307:492-495.
47. Karakoç H, Bay F. Gebelikte Epileptik Hastalıklar ve Yönetimi. 2022.
48. Aslan K, Bozdemir H, Unsal C, Guvenc B. The effect of antiepileptic drugs on vitamin B12 metabolism. Int J Lab Hematol. 2008;30:26-35.
49. Meador K, Reynolds MW, Crean S, Fahrbach K, Probst C. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res. 2008;81:1-13.
50. Martinez CS, Feas DA, Siri M, Igartua DE, Chiaramoni NS, Del VAS, et al. In vivo study of teratogenic and anticonvulsant effects of antiepileptics drugs in zebrafish embryo and larvae. Neurotoxicol Teratol. 2018;66:17-24.
51. Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennell P, et al. Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disord. 2019;21:497-517.
52. Vajda FJ, O'Brien TJ, Graham J, Lander CM, Eadie MJ. The outcomes of pregnancy in women with untreated epilepsy. Seizure. 2015;24:77-81.
53. Kezban A. Current Views on the Use of Valproic Acid in Women. Journal of the Turkish Epilepsi Society. 2019;25.
54. Temiz C, Temiz P, Demirel A, Sayin M, Umur AS, Ozer FD. Effect of sodium phenytoin concentration on neural tube development in the early stages of chicken embryo development. J Clin Neurosci. 2009;16:307-311.
55. Manford M. Recent advances in epilepsy. J Neurol. 2017;264:1811-1824.
56. Lee SH, Kang JW, Lin T, Lee JE, Jin DI. Teratogenic potential of antiepileptic drugs in the zebrafish model. Biomed Res Int. 2013;2013:726478.
57. Shallcross R, Bromley RL, Irwin B, Bonnett LJ, Morrow J, Baker GA. Child development following in utero exposure. Neurology. 2011:476.
58. Guvenc Y, Dalgic A, Billur D, Karaoglu D, Aydin S, Daglioglu E, et al. The effects of levetiracetam on neural tube development in the early stage of chick embryos. Turk Neurosurg. 2013;23:617-622.
59. Meador KJ, Penovich P, Baker GA, Pennell PB, Bromfield E, Pack A, et al. Antiepileptic drug use in women of childbearing age. Epilepsy Behav. 2009;15:339-343.
60. Ozyurek H, Bozkurt A, Bilge S, Ciftcioglu E, Ilkaya F, Bas DB. Effect of prenatal levetiracetam exposure on motor and cognitive functions of rat offspring. Brain Dev. 2010;32:396-403.
61. Garrity LC, Turner M, Standridge SM. Increased levetiracetam clearance associated with a breakthrough seizure in a pregnant patient receiving once/day extended-release levetiracetam. Pharmacotherapy. 2014;34:e128-132.
62. Kweri CK, Kariuki J, Mwangi A, Kanyoni JM, Macharia P. Evaluation of embryonic teratogenic effects on fetal growth and development following prenatal exposure to different doses of levetiracetam in albino rats (rattus norvegicus). Journal Of Agriculture, Science And Technology. 2023;22:72-82.
63. Blotière P-O, Miranda S, Weill A, Mikaeloff Y, Peyre H, Ramus F, et al. Risk of early neurodevelopmental outcomes associated with prenatal exposure to the antiepileptic drugs most commonly used during pregnancy: a French nationwide population-based cohort study. BMJ open. 2020;10:e034829.
64. Alsfouk BA. Neurodevelopmental outcomes in children exposed prenatally to levetiracetam. Ther Adv Drug Saf. 2022;13:20420986221088419.
65. El-Shorbagy HM, Hamdi H. Genotoxic and mutagenic studies of the antiepileptic drug levetiracetam in pregnant rats and their fetuses. Int J Pharm Sci. 2016;8:82-88.
66. Yen PH, Kuan YC, Tam KW, Chung CC, Hong CT, Huang YH. Efficacy of levetiracetam for migraine prophylaxis: A systematic review and meta-analysis. J Formos Med Assoc. 2021;120:755-764.
67. Sabbah WS, Hanafy SM, Arafa MAA. Biochemical and histological study on the effect of levetiracetam on the liver and kidney of pregnant albino rats. Folia Morphol (Warsz). 2019;78:809-817.
68. Tureci E, Asan Z, Eser M, Tanriverdi T, Alkan F, Erdincler P. The effects of valproic acid and levetiracetam on chicken embryos. J Clin Neurosci. 2011;18:816-820.
69. Bello-Espinosa LE, Roberts SL. Levetiracetam for benign epilepsy of childhood with centrotemporal spikes-three cases. Seizure. 2003;12:157-159.
70. Yaliwal RG, Biradar AM, Bhagavati SB, Kori SS, Mudanur SR. A Randomized Parallel Non-inferiority Trial to Evaluate the Safety and Efficacy of Levetiracetam in Comparison to Magnesium Sulfate in the Management of Severe Preeclampsia. 2022.
71. Kalay B. Epilepsi Tedavisinde Kullanılan Levetirasetamın Xenopus laevis Embriyoları Üzerindeki Teratojenik Etkisi [Master]. University of Çukurova: Medical Pharmacology, University of Çukurova; 2023.