Antiepileptic Drugs in Children

Öz

Antiepileptic drugs (AEDs) lead to seizure freedom in about 70% of all children with epilepsy. Appropriate drug selection is determined by the patient’s age, seizure semiology, epileptic syndrome, and pharmacogenetic approach. The aim of treatment is to prevent seizures by maintaining the effective dose of one or more antiepileptic drugs. In recent years, many new generation AEDs with less side-effect profiles and drug interactions have been used in clinical practice. The clinical uses and side effects of AEDs are different in children than adults. The characteristics of AEDs in the pediatric age group are extremely important in the success of treatment. In this review, many current sources are examined, and the mechanisms of action, pharmacokinetic properties, clinical use and doses, side effects and drug interactions of AEDs that are frequently used in children are discussed.

Anahtar Kelimeler

• Antiepileptic drugs
• children
• epilepsy

Çocuklarda Antiepileptik İlaçlar

Öz

Antiepileptik ilaçlar (AEİ) ile epilepsi tanılı çocukların yaklaşık %70’nde nöbetler kontrol altına alınır. Seçilecek ilaç hastaların yaşı, nöbet semiyolojisi, epileptik sendrom, farmakogenetik yaklaşım ile belirlenir. Tedavide amaç bir veya daha fazla antiepileptik ilacın etkili dozunu muhafaza ederek nöbet oluşumunu önlemektir. Son yıllarda yan etki profili ve ilaç etkileşimi daha az olan birçok yeni nesil AEİ gündeme gelmiş olup bir kısmı klinik pratikte kullanılmaktadır. Çocuklarda, erişkinlere göre AEİ’lerin klinik kullanımları ve yan etkileri farklıdır. AEİ’lerin çocuk yaş grubuna ait özelliklerinin bilinmesi tedavi başarısında son derece önemlidir. Derlememizde çok sayıda güncel kaynak incelenerek çocukluklarda sık kullanılan AEİ’lerin etki mekanizmaları, farmakokinetik özellikleri, klinik kullanım ve dozları, yan etki ve ilaç etkileşimleri ele alınmıştır.

Anahtar Kelimeler

• Antiepileptik ilaçlar
• çocuklar
• epilepsi

Kaynakça

1. 1. Sillanpaa M, Saarinen M, Schmidt D. Clinical conditions of long-term cure in childhood-onset epilepsy: a 45-year follow-up study. Epilepsy Behav 2014;37:49-53. google scholar
2. 2. LaPenna P, Tormoehlen LM. The Pharmacology and Toxicology of Third-Generation Anticonvulsant Drugs. J Med Toxicol 2017;13:329-42. google scholar
3. 3. V. Singh KP, Verma N. Teratogenic potential of third-generation antiepileptic drugs: Current status and research needs. Pharmacol Rep 2019;71:491-502. google scholar
4. 4. Davies JA. Mechanisms of action of antiepileptic drugs. Seizure 1995;4:267-71. google scholar
5. 5. Kobayashi K, Endoh F, Ohmori I, Akiyama T. Action of antiepileptic drugs on neurons. Brain Dev 2020;42:2-5. google scholar
6. 6. Heimann G, Gladtke E. Pharmacokinetics of phenobarbital in childhood. Eur J Clin Pharmacol 1977;12:305-10. google scholar
7. 7. Nicholas SA, Frances EJ, Terrie EI, Joseph JV. Volpe’s Neurology of the Newborn. 6th ed. Elsevier 2018;311-7. google scholar
8. 8. Favie LMA, Groenendaal F, van den Broek MPH, Rademaker CMA, de Haan TR, van Straaten HLM et al. Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia. Neonatology 2019;116:154-162. google scholar

9. 9. Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T et al. Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012;17:3-23. google scholar
10. 10. Arif H, Buchsbaum R, Weintraub D, Koyfman S, Salas-Humara C, Bazil CW. Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology 2007;68:,1701-9. google scholar
11. 11. Abou-Khalil BW. Update on Antiepileptic Drugs 2019. Continuum 2019;25:508-36. google scholar
12. 12. Patsalos PN, St Louis EK. The Epilepsy Prescriber’s Guide to Antiepileptic Drugs. 3rd ed. Cambridge: Cambridge University Press 2018;256-7. google scholar
13. 13. Tolou-Ghamari Z, Zare M, Habibabadi JM, Najafi MR. A quick review of carbamazepine pharmacokinetics in epilepsy from 1953 to 2012. J Res Med Sci 2013;81-5. google scholar
14. 14. Gilman JT. Carbamazepine dosing for pediatric seizure disorders: the highs and lows. DICP 1991;25:1109-12. google scholar
15. 15. Chung W H, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004;428-86. google scholar
16. 16. US Food and Drug Administration. Oxcarbazepine [prescribing information]. 2017. Available from: https://www.accessdata.fda. gov/drugsatfda_docs/label/2017/021014s036lbl.pdf google scholar
17. 17. May TW, Korn-Merker E, Rambeck B. Clinical pharmacokinetics of oxcarbazepine. Clin Pharmacokinet 2003;42:,1023-42. google scholar
18. 18. Bang LM, Goa KL. Spotlight on oxcarbazepine in epilepsy. CNS Drugs 2004;18:57-61. google scholar
19. 19. Kanner AM, Ashman E, Gloss D, Harden C, Bourgeois B, Bautista JF et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2018;91:82-90. google scholar
20. 20. US Food and Drug Administration. Eslicarbazepine acetate [prescribing information]. 2017. Available from: https://www. accessdata.fda.gov/drugsatfda_docs/label/2017/022416s009lbl. pdf google scholar
21. 21. Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Guerreiro C, Kalviainen R et al. Updated ILAE evidence review of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia 2013;54:551-63. google scholar
22. 22. Tolbert D, Larsen FA. Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol 2019;59:7-19. google scholar
23. 23. Canadian Study Group for Childhood Epilepsy. Clobazam has equivalent efficacy to carbamazepine and phenytoin as monotherapy for childhood epilepsy. Epilepsia 1998;39:952-9. google scholar
24. 24. Ng YT, Collins SD. Clobazam. Neurotherapeutics 2007;4:138-44. google scholar
25. 25. Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet 2004;43:707-24. google scholar
26. 26. Nicholas SA, Frances EJ, Terrie EI, Joseph JV. Volpe’s Neurology of the Newborn. 6th ed. Elsevier 2018; 315. google scholar
27. 27. Sourbron J, Chan H, Wammes-van der Heijden EA, Klarenbeek P, Wijnen B, de Haan, et al. Review on the relevance of therapeutic drug monitoring of levetiracetam. Seizure 2018;62:131-5. google scholar
28. 28. Kirmani BF, Crisp ED, Kayani S, Rajab H. Role of intravenous levetiracetam in acute seizure management of children. Pediatr Neurol 2009;41:37-9. google scholar
29. 29. Ng YT, Hastriter EV, Cardenas JF, Khoury EM, Chapman KE. Intravenous levetiracetam in children with seizures: a prospective safety study. Journal of child neurology 2010;25:551-5. google scholar
30. 30. Gillard M, Fuks B, Leclercq K, Matagne A. Binding characteristics of brivaracetam, a selective, high affinity SV2A ligand in rat, mouse and human brain: relationship to anti-convulsant properties. Eur J Pharmacol 2011;664:36-44. google scholar
31. 31. Brandt C, Klein P, Badalamenti V, Gasalla T, Whitesides J. Safety and tolerability of adjunctive brivaracetam in epilepsy: In-depth pooled analysis. Epilepsy Behav 2020;103:106864. google scholar
32. 32. DeVane CL. Pharmacokinetics, drug interactions, and tolerability of valproate. Psychopharmacol Bull 2003;2:25-42. google scholar
33. 33. Belcastro V, D’Egidio C, Striano P, Verrotti A. Metabolic and endocrine effects of valproic acid chronic treatment. Epilepsy Res 2013;08:1-8. google scholar