The Side Effects of Levetiracetam Monotherapy in Pediatric Epilepsy Patients

Öz

Levetiracetam is a broad-spectrum second-generation anti-seizure drug. Several side effects can be observed during treatment. In this study, we retrospectively evaluated the side effects of levetiracetam monotherapy in the pediatric epilepsy population and investigated potential indicators that could predict these side effects in the pediatric epilepsy population. The study included pediatric epilepsy patients aged 1-17 who were treated with levetiracetam monotherapy. Data collected included age, gender, body weight, blood pressure, duration of levetiracetam use, dosage, seizure semiology, epilepsy type, EEG and MRI findings, hematological and biochemical laboratory results, and observed side effects. Eighty-five patients were included in the study, with 25 (29%) experiencing side effects. Treatment was discontinued in 11 patients due to these effects. The most common side effects were agitation (9%), headache (6%), and fatigue (5%). No significant relationship was found between side effects and gender, body weight, seizure type, levetiracetam dose, treatment duration, EEG results, or MRI findings. However, vitamin B12 levels were lower in patients with side effects compared to those without. Additionally, side effects were more frequently observed in older age groups. Levetiracetam treatment has been linked to both physical and behavioral side effects, which were more commonly observed in older age groups. The most frequently reported side effects were agitation, headache, and fatigue. Additionally, lower B12 levels may contribute to the onset of certain side effects.

Anahtar Kelimeler

• Levetiracetam
• Side-efffects
• B12
• Agitation
• Anti-seizure medication

Pediatrik Epilepsi Hastalarında Levetirasetam Monoterapisinin Yan Etkileri

Öz

Levetiracetam geniş spektrumlu ikinci nesil anti-nöbet ilacıdır. Tedavi sırasında çeşitli yan etkiler görülebilir. Bu çalışmada, pediatrik epilepsi popülasyonunda levetiracetam monoterapisinin yan etkilerini retrospektif olarak değerlendirdik. Çalışmaya levetiracetam monoterapisi ile tedavi edilen 1-17 yaş arası epilepsili hastalar dahil edildi. Yaş, cinsiyet, vücut ağırlığı, kan basıncı, levetiracetam kullanım süresi, doz, semiyoloji, epilepsi tipi, EEG ve MRI bulguları, hemogram ve biyokimyasal laboratuvar bulguları ve gözlenen yan etkiler kaydedildi. Çalışmaya 85 hasta dahil edildi. Yirmi beş (%29) hastada yan etki görüldü. Yan etkiler nedeniyle 11 hastada tedavi kesildi. En sık görülen üç yan etki ajitasyon (8 hasta, %9), baş ağrısı (5 hasta, %5) ve yorgunluktu (3 hasta, %4). Yan etkiler ile cinsiyet, vücut ağırlığı, nöbet tipi, levetirasetam dozu, süresi, EEG ve MRI bulguları arasında ilişki bulunmamıştır. Yan etki görülen grupta B12 vitamini düzeyleri daha düşük bulunmuştur. Yan etkiler daha yaşlı yaş gruplarında daha sık görülmüştür. Levetirasetam tedavisinde fiziksel-davranışsal yan etkiler gözlenmiştir. Yan etki görülen yaş grubu daha yüksekti. En sık görülen üç yan etki ajitasyon, baş ağrısı ve yorgunluk olmuştur. Düşük B12 düzeyleri bazı yan etkilerin başlamasında rol oynayabilir.

Anahtar Kelimeler

• Levetiracetam
• Side-effects
• Agitation
• B12
• Antiseizure medication

Kaynakça

1. 1. Tekgül H, Gencpinar P, Çavuşoğlu D, Dündar NO. The efficacy, tolerability, and safety of levetiracetam therapy in a pediatric population. Seizure.2016;36:16-21. doi:10.1016/j. seizure.2016.01.017
2. 2. French J, Edrich P, Cramer JA. A systematic review of the safety profile of levetiracetam: a new antiepileptic drug. Epilepsy Res. 2001; 47:77-90.
3. 3. Weijenberg A, Brouwer OF, Callenbach PM. Levetiracetam monotherapy in children with epilepsy: a systematic review. CNS Drugs. 2015; 29:371-382.
4. 4. Koukkari MW, Guarino EJ. Retrospective study of the use of levetiracetam in childhood seizure disorders. J Child Neurol. 2004; 19:944-947.
5. 5. Khurana DS, Kothare SV, Valencia I. Levetiracetam monotherapy in children with epilepsy. Pediatr Neurol. 2007; 36:227-230.
6. 6. Lagae L, Buyse G, Ceulemans B. Clinical experience with levetiracetam in childhood epilepsy: an add-on and mono-therapy trial. Seizure. 2005; 14:66-71.
7. 7. Li J, Xiao N, Chen S. Efficacy and tolerability of levetiracetam in children with epilepsy. Brain Dev. 2011; 33:145-151.
8. 8. Kanemoto K, Nishida T, Hasegawa N. Psychiatric Symptoms of Patients With Epilepsy: Characteristics of Psychiatric Adverse Events by Novel Antiepileptic Medications. Brain Nerve. 2023;75(4):375-389. doi:10.11477/MF.1416202343

9. 9. Mula M, Trimble MR, Yuen A, Liu RSN, Sander JWAS. Psychiatric adverse events during levetiracetam therapy. Neurology. 2003;61(5):704-706. doi:10.1212/01. WNL.0000078031.32904.0D
10. 10. Mula M, Hesdorffer DC. Suicidal behavior and antiepileptic drugs in epilepsy: Analysis of the emerging evidence. Drug Health Patient Saf. 2011;3(1):15-20. doi:10.2147/ dhps. s 13070
11. 11. Mbizvo GK, Dixon P, Hutton JL, Marson AG. The adverse effects profile of levetiracetam in epilepsy: a more detailed look. Int J Neurosci. 2014;124(9):627-634. doi:10.3109/00207454.2013.866951
12. 12. Rashid M, Rajan AK, Chhabra M, Kashyap A. Levetiracetam and cutaneous adverse reactions: A systematic review of descriptive studies. Seizure. 2020; 75:101-109. doi:10.1016/j. seizure.2020.01.002
13. 13. French J, Edrich P, Cramer JA. A Systematic Review of the Safety Profile of Levetiracetam: A New Antiepileptic Drug. Epilepsy Res. 2001; 47:77-90.
14. 14. Li G, Nowak M, Bauer S, et al. Levetiracetam but not valproate inhibits the function of CD8+ T lymphocytes. Seizure. 2013;22(6):462-466. doi:10.1016/J. SEIZURE.2013.03.006
15. 15. Azar AE, Ballas ZK. Reversible panhypogammaglobulinemia associated with the antiepileptic agent levetiracetam. Ann Allergy Asthma Immunol. 2008;101(1):108-109. doi:10.1016/S1081-1206(10)60846-0
16. 16. Azar AE, Ballas ZK. Reversible panhypogammaglobulinemia associated with the antiepileptic agent levetiracetam. Ann Allergy Asthma Immunol. 2008;101(1):108-109. doi:10.1016/S1081-1206(10)60846-0
17. 17. Dilber B, Yıldız N, Yaman H, Kamasak T, Esenülkü G, Özkan P, et al. Evaluation of Long-Term Effects of Levetiracetam Monotherapy on Hematological and Liver Function Parameters in Children With Idiopathic Epilepsy. Türkiye Çocuk Hastalıkları Dergisi. 2022;16(2):144-149.
18. 18. Attilakos A, Dinopoulos A, Paschalidou M, et al. Long-term effect of levetiracetam monotherapy on hematological parameters in children with epilepsy: A prospective study. Epilepsy Res. 2018; 145:160-162. doi:10.1016/j. eplepsyres.2018.07.001
19. 19.Dinopoulos A, Attilakos A, Paschalidou M, et al. Short-term effect of levetiracetam monotherapy on hematologicalparameters in children with epilepsy: A prospective study.Epilepsy Res. 2014;108(4):820-823. doi:10.1016/j. eplepsyres.2014.02.006
20. 20.Linnebank M, Moskau S, Semmler A, et al. Antiepileptic drugsinteract with folate and vitamin B12 serum levels. Ann Neurol.2011;69(2):352-359. doi:10.1002/ANA.22229
21. 21.Cahill V, McCorry D, Soryal I, Rajabally YA. Newer anti-epileptic drugs, vitamin status, and neuropathy: A cross-sectional analysis. Rev Neurol (Paris). 2017;173(1-2):62-66. doi:10.1016/J. NEUROL.2016.09.008
22. 22.Sathyan A, Scaria R, Arunachalam P, Ramasamy M,Thekkekkara D, Sivadasan S. Antiepileptic Drugs–Induced Enuresis in Children: An Overview. J Pharm Technol. 2021;37(2):114-119. doi:10.1177/8755122520964047
23. 23.Incecik F, Herguner OM, Besen S, Altunbasak S. Urinary andfecal incontinence during levetiracetam therapy. Ann Indian Acad Neurol. 2015;18(4):479-480. doi:10.4103/0972-2327.165476
24. 24.Mula M, von Oertzen TJ, Cock HR, Yogarajah M, Lozsadi DA, Agrawal N. Fatigue during treatment with antiepilepticdrugs: A levetiracetam-specific adverse event? Epilepsy Behav.2017; 72:17-21. doi:10.1016/j. yebeh.2017.04.030
25. 25.Thelengana A, Shukla G, Srivastava A, et al. Cognitive,behavioral, and sleep-related adverse effects on the introduction of levetiracetam versus oxcarbazepine for epilepsy. EpilepsyRes. 2019;150: 58-65. doi:10.1016/J .EPILEPSYRES.2019.01.004
26. 26.Bell C, Vanderlinden H, Hiersemenzel R, Otoul C, Nutt D,Wilson S. The effects of levetiracetam on objective andsubjective sleep parameters in healthy volunteers and patientswith partial epilepsy. J Sleep Res. 2002;11(3):255-263. doi:10.1046/J.1365-2869.2002.00301.X
27. 27.Yilmaz H. Comparison of motor activity and sleep in patients with complex partial seizures on levetiracetam treatment and agroup of healthy subjects. Behav Neurol. 2007;18(3):165-170.