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Evaluation of Long-Term Effects of Levetiracetam Monotherapy on Hematological and Liver Function Parameters in Children With Idiopathic Epilepsy

Year 2022, Volume: 16 Issue: 2, 144 - 149, 16.03.2022
https://doi.org/10.12956/tchd.975416

Abstract

Objective: We aimed this study, investigated the changes in pre- and post-treatment hematological parameters, liver and kidney function parameters in children that were diagnosed with epilepsy and initiated on levetiracetam (LEV) therapy. 


Methodology:  The study population consisted of 114 children (6-18 years) had normal growth percentiles, that were treated for new-onset epilepsy with LEV monotherapy. In each patient, hematological parameters, B12, ferritin, liver and kidney function parameters were measured before and one/three years after the initiation of the therapy.


Results: The hemoglobin (Hgb) and hematocrit (Htc) levels showed a significant increase and the absolute lymphocyte count (ALC), absolute neutrophil count (ANC) (p=0.000), monocyte percentage (p=0.032), and mean platelet volume (MPV) (p=0.000) levelsshowed a significant decrease. The ALC levels decreased significantly in 6 (5.3%) children. The mean drug dose at three years of treatment was 30.0±5.6 mg/kg/day. No significant difference was found between pre- and post-treatment platelet (PLT) counts and no significant correlation was found between gender and hematological parameters (p>0.05 for both).


Conclusion: Although LEV monotherapy led to changes in the hematological parameters of the epilepsy patients, no significant change was observed in liver function. We suggest that when evaluating the hematological parameters in children with epilepsy, the community’s predisposition should be considered and also children should be examined for iron deficiency and vitamin B12 deficiency anemia before initiating the LEV therapy. It was also revealed that long-term LEV monotherapy is a safe treatment in children with epilepsy.

References

  • Referans 1. Kaeberle J. Epilepsy Disorders and Treatment Modalities. NASNSch Nurse. 2018; 33: 342-344
  • Referans 2. Tekgul H, Gencpinar P, Cavusoglu D, Dundar Olgac N. The efficacy, tolerability and safety of levetiracetam therapy in a pediatric population. Seizure 2016 ;36: 16–21
  • Referans 3. Briggs DE, French JA. Levetiracetam safety profiles and tolerability in epilepsy patients. Expert Opin Drug Saf. 2004; 3: 415-24.
  • Referans 4. 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.
  • Referans 5. Attilakos A, Dinopoulos A, Paschalidou M, Tsirouda M , Karalexi M, Prasouli A, Garoufi A. Long-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: A prospective study. Epilepsy Res. 2018; 145: 160-162.
  • Referans 6. Dinopoulos A, Attilakos A, Paschalidou M, Tsirouda M, Garoufi A, Moustaki M, Siafakas N, Papaevangelou V. Short-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: a prospective study. Epilepsy Res. 2014; 108: 820-3.
  • Referans 7. Behrman Richard E., Kliegman Robert M., Jenson Hal B. (2003). Nelson textbook of pediatrics. 17 th ed. Elsevier, Philadelphia, p:2393-420
  • Referans 8. Çoban S, YılmazKeskin E, İğde M. Association between Maternal and Infantile Markers of Cobalamin Status during the First Month Post-Delivery. Indian J Pediatr 2018; 85: 517-522.
  • Referans 9. Moy RJ. Prevalence, consequences and prevention of childhood nutritional iron deficiency: A child public health perspective. Clin Lab Haematol. 2006; 28: 291–8.
  • Referans 10. Bauer J, Ben-Menachem E, Krämer G, Fryze W, Da Silva S, Kasteleijn-Nolst Trenité DG Levetiracetam: a long-term follow-up study of efficacy and safety. ActaNeurol Scand. 2006; 114: 169-76
  • Referans 11. Aydoğan H, Yalçn S, Karahan MA, BüyükfratE.Pancytopenia associated with levetiracetam treatment in Lafora's disease.Blood Coagul Fibrinolysis. 2012;23(2):175
  • Referans12. Ozdemir H, Sumer S, Karabagli H, Akdemir G, Caliskaner AZ, Artac H. B cell aplasia and hypogammaglobulinemia associated with levetiracetam. Ann Saudi Med. 2018; 38: 65-68
  • Referans13. Fagan A, Fuld J, Soon E. Levetiracetam-induced eosinophilic pneumonia. BMJ Case Rep. 2017: 23; 22
  • Referans14. Bachmann T, Bertheussen K H, Svalheim S, Rauchenzauner M, Luef G, Gjerstad L, Tauboll E. Haematological Side Effects of Antiepileptic Drug Treatment in Patients With Epilepsy. Acta Neurol Scand Supp. 2011; 191: 23-7.
  • Referans15. Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs 2011; 71: 489-514.
  • Referans16. Grosso S, Cordelli DM, Franzoni E, Coppola G, Capovilla G, Zamponi N, et al. Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy. Seizure. 2007; 16 :345-50.
  • Referans17. Vidaurre J, Gedela S, Yarosz S. Antiepileptic Drugs and Liver Disease. Pediatr Neurol. 2017 Dec;77:23-36
  • Referans18. Sethi NK, Sethi PK, Torgovnick J, Arsura E, Cukierwar F. Asymptomatic elevation of liver enzymes due to levetiracetam: a case report. Drug Metabol Drug Interact 2013; 28: 123-124.
  • Referans 19. Broli M, Provini F, Naldi I, Bisulli F, Sama C, Baruzzi A, et al. Unexpected gamma glutamyltransferase rise increase during levetiracetam monotherapy. Epileptic Disord 2010; 12: 81-82.
  • Referans 20. Tan TC, de Boer BW, Mitchell A, Delriviere L, Adams LA, Jeffrey GP, et al. Levetiracetam as a possible cause of fulminant liver failure. Neurology. 2008; 71: 685-6.
  • Referans 21. Hurwitz KA, Ingulli EG, Krous HF. Levetiracetam induced interstitial nephritis and renal failure. Pediatr Neurol 2009; 41: 57-8.
  • Referans 22. Nau KM, Divertie GD, Valentino AK, Freeman WD. Safety and efficacy of levetiracetam for critically ill patients with seizures. Neurocrit Care 2009; 11: 34-7.
  • Referans23. Abou-Khalil B. Levetiracetam in the treatment of epilepsy. Neuropsychiatr Dis Treat 2008; 4: 507-23.

Levetirasetam Monoterapisi Alan İdyopatik Epilepsili Çocuklarda Hematolojik ve Karaciğer Fonksiyon Testlerinin Uzun Dönem Etkilerinin Değerlendirilmesi

Year 2022, Volume: 16 Issue: 2, 144 - 149, 16.03.2022
https://doi.org/10.12956/tchd.975416

Abstract

Amaç: Bu çalışmada epilepsi tanısı ile levetirasetam (LEV) tedavisi başlanan çocuklarda tedavi öncesi ve sonrası hematolojik parametreler, karaciğer ve böbrek fonksiyon parametrelerindeki değişiklikler araştırıldı. 

Metodoloji:  Çalışma popülasyonu 6-18 yaş arasında normal büyüme hızına sahip yeni tanı epilepsisi olan, LEV monoterapisi başlanan 114 çocuktan oluşuyordu. Her hastada hematolojik parametreler, B12, ferritin, karaciğer ve böbrek fonksiyon parametreleri, tedavi başlangıcından önce ve bir/üç yıl sonra ölçüldü.


Bulgular:
Hemoglobin (Hgb) ve hematokrit (Htc) seviyelerinde anlamlı artış ve mutlak lenfosit sayısı (ALC), mutlak nötrofil sayısı (ANC)(p=0.000), monosit yüzdesi (p=0.032) ve ortalama trombosit hacmi görüldü. (MPV)(p=0.000) seviyelerinde anlamlı düşüş görüldü. ALC seviyeleri 6 (%5,3) çocukta önemli ölçüde azaldı. Üç yıllık tedavide ortalama ilaç dozu 30.0±5.6 mg/kg/gün idi. Tedavi öncesi ve sonrası trombosit (PLT) sayıları arasında anlamlı bir fark bulunmadı ve cinsiyet ile hematolojik parametreler arasında anlamlı bir ilişki bulunmadı (her ikisi için p>0.05).

Sonuç: LEV monoterapisi epilepsi hastalarının hematolojik parametrelerinde değişikliklere yol açsa da karaciğer fonksiyonlarında anlamlı bir değişiklik gözlenmedi. Epilepsili çocuklarda hematolojik parametreler değerlendirilirken toplumun yatkınlığının göz önünde bulundurulması ve ayrıca LEV tedavisine başlanmadan önce demir eksikliği ve B12 vitamini eksikliği anemisi olan çocukların da muayene edilmesi gerektiğini öneriyoruz. Ayrıca epilepsili çocuklarda uzun süreli LEV monoterapisinin güvenli bir tedavi olduğu ortaya çıktı.

References

  • Referans 1. Kaeberle J. Epilepsy Disorders and Treatment Modalities. NASNSch Nurse. 2018; 33: 342-344
  • Referans 2. Tekgul H, Gencpinar P, Cavusoglu D, Dundar Olgac N. The efficacy, tolerability and safety of levetiracetam therapy in a pediatric population. Seizure 2016 ;36: 16–21
  • Referans 3. Briggs DE, French JA. Levetiracetam safety profiles and tolerability in epilepsy patients. Expert Opin Drug Saf. 2004; 3: 415-24.
  • Referans 4. 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.
  • Referans 5. Attilakos A, Dinopoulos A, Paschalidou M, Tsirouda M , Karalexi M, Prasouli A, Garoufi A. Long-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: A prospective study. Epilepsy Res. 2018; 145: 160-162.
  • Referans 6. Dinopoulos A, Attilakos A, Paschalidou M, Tsirouda M, Garoufi A, Moustaki M, Siafakas N, Papaevangelou V. Short-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: a prospective study. Epilepsy Res. 2014; 108: 820-3.
  • Referans 7. Behrman Richard E., Kliegman Robert M., Jenson Hal B. (2003). Nelson textbook of pediatrics. 17 th ed. Elsevier, Philadelphia, p:2393-420
  • Referans 8. Çoban S, YılmazKeskin E, İğde M. Association between Maternal and Infantile Markers of Cobalamin Status during the First Month Post-Delivery. Indian J Pediatr 2018; 85: 517-522.
  • Referans 9. Moy RJ. Prevalence, consequences and prevention of childhood nutritional iron deficiency: A child public health perspective. Clin Lab Haematol. 2006; 28: 291–8.
  • Referans 10. Bauer J, Ben-Menachem E, Krämer G, Fryze W, Da Silva S, Kasteleijn-Nolst Trenité DG Levetiracetam: a long-term follow-up study of efficacy and safety. ActaNeurol Scand. 2006; 114: 169-76
  • Referans 11. Aydoğan H, Yalçn S, Karahan MA, BüyükfratE.Pancytopenia associated with levetiracetam treatment in Lafora's disease.Blood Coagul Fibrinolysis. 2012;23(2):175
  • Referans12. Ozdemir H, Sumer S, Karabagli H, Akdemir G, Caliskaner AZ, Artac H. B cell aplasia and hypogammaglobulinemia associated with levetiracetam. Ann Saudi Med. 2018; 38: 65-68
  • Referans13. Fagan A, Fuld J, Soon E. Levetiracetam-induced eosinophilic pneumonia. BMJ Case Rep. 2017: 23; 22
  • Referans14. Bachmann T, Bertheussen K H, Svalheim S, Rauchenzauner M, Luef G, Gjerstad L, Tauboll E. Haematological Side Effects of Antiepileptic Drug Treatment in Patients With Epilepsy. Acta Neurol Scand Supp. 2011; 191: 23-7.
  • Referans15. Lyseng-Williamson KA. Levetiracetam: a review of its use in epilepsy. Drugs 2011; 71: 489-514.
  • Referans16. Grosso S, Cordelli DM, Franzoni E, Coppola G, Capovilla G, Zamponi N, et al. Efficacy and safety of levetiracetam in infants and young children with refractory epilepsy. Seizure. 2007; 16 :345-50.
  • Referans17. Vidaurre J, Gedela S, Yarosz S. Antiepileptic Drugs and Liver Disease. Pediatr Neurol. 2017 Dec;77:23-36
  • Referans18. Sethi NK, Sethi PK, Torgovnick J, Arsura E, Cukierwar F. Asymptomatic elevation of liver enzymes due to levetiracetam: a case report. Drug Metabol Drug Interact 2013; 28: 123-124.
  • Referans 19. Broli M, Provini F, Naldi I, Bisulli F, Sama C, Baruzzi A, et al. Unexpected gamma glutamyltransferase rise increase during levetiracetam monotherapy. Epileptic Disord 2010; 12: 81-82.
  • Referans 20. Tan TC, de Boer BW, Mitchell A, Delriviere L, Adams LA, Jeffrey GP, et al. Levetiracetam as a possible cause of fulminant liver failure. Neurology. 2008; 71: 685-6.
  • Referans 21. Hurwitz KA, Ingulli EG, Krous HF. Levetiracetam induced interstitial nephritis and renal failure. Pediatr Neurol 2009; 41: 57-8.
  • Referans 22. Nau KM, Divertie GD, Valentino AK, Freeman WD. Safety and efficacy of levetiracetam for critically ill patients with seizures. Neurocrit Care 2009; 11: 34-7.
  • Referans23. Abou-Khalil B. Levetiracetam in the treatment of epilepsy. Neuropsychiatr Dis Treat 2008; 4: 507-23.
There are 23 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section ORIGINAL ARTICLES
Authors

Beril Dilber 0000-0002-7633-0060

Nihal Yıldız 0000-0003-0989-842X

Hüseyin Yaman 0000-0003-4440-3912

Tulay Kamasak 0000-0002-5212-0149

Gülnur Esenülkü 0000-0002-9423-6078

Pınar Özkan 0000-0001-5726-737X

Elif Acar Arslan 0000-0002-3284-107X

Sevim Şahin 0000-0001-5415-5874

Süleyman Karahan 0000-0001-5091-081X

Ali Cansu 0000-0002-1930-6312

Publication Date March 16, 2022
Submission Date July 28, 2021
Published in Issue Year 2022 Volume: 16 Issue: 2

Cite

Vancouver Dilber B, Yıldız N, Yaman H, Kamasak T, Esenülkü G, Özkan P, Acar Arslan E, Şahin S, Karahan S, Cansu A. Evaluation of Long-Term Effects of Levetiracetam Monotherapy on Hematological and Liver Function Parameters in Children With Idiopathic Epilepsy. Türkiye Çocuk Hast Derg. 2022;16(2):144-9.


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