Comparing the Efficacy and Safety of Levetiracetam Versus Phenytoin for Treating the Acute Phase of Neonatal Seizures
Iranian Journal of Child Neurology,
Vol. 17 No. 1 (2023),
3 January 2023
,
Page 65-71
https://doi.org/10.22037/ijcn.v17i1.36008
Abstract
Objectives
Neonatal seizure is a significant problem in this life course, and its timely and effective treatment is crucial. In this study, we compared the efficacy of levetiracetam versus phenytoin for treating the acute phase of neonatal seizures.
Materials & Methods
In this single-blind case-control study, 60 consecutive children with neonatal seizures referred to the Children’s medical center in Tehran, Iran, in 2018 were studied. Those neonates who had at least 30 minutes of seizure after Phenobarbital treatment were assigned to receive either phenytoin (20 mg/kg) or levetiracetam (initial dose of 40-60 mg/kg) through block randomization. The efficacy and safety of the two drugs were compared between the groups.
Results
The response rate was 83.3% and 86.7% in phenytoin and Levetiracetam groups, respectively, which was not significantly different between groups (P=1.000). Adverse effects were nearly similar between groups (6.7% in the phenytoin group and 3.3% in the Levetiracetam group, P=1.000).
Conclusion
Levetiracetam and phenytoin are both practical and safe for treating
neonatal seizures.
Keywords:
- Neonatal Seizure, Levetiracetam, phenytoin, safety, efficacy
How to Cite
Mohammadi, Mahmoud, kadivar, maliheh, sangsari, razieh, mirnia, kayvan, saeedi, maryam, & adhami, pedah. (2023). Comparing the Efficacy and Safety of Levetiracetam Versus Phenytoin for Treating the Acute Phase of Neonatal Seizures. Iranian Journal of Child Neurology, 17(1), 65–71. https://doi.org/10.22037/ijcn.v17i1.36008
References
References
1. Co JPT, Elia M, Engel Jr J, Guerrini R, Mizrahi EM, Moshé SL, et al. Proposal of an algorithm for diagnosis and treatment of neonatal seizures in developing countries. Epilepsia. 2007;48(6):1158-64.
2. Shellhaas R, Garcia-Prats JA. Etiology and prognosis of neonatal seizures. 2010.
3. Shellhaas RA, Soaita AI, Clancy RR. Sensitivity of amplitude-integrated electroencephalography for neonatal seizure detection. Pediatrics. 2007;120(4):770-7.
4. Scher MS, Aso K, Beggarly ME, Hamid MY, Steppe DA, Painter MJ. Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae. Pediatrics. 1993;91(1):128-34.
5. Lanska MJ, Lanska DJ, Baumann RJ, Kryscio RJ. A population-based study of neonatal seizures in Fayette County, Kentucky. Neurology. 1995;45(4):724-32.
6. Saliba RM. Incidence of clinical neonatal seizures. Epilepsia. 1996;37(5):13.
7. Wang H, Kuo M, Chou M, Hung P, Lin K, Hsieh M, et al. Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy. Archives of disease in childhood. 2005;90(5):512-5.
8. Nicolai J, van Kranen-Mastenbroek VH, Wevers RA, Hurkx WA, Vles JS. Folinic Acid–Responsive Seizures Initially Responsive to Pyridoxine. Pediatric neurology. 2006;34(2):164-7.
9. Basura GJ, Hagland SP, Wiltse AM, Gospe SM. Clinical features and the management of pyridoxine-dependent and pyridoxine-responsive seizures: review of 63 North American cases submitted to a patient registry. European journal of pediatrics. 2009;168(6):697-704.
10. Schmitt B, Baumgartner M, Mills PB, Clayton PT, Jakobs C, Keller E, et al. Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine‐dependent epilepsy and pyridoxine phosphate oxidase deficiency. Developmental Medicine & Child Neurology. 2010;52(7):e133-e42.
11. Bok LA, Halbertsma FJ, Houterman S, Wevers RA, Vreeswijk C, Jakobs C, et al. Long‐term outcome in pyridoxine‐dependent epilepsy. Developmental Medicine & Child Neurology. 2012;54(9):849-54.
12. Stockler S, Plecko B, Gospe Jr SM, Coulter-Mackie M, Connolly M, van Karnebeek C, et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Molecular genetics and metabolism. 2011;104(1-2):48-60.
13. Bourgeois BF, Dodson WE. Phenytoin elimination in newborns. Neurology. 1983;33(2):173-.
14. Dodson WE. Antiepileptic drug utilization in pediatric patients. Epilepsia. 1984;25:S132-S9.
15. Berkovic SF, Knowlton R, Leroy R, Schiemann J, Falter U, Group LNS. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology. 2007;69(18):1751-60.
16. Shoemaker MT, Rotenberg JS. Levetiracetam for the treatment of neonatal seizures. Journal of child neurology. 2007;22(1):95-8.
17. Hmaimess G, Kadhim H, Nassogne M-C, Bonnier C, Van Rijckevorsel K. Levetiracetam in a neonate with malignant migrating partial seizures. Pediatric neurology. 2006;34(1):55-9.
18. Gallentine WB, Hunnicutt AS, Husain AM. Levetiracetam in children with refractory status epilepticus. Epilepsy & Behavior. 2009;14(1):215-8.
19. Silverstein FS, Ferriero DM. Off-label use of antiepileptic drugs for the treatment of neonatal seizures. Pediatric neurology. 2008;39(2):77-9.
20. Cataldi M, Lariccia V, Secondo A, di Renzo G, Annunziato L. The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]I increase induced by ATP and bradykinin in PC12 cells. J Pharmacol Exp Ther. 2005;313(2):720-30.
21. Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatric neurology. 2011;44(4):265-9.
22. Shoemaker MT, Rotenberg JS. Levetiracetam for the treatment of neonatal seizures. Journal of child neurology. 2007;22(1):95-8.
23. Wu XY, Hong Z, Wu X, Wu LW, Wang XF, Zhou D, et al. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures. Epilepsia. 2009;50(3):398-405.
24. Abend NS, Gutierrez-Colina AM, Monk HM, Dlugos DJ, Clancy RR. Levetiracetam for treatment of neonatal seizures. Journal of child neurology. 2011;26(4):465-70.
25. Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur J Paediatr Neurol. 2011;15(1):1-7.
26. Nikkhah K, Harati H, Rezaeitalab F, Khosravi A, Anvari Ardakani S. A comparison of the effects of lamotrigine and levetiracetamand lamotrigine and valproate sodium in patients with epilepsy. medical journal of mashhad university of medical sciences. 2016;59(3):132-8.
27. Venkatesan C, Young S, Schapiro M, Thomas C. Levetiracetam for the Treatment of Seizures in Neonatal Hypoxic Ischemic Encephalopathy. J Child Neurol. 2017;32(2):210-4.
28. Shin JW, Jung YS, Park K, Lee SM, Eun HS, Park MS, et al. Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures. Korean journal of pediatrics. 2017;60(2):50-4.
29. Mollamohammadi M, Amirhoseini ZS, Saadati A, Pirzadeh Z, Hassan Amouzadeh M. Oral Levetiracetam as Add-On Therapy in Refractory Neonatal Seizures. Iranian journal of child neurology. 2018;12(4):103-10.
30. Han JY, Moon CJ, Youn YA, Sung IK, Lee IG. Efficacy of levetiracetam for neonatal seizures in preterm infants. BMC pediatrics. 2018;18(1):131.
1. Co JPT, Elia M, Engel Jr J, Guerrini R, Mizrahi EM, Moshé SL, et al. Proposal of an algorithm for diagnosis and treatment of neonatal seizures in developing countries. Epilepsia. 2007;48(6):1158-64.
2. Shellhaas R, Garcia-Prats JA. Etiology and prognosis of neonatal seizures. 2010.
3. Shellhaas RA, Soaita AI, Clancy RR. Sensitivity of amplitude-integrated electroencephalography for neonatal seizure detection. Pediatrics. 2007;120(4):770-7.
4. Scher MS, Aso K, Beggarly ME, Hamid MY, Steppe DA, Painter MJ. Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae. Pediatrics. 1993;91(1):128-34.
5. Lanska MJ, Lanska DJ, Baumann RJ, Kryscio RJ. A population-based study of neonatal seizures in Fayette County, Kentucky. Neurology. 1995;45(4):724-32.
6. Saliba RM. Incidence of clinical neonatal seizures. Epilepsia. 1996;37(5):13.
7. Wang H, Kuo M, Chou M, Hung P, Lin K, Hsieh M, et al. Pyridoxal phosphate is better than pyridoxine for controlling idiopathic intractable epilepsy. Archives of disease in childhood. 2005;90(5):512-5.
8. Nicolai J, van Kranen-Mastenbroek VH, Wevers RA, Hurkx WA, Vles JS. Folinic Acid–Responsive Seizures Initially Responsive to Pyridoxine. Pediatric neurology. 2006;34(2):164-7.
9. Basura GJ, Hagland SP, Wiltse AM, Gospe SM. Clinical features and the management of pyridoxine-dependent and pyridoxine-responsive seizures: review of 63 North American cases submitted to a patient registry. European journal of pediatrics. 2009;168(6):697-704.
10. Schmitt B, Baumgartner M, Mills PB, Clayton PT, Jakobs C, Keller E, et al. Seizures and paroxysmal events: symptoms pointing to the diagnosis of pyridoxine‐dependent epilepsy and pyridoxine phosphate oxidase deficiency. Developmental Medicine & Child Neurology. 2010;52(7):e133-e42.
11. Bok LA, Halbertsma FJ, Houterman S, Wevers RA, Vreeswijk C, Jakobs C, et al. Long‐term outcome in pyridoxine‐dependent epilepsy. Developmental Medicine & Child Neurology. 2012;54(9):849-54.
12. Stockler S, Plecko B, Gospe Jr SM, Coulter-Mackie M, Connolly M, van Karnebeek C, et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Molecular genetics and metabolism. 2011;104(1-2):48-60.
13. Bourgeois BF, Dodson WE. Phenytoin elimination in newborns. Neurology. 1983;33(2):173-.
14. Dodson WE. Antiepileptic drug utilization in pediatric patients. Epilepsia. 1984;25:S132-S9.
15. Berkovic SF, Knowlton R, Leroy R, Schiemann J, Falter U, Group LNS. Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy. Neurology. 2007;69(18):1751-60.
16. Shoemaker MT, Rotenberg JS. Levetiracetam for the treatment of neonatal seizures. Journal of child neurology. 2007;22(1):95-8.
17. Hmaimess G, Kadhim H, Nassogne M-C, Bonnier C, Van Rijckevorsel K. Levetiracetam in a neonate with malignant migrating partial seizures. Pediatric neurology. 2006;34(1):55-9.
18. Gallentine WB, Hunnicutt AS, Husain AM. Levetiracetam in children with refractory status epilepticus. Epilepsy & Behavior. 2009;14(1):215-8.
19. Silverstein FS, Ferriero DM. Off-label use of antiepileptic drugs for the treatment of neonatal seizures. Pediatric neurology. 2008;39(2):77-9.
20. Cataldi M, Lariccia V, Secondo A, di Renzo G, Annunziato L. The antiepileptic drug levetiracetam decreases the inositol 1,4,5-trisphosphate-dependent [Ca2+]I increase induced by ATP and bradykinin in PC12 cells. J Pharmacol Exp Ther. 2005;313(2):720-30.
21. Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatric neurology. 2011;44(4):265-9.
22. Shoemaker MT, Rotenberg JS. Levetiracetam for the treatment of neonatal seizures. Journal of child neurology. 2007;22(1):95-8.
23. Wu XY, Hong Z, Wu X, Wu LW, Wang XF, Zhou D, et al. Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in Chinese patients with refractory partial-onset seizures. Epilepsia. 2009;50(3):398-405.
24. Abend NS, Gutierrez-Colina AM, Monk HM, Dlugos DJ, Clancy RR. Levetiracetam for treatment of neonatal seizures. Journal of child neurology. 2011;26(4):465-70.
25. Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. Eur J Paediatr Neurol. 2011;15(1):1-7.
26. Nikkhah K, Harati H, Rezaeitalab F, Khosravi A, Anvari Ardakani S. A comparison of the effects of lamotrigine and levetiracetamand lamotrigine and valproate sodium in patients with epilepsy. medical journal of mashhad university of medical sciences. 2016;59(3):132-8.
27. Venkatesan C, Young S, Schapiro M, Thomas C. Levetiracetam for the Treatment of Seizures in Neonatal Hypoxic Ischemic Encephalopathy. J Child Neurol. 2017;32(2):210-4.
28. Shin JW, Jung YS, Park K, Lee SM, Eun HS, Park MS, et al. Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures. Korean journal of pediatrics. 2017;60(2):50-4.
29. Mollamohammadi M, Amirhoseini ZS, Saadati A, Pirzadeh Z, Hassan Amouzadeh M. Oral Levetiracetam as Add-On Therapy in Refractory Neonatal Seizures. Iranian journal of child neurology. 2018;12(4):103-10.
30. Han JY, Moon CJ, Youn YA, Sung IK, Lee IG. Efficacy of levetiracetam for neonatal seizures in preterm infants. BMC pediatrics. 2018;18(1):131.
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