Neuropediatrics 2015; 46(05): 329-334
DOI: 10.1055/s-0035-1558969
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Use of Levetiracetam in Neonates in Clinical Practice: A Retrospective Study at a German University Hospital

Martina P. Neininger
1   Drug Safety Center, Department of Clinical Pharmacy, Institute of Pharmacy, University of Leipzig, Leipzig, Germany
,
Michaela Ullmann
1   Drug Safety Center, Department of Clinical Pharmacy, Institute of Pharmacy, University of Leipzig, Leipzig, Germany
,
Anna J. Dahse
1   Drug Safety Center, Department of Clinical Pharmacy, Institute of Pharmacy, University of Leipzig, Leipzig, Germany
2   Drug Safety Center, Pharmacy of the University Hospital, Leipzig, Germany
,
Steffen Syrbe
3   Centre for Paediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
,
Matthias K. Bernhard
3   Centre for Paediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
,
Roberto Frontini
2   Drug Safety Center, Pharmacy of the University Hospital, Leipzig, Germany
,
Wieland Kiess
3   Centre for Paediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
,
Andreas Merkenschlager
3   Centre for Paediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
,
Ulrich Thome
4   Division of Neonatology, Centre for Paediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
,
Thilo Bertsche*
1   Drug Safety Center, Department of Clinical Pharmacy, Institute of Pharmacy, University of Leipzig, Leipzig, Germany
,
Astrid Bertsche*
3   Centre for Paediatric Research, University Hospital for Children and Adolescents, Leipzig, Germany
› Author Affiliations
Further Information

Publication History

25 March 2015

16 June 2015

Publication Date:
26 August 2015 (online)

Abstract

Objective We performed a retrospective chart analysis in neonates routinely treated with levetiracetam (LEV) in a university setting.

Patients and Methods We assessed clinical characteristics of the included neonates. Documented LEV doses and the duration of treatment were evaluated. To assess LEV effectiveness, we compared the need of any additional anticonvulsant as co- and rescue therapies before and following the initiation of LEV treatment. To assess LEV tolerance, we sought to identify documented adverse drug reactions resulting in a termination of LEV treatment.

Results We analyzed a total of 72 neonates receiving LEV with a median gestational age at initiation of LEV treatment of 30 4/7 gestational weeks (min., 245/7/max., 430/7 weeks). LEV was applied in target doses of 41.7 mg/kg/d (min., 14.4/max., 106.2 mg/kg/d). Patients received LEV treatment at hospital for a median of 28 days (min., 1/max., 195 days). Additional anticonvulsant therapy decreased a week after LEV treatment was initiated (p = 0.008). We did not find any cases of terminated LEV treatment resulting from adverse drug reactions.

Conclusion Long term use of high LEV doses is rather frequent in immature neonates. Our data indicate good effectiveness and a low risk of adverse drug reactions.

* The authors, Thilo Bertsche and Astrid Bertsche, contributed equally to this work.


 
  • References

  • 1 Berg AT, Jallon P, Preux PM. The epidemiology of seizure disorders in infancy and childhood: definitions and classifications. Handb Clin Neurol 2013; 111: 391-398
  • 2 Vento M, de Vries LS, Alberola A , et al. Approach to seizures in the neonatal period: a European perspective. Acta Paediatr 2010; 99 (4) 497-501
  • 3 Bittigau P, Sifringer M, Genz K , et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A 2002; 99 (23) 15089-15094
  • 4 Bittigau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann N Y Acad Sci 2003; 993: 103-114 , discussion 123–124
  • 5 Forcelli PA, Kim J, Kondratyev A, Gale K. Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain. Epilepsia 2011; 52 (12) e207-e211
  • 6 Forcelli PA, Kozlowski R, Snyder C, Kondratyev A, Gale K. Effects of neonatal antiepileptic drug exposure on cognitive, emotional, and motor function in adult rats. J Pharmacol Exp Ther 2012; 340 (3) 558-566
  • 7 Sulzbacher S, Farwell JR, Temkin N, Lu AS, Hirtz DG. Late cognitive effects of early treatment with phenobarbital. Clin Pediatr (Phila) 1999; 38 (7) 387-394
  • 8 Manthey D, Asimiadou S, Stefovska V , et al. Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain. Exp Neurol 2005; 193 (2) 497-503
  • 9 Kilicdag H, Daglıoglu K, Erdogan S , et al. The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury. Early Hum Dev 2013; 89 (5) 355-360
  • 10 Komur M, Okuyaz C, Celik Y , et al. Neuroprotective effect of levetiracetam on hypoxic ischemic brain injury in neonatal rats. Childs Nerv Syst 2014; 30 (6) 1001-1009
  • 11 Griesmaier E, Stock K, Medek K , et al. Levetiracetam increases neonatal hypoxic-ischemic brain injury under normothermic, but not hypothermic conditions. Brain Res 2014; 1556: 10-18
  • 12 Talos DM, Chang M, Kosaras B , et al. Antiepileptic effects of levetiracetam in a rodent neonatal seizure model. Pediatr Res 2013; 73 (1) 24-30
  • 13 Koppelstäetter A, Bührer C, Kaindl AM. Treating Neonates with Levetiracetam: a survey among German University Hospitals [in German]. Klin Padiatr 2011; 223 (7) 450-452
  • 14 Abend NS, Gutierrez-Colina AM, Monk HM, Dlugos DJ, Clancy RR. Levetiracetam for treatment of neonatal seizures. J Child Neurol 2011; 26 (4) 465-470
  • 15 Fürwentsches A, Bussmann C, Ramantani G , et al. Levetiracetam in the treatment of neonatal seizures: a pilot study. Seizure 2010; 19 (3) 185-189
  • 16 Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol 2011; 44 (4) 265-269
  • 17 Khan O, Cipriani C, Wright C, Crisp E, Kirmani B. Role of intravenous levetiracetam for acute seizure management in preterm neonates. Pediatr Neurol 2013; 49 (5) 340-343
  • 18 Rakshasbhuvankar A, Rao S, Kohan R, Simmer K, Nagarajan L. Intravenous levetiracetam for treatment of neonatal seizures. J Clin Neurosci 2013; 20 (8) 1165-1167
  • 19 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
  • 20 Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res 2012; 72 (1) 43-49
  • 21 Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. J Perinatol 2013; 33 (11) 841-846
  • 22 AWMF online (homepage on the Internet) . C. Roll, R. Korinthenberg, A. Merkenschlager, G. Jorch. Leitlinie der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin und der Gesellschaft für Neuropädiatrie Zerebrale Anfälle beim Neugeborenen. Updated August 22, 2012. Available at: http://www.awmf.org/uploads/tx_szleitlinien/024-011l_S2k_Zerebrale_Anf%C3%A4lle_beim_Neugeborenen_08-2012_1_.pdf . Accessed March 25, 2015