Neonatal Intensive Care Drug Manual

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Pharmacokinetics: Have not been reported in preterm infants.[1] The half-life in neonates is longer compared to older children.[1] Peak plasma concentrations are achieved at 1.4 hours after an oral dose. Median half-life was reported to be 18.5 ± 7.1 hours on day 1 and averaged approximately 9 hours (range 3–13 hours) when assessed day 7–30. Over the first week, the CL increases into the range of older children.[1] The CL is lower in neonates and infants with renal impairment requiring monitoring of trough concentrations and dose adjustment.[1, 2] In children, the clearance was reported to be increased by 30% with co-administration of phenobarbital (phenobarbitone), carbamazepine and phenytoin.[11] In children aged 2–46 months, oral administration is characterised by rapid absorption, resulting in peak plasma concentrations within 1.4 hours of dosing and a half-life 5 hours.[12] Recommendations are to target levetiracetam trough concentration > 20 mg/L when seizure frequency is high and —10 - 40 mg/L subsequently titrated to seizure control.[1, 2, 16]

References

1. Loiacono G, Masci M, Zaccara G, Verrotti A. The treatment of neonatal seizures: focus on levetiracetam. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstet. 2016;29:69-74.

2. 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. Pediatric research. 2012;72:43-9.

3. Egunsola O, Choonara I, Sammons HM. Safety of Levetiracetam in Paediatrics: A Systematic Review. PloS one. 2016;11:e0149686.

4. St Louis EK, Gidal BE, Henry TR, Kaydanova Y, Krumholz A, McCabe PH, Montouris GD, Rosenfeld WE, Smith BJ, Stern JM, Waterhouse EJ, Schulz RM, Garnett WR, Bramley T. Conversions between monotherapies in epilepsy: expert consensus. Epilepsy & Behavior. 2007;11:222-34.

5. Abend NS, Gutierrez-Colina AM, Monk HM, Dlugos DJ, Clancy RR. Levetiracetam for treatment of neonatal seizures. Journal of child neurology. 2011;26:465-70.

6. Furwentsches A, Bussmann C, Ramantani G, Ebinger F, Philippi H, Poschl J, Schubert S, Rating D, Bast T. Levetiracetam in the treatment of neonatal seizures: a pilot study. Seizure. 2010;19:185-9.

7. 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;44:265-9.

8. Rakshasbhuvankar A, Rao S, Kohan R, Simmer K, Nagarajan L. Intravenous levetiracetam for treatment of neonatal seizures. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2013;20:1165-7.

9. Ramantani G, Ikonomidou C, Walter B, Rating D, Dinger J. Levetiracetam: safety and efficacy in neonatal seizures. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2011;15:1-7.

10. Khan O, Cipriani C, Wright C, Crisp E, Kirmani B. Role of intravenous levetiracetam for acute seizure management in preterm neonates. Pediatric neurology. 2013;49:340-3.

11. Dahlin MG, Wide K, Ohman I. Age and comedications influence levetiracetam pharmacokinetics in children. Pediatric neurology. 2010;43:231-5.

12. Glauser TA, Mitchell WG, Weinstock A, Bebin M, Chen D, Coupez R, Stockis A, Lu ZS. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia. 2007;48:1117-22.

13. UCB Pharma, Keppra Oral Infusion Product Information, 2012.

14. Trissel's 2 Clinical Pharmaceutics Database (Parenteral Compatibility): levetiracetam monograph accessed via Micromedex 04/09/2014.

15. UCB Pharma, Keppra IV Infusion Product Information, 2012.

16. Patsalos PN1, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, Leppik IE, Tomson T, Perucca E. Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008 Jul;49(7):1239-76. doi: 10.1111/j.1528-1167.2008.01561.x.

Original version Date: 17/02/2016	Author: Neonatal Medicines Formulary Consensus Group
Current Version number: 1	Version Date: 24/11/2017
Risk Rating: Low	Due for Review: 24/11/2022
Approved by: DTC	Approval Date: TBA

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