Levetiracetam

Generic name
Levetiracetam
Brand name
ATC Code
N03AX14
Compare …

Levetiracetam

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

 

  Cmax (2x 1000 mg) Tmax t½ Cl Vd
1 month to 4 years - 1 hour 5.3 hours 1.5 ml/min/kg -
4-12 yrs - 0.5-1 hour 5 hours 1.1 ml/min/kg -
>12 yrs 43 mcg/ml 1.3 hours - - 0.5-0.7 l/kg
> 18 yrs 43 mcg/ml 1.3 hours 7 ± 1 hour 0.96 ml/min/kg 0.5-0.7 l/kg

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Go to:

Epilepsy
  • Oral
    • 1 month up to 18 years
      [7] [8] [14] [22] [26] [35] [39]
      • Initial dose: 10 mg/kg/day in 2 doses.
      • Maintenance dose: increase to 20 - 40 mg/kg/day in 2 doses. Max: 60mg/kg/day, but not exceeding 3.000 mg/day.
  • Intravenous
    • 1 month up to 18 years
      [2] [34] [36] [39]
      • Initial dose: 10 mg/kg/day in 2 doses.
      • Maintenance dose: Increase to 20 - 40 mg/kg/day in 2 doses. Max: 60mg/kg/day, but not exceeding 3.000 mg/day.
Neonatal epileptic seizures
  • Oral
    • Premature neonates Gestational age < 36 weeks
      [17] [30] [33]
      • Initial dose: With and without hypothermia: 20 mg/kg/dose, as required repeat at most twice with at least 10 min between each dose.
      • Maintenance dose: 20 - 40 mg/kg/day in 2 doses. Max: 60 mg/kg/day.

      • If seizures have stopped: no continuation of anti-epileptic treatment after acute phase (asphyxia)  unless there are abnormalities on the MRI or a genetic cause.


    • Full-term neonates Gestational age ≥ 36 weeks
      [17] [28] [30] [33]
      • Initial dose: With and without hypothermia: 20 mg/kg/dose, as required repeat at most twice with at least 10 min between each dose.
      • Maintenance dose: Increase initial dose with increments of 10 mg/kg every 3 days to 20 - 40 mg/kg/day in 2 doses. Max: 60 mg/kg/day.

      • If seizures have stopped: no continuation of anti-epileptic treatment after acute phase (asphyxia)  unless there are abnormalities on the MRI or a genetic cause.


  • Intravenous
    • Premature neonates: Gestational age < 36 weeks
      [6] [12] [21] [28] [29] [32] [33] [41]
      • Initial dose: With and without hypothermia: 20 mg/kg/dose, as required repeat at most twice with at least 10 min between each dose.
      • Maintenance dose: 20 - 40 mg/kg/day in 2 doses. Max: 60 mg/kg/day.

      • Higher maintenance doses of up to 100 mg/kg/day have also been used in the literature [Abend et al. 2011; Shin et al. 2017; Venkatesan et al. 2017]

        If seizures have stopped: no continuation of anti-epileptic treatment after acute phase (asphyxia)  unless there are abnormalities on the MRI or a genetic cause.

    • Full-term neonates Gestational age ≥ 36 weeks
      [6] [12] [21] [28] [29] [32] [33] [41]
      • Initial dose: With and without hypothermia: 20 mg/kg/dose, as required repeat at most twice with at least 10 min between each dose.
      • Maintenance dose: 20 - 40 mg/kg/day in 2 doses. Max: 60 mg/kg/day.

      • Higher maintenance doses of up to 100 mg/kg/day have also been used in the literature [Abend et al. 2011; Shin et al. 2017; Venkatesan et al. 2017]

        If seizures have stopped: no continuation of anti-epileptic treatment after acute phase (asphyxia)  unless there are abnormalities on the MRI or a genetic cause.
Persistent status epilepticus
Epilepsy, myoclonic attacks
  • Oral
    • 1 month up to 18 years
      • Initial dose: 10 mg/kg/day in 2 doses.
      • Maintenance dose: Increase to 20 - 40 mg/kg/day in 2 doses. Max: 60mg/kg/day, but not exceeding 3.000 mg/day.
  • Intravenous
    • 1 month up to 18 years
      • Initial dose: 10 mg/kg/day in 2 doses.
      • Maintenance dose: Increase to 20 - 40 mg/kg/day in 2 doses. Max: 60mg/kg/day, but not exceeding 3.000 mg/day.

Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2
66 percentage of single dose and dosing interval : 12 uur
GFR 30-50 ml/min/1.73 m2
50 percentage of single dose and dosing interval : 12 uur
GFR 10-30 ml/min/1.73 m2
33 percentage of single dose and dosing interval : 12 uur
GFR < 10 ml/min/1.73 m2
Generalized recommendations cannot be given.
Clinical consequences

The renal clearance of levetiracetam is less and the half-life extended when the renal function is reduced. The risk of side effects is elevated as a result.

Dose-related side effects include sleepiness, asthenia, headaches, dizziness, sleeplessness, amnesia, ataxia, depression, abnormal behaviour, confusion, irritation, emotional lability, aggression, nervousness, hallucinations and double vision.

Patients on dialysis

HD: oplaaddosis 150% normale startdosis, maximale keerdosis 67%, doseerinterval 24 uur; na dialyse een supplementaire dosis van 50-100% normale startdosis

CVVH: startdosering 100%, maximale keerdosis 67%, doseerinterval 12 uur

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

In children from 1 month to 4 years of age, in particular: irritation, abnormal coordination. In children aged 4–16 years: vomiting, agitation, mood change, abnormal behaviour, lethargy and aggression.

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Adjust the dose in renal function disorders. When stopping treatment with levetiracetam, phase it out gradually: in children of > 6 months and adolescents of < 50 kg in steps of 10 mg/kg twice daily every two week and in infants of 1–6 months in steps of 7 mg/kg (maximum twice daily) every two weeks.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ANTIEPILEPTICS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Barbiturates and derivatives
N03AA02
Hydantoin derivatives
N03AB02
Succinimide derivatives
N03AD01
Carboxamide derivatives
N03AF01
Fatty acid derivatives
N03AG01
Other antiepileptics
N03AX09

References

  1. Rademaker C.M.A. et al, Geneesmiddelen-Formularium voor Kinderen, 2007
  2. UCB Pharma BV, SPC Keppra EU/1/00/146/001-005 en EU/1/00/136/029, www.ema.europa.eu, Geraadpleegd 30 april 2010, http://www.ema.europa.eu/humandocs/PDFs/EPAR/keppra/emea-combined-h277nl.pdf
  3. Werkgroep Richtlijnen Epilepsie, Epilepsie. Richtlijnen voor diagnostiek en behandeling, Nederlandse Vereniging voor Neurologie en de Nederlandse Liga tegen Epilepsie, Herziene, tweede versie, januari 2006
  4. Smit LS et al, Richtlijnen voor behandeling van neonatale epileptische aanvallen, Nederlands Vlaamse Werkgroep Neonatale Neurologie van de sectie Neonatologie van de NVK en van de Nederlandse Vereniging voor Kinderneurologie, Nieuwe aangepaste versie juni 2012
  5. Kruijff de, CC. et al, Epileptische aanvallen / status epilepticus, leeftijd > 1 maand. 21 Juni 2012, Nederlandse Vereniging voor Kindergeneeskunde
  6. Abend, N. S. et al, Levetiracetam for treatment of neonatal seizures, J Child Neurol, 2011, 26(4), 465-70
  7. Arican, P. et al , Levetiracetam monotherapy for the treatment of infants with epilepsy., Seizure, 2018, 53, 73-77
  8. Berkovic, S. F., et al, Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy., Neurology , 2007, 69(18), 1751-60
  9. Chhun, S., et al, Population pharmacokinetics of levetiracetam and dosing recommendation in children with epilepsy., Epilepsia , 2009, 50(5), 1150-7
  10. Cock, H. R. , Established status epilepticus treatment trial (ESETT)., Epilepsia , 2011, 52 Suppl 8, 50-2
  11. Dalziel, S. R., et al , A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study, BMC Pediatr, 2017, 17(1), 152
  12. Falsaperla, R., et al, Levetiracetam in Neonatal Seizures as First-line Treatment: A Prospective Study., J Pediatr Neurosci , 2017, 12(1), 24-28
  13. Fountain, N. B., et al. ", Prospective assessment of levetiracetam pharmacokinetics during dose escalation in 4- to 12-year-old children with partial-onset seizures on concomitant carbamazepine or valproate, Epilepsy Res , 2007, 74(1), 60-9
  14. Glauser, T. A., et al, Double-blind placebo-controlled trial of adjunctive levetiracetam in pediatric partial seizures., Neurology, 2006, 66(11), 1654-60
  15. Glauser, T. A. et al, Pharmacokinetics of levetiracetam in infants and young children with epilepsy, Epilepsia, 2007, 48(7), 1117-22
  16. Glauser, T. A., et al, Efficacy and safety of levetiracetam in children with partial seizures: an open-label trial., Epilepsia, 2002, 43(5), 518-24
  17. Han, J. Y., et al, Efficacy of levetiracetam for neonatal seizures in preterm infants, BMC Pediatr , 2018, 18(1), 131
  18. Lima-Rogel, V. et al, Population pharmacokinetics of levetiracetam in neonates with seizures, J Clin Pharm Ther, 2018, 43(3), 422-429
  19. Lyttle, M. D. et al, Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: study protocol for a randomised controlled trial. , Trials, 2017, 18(1), 283
  20. Merhar, S. L. et al, Pharmacokinetics of levetiracetam in neonates with seizures, J Pediatr, 2011, 159(1), 152-154.e3
  21. Neininger, M.P. et al, Use of Levetiracetam in Neonates in Clinical Practice: A Retrospective Study at a German University Hospital, Neuropediatrics , 2015, 46(5), 329-34
  22. Noachtar, S. et al, Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures., Neurology , 2008, 70(8), 607-16
  23. NVN., Richtlijn epilepsie; epilepsiesyndromen (bij kinderen) & anti-epileptica, 2015
  24. NVZA., TDM monografie levetiracetam, 2014
  25. Pellock, J.M. et al , Pharmacokinetic study of levetiracetam in children, Epilepsia, 2001, 42(12), 1574-9
  26. Pina-Garza, J.E. et al, Adjunctive levetiracetam in infants and young children with refractory partial-onset seizures, Epilepsia, 2009, 50(5), 1141-9
  27. Rakshasbhuvankar, A. et al, Intravenous levetiracetam for treatment of neonatal seizures." , J Clin Neurosci , 2013, 20(8), 1165-7
  28. Ramantani, G. et al, Levetiracetam: safety and efficacy in neonatal seizures, Eur J Paediatr Neurol, 2011, 15(1), 1-7
  29. Rao, L.M. et al, A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic-ischemic encephalopathy, Epilepsy Behav, 2018, 88, 212-217
  30. Sedighi, M. et al, Efficacy and safety of levetiracetam in the management of seizures in neonates, Neurosciences (Riyadh), 2016, 21(3), 232-5
  31. Sharpe, C.M. et al, 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), 73-9
  32. Shin, J.W. et al, Experience and pharmacokinetics of Levetiracetam in Korean neonates with neonatal seizures, Korean J Pediatr, 2017, 60(2), 50-54
  33. Nederlands Vlaamse Werkgroep Neonatale Neurologie van de Sectie Neonatologie van de NVK en van de Nederlandse Vereniging voor Kinderneurologie, Richtlijn voor behandeling van neonatale epileptische aanvallen bij de prematuur, à terme neonaat zonder of met therapeutische hypothermie, 2018
  34. Snoeck, E. et al, Modeling and simulation of intravenous levetiracetam pharmacokinetic profiles in children to evaluate dose adaptation rules, Epilepsy Res , 2007, 76(2), 140-7
  35. Toublanc, N. et al, Retrospective population pharmacokinetic analysis of levetiracetam in children and adolescents with epilepsy: dosing recommendations, Clin Pharmacokinet , 2008, 47(5), 333-41
  36. UCB Pharma SA. , SPC Keppra intraveneus (EU/1/00/146/030) 01-06-2018, www.ema.europa.eu
  37. UCB Pharma SA. , SPC Keppra oraal (EU/1/00/146/027) 01-06-018, www.ema.europa.eu
  38. Venkatesan, C. et al, Levetiracetam for the Treatment of Seizures in Neonatal Hypoxic Ischemic Encephalopathy., J Child Neurol , 2017, 32(2), 210-14
  39. Weijenberg, A. et al, Levetiracetam Monotherapy in Children with Epilepsy: A Systematic Review., CNS Drugs , 2015, 29(5), 371-82
  40. Wheless, J.W. et al, Rapid infusion of a loading dose of intravenous levetiracetam with minimal dilution: a safety study, J Child Neurol, 2009, 24(8), 946-51
  41. Yau, M.L. et al, Response of levetiracetam in neonatal seizures, World J Clin Pediatr, 2015, 4(3), 45-9

Changes

Therapeutic Drug Monitoring


Overdose