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

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
Intravenous 1 month up to 18 years [10] [11] [19] [40] 40 mg/kg/dose allow to run in over 8 minutes.

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

Barbiturates and derivatives
	Phenobarbital Related Medicines Menu">	N03AA02

Hydantoin derivatives
	Phenytoin Related Medicines Menu">	N03AB02

Succinimide derivatives
	Ethosuximide Related Medicines Menu">	N03AD01

Carboxamide derivatives
	Carbamazepine Related Medicines Menu">	N03AF01

Fatty acid derivatives
	Valproic acid (sodiumvalproate) Related Medicines Menu">	N03AG01

Other antiepileptics
	Lamotrigine Related Medicines Menu">	N03AX09

References

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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
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