Newer antiepileptic drug levetiracetam in pediatric

Levetiracetam

● Levetiracetam (LEV) was recently approved for use as add-on therapy in children with
partial seizures and now provides another alternative in the treatment of pediatric
epilepsy.
● Levetiracetam is a broad spectrum AED which selectively inhibits high-voltage-activated
calcium channels and reduces calcium release from intraneuronal stores [1].
● It also binds to a specific target in the brain, the synaptic vesicle protein 2A (SV2A), an
integral membrane glycoprotein, which is involved in the control of vesicle fusion and
exocytosis.
● The pharmacokinetic profi le of LEV appears similar in pediatric patients compared with
adults, except that the drug is cleared more quickly. Body clearance is 30% to 40% higher
and the half-life is decreased to about 6 hours.
● Higher doses of LEV (on a mg/kg basis) may be required in children to accommodate their
increased clearance

Indications:
● Levetiracetam is effective as adjunctive therapy in pediatric patients with partial onset
seizures and in primary generalized tonic-clonic seizures [2]. Intravenous preparation has
recently shown efficacy in neonatal seizures 3] and status epilepticus [4].

Efficacy:
● In a randomized, double-blind, placebo-controlled, multicenter trial in 101 children with
refractory partial seizures, >50% seizure reductions was seen in 44.6% receiving
levetiracetam and 19.6% in patients receiving placebo [5].
● Levetiracetam has been evaluated in childhood epilepsy syndromes including rolandic
epilepsy [6], electrical status epilepticus in slow sleep, myoclonic and tonic clonic seizures
of Lennox Gastaut syndrome [7] and as an alternative to valproate in juvenile myoclonic
epilepsy in adolescent girls [8].
● Beneficial effects on language development have been reported [9].

Advantages:
● Levetiracetam has a favourable pharmacokinetic profile in terms of safety in patients with
liver disease and minimal drug interaction with other AEDs.

Side effect:
● Levetiracetam is well tolerated in children with minor adverse events like headache,
anorexia, and somnolence. However, there are concerns of behavioural side effects like
aggression, emotional lability, oppositional behavior, and psychosis in children [10].
Dosage:
● Pediatric dose start from 10 mg/kg/day (divided tweice daily) to be hiked by 10-20 mg/kg
every two weeks to a maximum dose of 40-60 mg/kg/day.

Reference:
1. Lukyanetz E, Shkryl V, Kostyuk P. Selective Blockade of N-Type Calcium Channels by
Levetiracetam. Epilepsia. 2002;43(1):9-18.
2. Verrotti A, DʼAdamo E, Parisi P, Chiarelli F, Curatolo P. Levetiracetam in Childhood
Epilepsy. Pediatric Drugs. 2010;12(3):177-186.
3. Lukyanetz E, Shkryl V, Kostyuk P. Selective Blockade of N-Type Calcium Channels by
Levetiracetam. Epilepsia. 2002;43(1):9-18.
4. Kneen R, Kumar R, Spinty S, Appleton R. Intravenous levetiracetam in acute repitive
seizures and status epilepticus in children: experience from a children’s hospital. Seizure.
2012;21:529-34.
5. Kossoff EH, Bergey GK, Freeman JM, Vining EP. Levetiracetam psychosis in children
with epilepsy. Epilepsia. 2001;42:1611-3.
6. Verrotti A, Coppola G, Manco R, Ciambra G, Iannetti P, Grosso S, et al. Levetiracetam
monotherapy for children and adolescents with benign rolandic seizures. Seizure.
2007;16:271-5.
7. de los Reyes E, Sharp G, Williams J, Hale S. Levetiracetam in the treatment of Lennox-
Gastaut syndrome. Pediatr Neurol. 2004;30(4):254-256.
doi:10.1016/j.pediatrneurol.2003.09.007
8. Verrotti A, Cerminara C, Coppola G, Franzoni E, Parisi P, Iannetti P, et al. Levetiracetam
in juvenile myoclonic epilepsy: long-term efficacy in newly diagnosed adolescents. Dev
Med Child Neurol. 2008;50:29-32.
9. Kossoff E, Los J, Boatman D. A pilot study transitioning children onto levetiracetam
monotherapy to improve language dysfunction associated with benign rolandic
epilepsy. Epilepsy & Behavior. 2007;11(4):514-517. doi:10.1016/j.yebeh.2007.07.
10. Kossoff E, Bergey G, Freeman J, Vining E. Levetiracetam Psychosis in Children with
Epilepsy. Epilepsia. 2001;42(12):1611-1613. doi:10.1046/j.1528-1157.2001.32101.x