Levetiracetam is an antiepileptic drug approved to treat partial onset seizures in infants and children aged 1 month and older. It is also commonly used off-label to treat neonatal seizures caused by various conditions. Levetiracetam has favorable pharmacokinetic and safety profiles. It has minimal drug interactions and side effects in neonates are typically somnolence and irritability. The document advocates for interprofessional collaboration to improve care for neonates with seizures through integrating research on seizure management best practices into clinical settings.

1. LEVETIRACETAM
Clinical Application Paper
Blenda Kay Gregorio
11/15/2015

2. LEVETIRACETAM
 Approved in 2012 as an adjunctive therapy for
partial onset seizures in infants and children 1
month of age and older with epilepsy
 47% of pediatric neurologists recommend off
label use for the treatment of neonatal seizures
 Used off-label to treat neonatal seizures caused
by hypoxic-ischemic encephalopathy from
asphyxia, metabolic disturbances,
cerebrovascular disease, infection, and
congenital malformations

3. INTENDED DRUG RESPONSE
 Binds to GABA
receptors(Inhibitory
neurotransmitter)
 Inhibits excitatory effect
of glutamate(excitatory
neurotransmitter)
 Causes neuronal
apoptosis in animal
models
 Less than 50% effective
 Selectively binds to
brain cell membranes
 Binds to synaptic
vesicle protein SV2a
 Impedes
neurotransmitter
release
 Decreases neuronal
excitability
Phenobarbital Levetiracetam

4. POTENTIAL INTERACTIONS
 30% increase in clearance in children co-
medicated with enzyme inducers such as
phenobarbital
 Longer half-life in neonates
 Increase dosing interval
 Higher volume of distribution in neonates
 Higher loading dose on a mg/kg basis
than adults and older children
 Primarily excreted unchanged in urine
 May need to monitor for renal dysfunction

5. ADVERSE DRUG REACTIONS
LEVETIRACETAM
Low potential for drug interactions
No metabolism in liver
Insignificant protein binding (<10%)
Clearance increased 30% in infants
co-medicated with enzyme-inducer
(phenobarbital)
May need to increase dose

6. SIDE EFFECTS
LEVETIRACETAM
Only 2 side effects reported in
neonates & children
Somnolence
Irritability (children)
Thought to be the result of
rapid up-titration

7. PHARMACOKINETICS OF LEVETIRACETAM
 Ideal antiepileptic drug
 Wide therapeutic index
 Benign safety profile
 Rapid absorption following oral dose (>95%)
 Excellent bioavailability (nearly 100%)
 Quickly achieves steady-state concentrations
 Linear kinetics
 Minimal plasma protein binding
 Not metabolized in the liver

8. DRUG BINDING ISSUES
LEVETIRACETAM
Minimally bound to plasma
proteins
>60% excreted unchanged in
urine
Metabolism is not dependent on
liver cytochrome P450
isoenzymes

9. CLINICAL APPLICATION PAPER TO IMPROVE
COMMUNICATION
Interprofessional collaboration
improves patient safety, quality of care,
and outcomes
Collaboration across disciplines
improves outcomes and builds team
work
Interprofessional collaboration can
influence advances in the care of
neonates with seizures

10. APPLICATION TO PRACTICE SETTING
 Identify current peer reviewed literature on the etiology,
recognition, and management of neonatal seizures
including the clinical application paper
 Form an interprofessional team to champion the cause
of improved safety and patient outcomes in neonates
with seizures
 Effectively translate research data into clinical practice
to improve seizure management of neonates by
identifying potentially better practices
 Use seizure management champions to facilitate
adoption of best practices for infants with seizures

11. REFERENCES
CLINICAL APPLICATION PAPER 1
References
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