Clinical Application Power point

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