Levetiracetam

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