Abstracts

Rationale: Perampanel (PER) is approved for adjunctive use in patients 12 and older and has been used extensively in children at Le Bonheur Children’s Hospital.  PER is metabolized by the hepatic enzyme CYP3A4 and enzyme-inducing anti-epileptic drugs (EIAED) taken concomitantly are expected to influence PER serum levels, thus affecting PER efficacy. This study was designed to investigate PER serum levels of  pediatric patients prescribed PER between January 2013 and May 2017. We also want to examine the effect of concomitant EIAEDs on PER serum levels. We hypothesize that the PER serum levels of patients concomitantly prescribed an EIAED will be significantly lower than PER serum levels of patients not concomitantly prescribed an EIAED. Methods: We performed a retrospective chart review and data extraction of patients’ age, gender, PER serum level, weight, prescribed PER dose, and concomitant medications.  Exclusion criteria included patients who were prescribed PER but in whom no serum levels were assayed. Patients were categorized into age groups (0<2, 2<6, 6<12, 12+ years; age distribution of 2, 17, 21, and 47 patients respectively), and organized by serum level and concomitant drug category (on inducing CYP3A4 drugs or not on inducing CYP3A4 drugs). The EIAEDs that were considered to be CYP3A4 inducing are carbamazepine, felbamate, oxcarbazepine, eslicarbazepine, pentobarbital, phenobarbital, phenytoin, rufinamide, topiramate, rifampin, and dexamethasone. Results: Of the 140 total patients who have been prescribed PER within the relevant time frame, 87 patients with a total of 155 PER serum levels were included in the study. Forty-one of these patients, having a total of 72 PER serum levels assayed, were prescribed a concomitant EIAED.  Univariate analysis was performed on average mg/kg dose and average PER level within each age group between concomitant drug categories and age groups. When evaluating all patients prescribed PER, the dose did not significantly differ between patients on EIAEDs and patients not on EIAEDs (p=0.633); however, PER serum levels were significantly higher in patients not concomitantly taking EIAEDs (p=0.044). Prescribed PER mg/kg doses for the 2<6 age group (p=0.000) and the 6<12 age group (p=0.006) were each significantly greater than the 12+ age group; however, PER levels did not differ between age groups (p=0.808).  Serum levels were within the range previously reported for adults on therapeutic doses of PER.                            Conclusions: EIAEDs can alter the serum levels of other anti-epileptic drugs. This is an important interaction to be aware of when prescribing perampanel in the adjunct care of pediatric epilepsy, especially in patients whose epilepsy is refractory to multiple medications and treatment.  In a polytherapy regimen, enzyme inducing drugs and other pharmacodynamic factors must be considered when determining appropriate medication doses. Funding: Shainberg Neuroscience Fund