1. Seizure Incidence Associated with Bupropion Dosing Errors Reported to a Local Poison Center William Eggleston, PharmD 1 and Ross W. Sullivan, MD 1,2 1 SUNY Upstate Medical University, Upstate NY Poison Center, Syracuse, NY 2 SUNY Upstate Medical University, Department of Emergency Medicine, Syracuse, NY Immediate and delayed seizures are reported with bupropion exposure Seizures associated with therapeutic use, abuse, and overdose Epidemiological data suggests an increased seizure risk at doses >450 mg compared to doses ≤ 450 mg Increased prescribing with newer indications Antidepressant, smoking cessation, weight loss, and ADHD Management criteria at the Upstate New York Poison Center dictates a 24 hour observation for doses >450mg Lack of literature assessing seizure risk associated with a single supratherapeutic dose Chronic bupropion doses >450 mg are associated with seizures IR: ten-fold increase between 450-600 mg SR: 300mg/day = 0.1% vs. 450 mg/day = 0.4% incidence XL: not formally evaluated in clinical trials Literature indicates significant toxicity with overdose and abuse Seizures and cardiac dysrhythmias Unknown seizure risk after supratherapeutic dose Accidental double dose of 300 mg bupropion XL results in a 24-hour hospitalization No patients seized after a single supratherapeutic dose A total of 14 (44%) patients ingested ≤600 mg An observation dose of >600 mg would have prevented 1.93 hospitalizations per year Based on 2013 CMS data savings would equate to: NY- $37,164/year US States/Territories: $603,087 Limitations Poison Center Data likely underreported Small population, isolated to a single Poison Center Cost savings analysis assumes equal rate of exposure in each state Methods The risk for seizure after an acute exposure to > 450 mg bupropion remains unclear Data from a single Poison Center revealed no seizures after a single dose >450 mg bupropion Future study Obtain a larger national data set of bupropion ingestions due to therapeutic error to assess the incidence of seizures Determine if there is a significantly increased seizure risk after acute exposure to 600 mg of bupropion in patients chronically taking the medication Retrospective review of Upstate NY Poison Center data All bupropion exposures reported from January 1, 2008 to April 1, 2015 were included for analysis (Figure 1) Inclusion criteria Cases coded as unintentional therapeutic error Reported ingestion >450 mg Exclusion criteria Coingestants reported Unknown dose Unknown outcome Patient not chronically taking bupropion Data collected (if reported) Age, gender, dose ingested, preparation ( i.e. SR or XR), duration of exposure, seizure reported, time to onset of seizure (Figure 1) Figure 1: Demographic data from cases included for analysis 460 cases were identified and 37 met criteria for review Demographic data was collected (Figure 2) Exposures were further classified to differentiate between acute and chronic supratherapeutic exposures 32 acute supratherapeutic exposures were identified Mean dose ingested: 909 mg (range 600-2250 mg) No seizures reported 5 chronic supratherapeutic exposures identified One seizure reported Case: patient ingested 300 mg bupropion SR twice daily for 7 days prior to seizure activity Introduction Results DemographicResult Mean age (range)37 years (16-59 years) Female78% (29/37) Acute single exposure32 (86%) Mean dose (acute)909 mg (600-2250 mg) Figure 2: Bupropion formulation reported in cases included for analysis Discussion Conclusion