title: Toxicity and clinical outcomes of paliperidone exposures reported to U.S. Poison Centers.
abstract: BACKGROUND
  Paliperidone is an atypical antipsychotic that was approved in the U.S. in 2006, and is also available in Canada, Australia, New Zealand, Europe, and Asia. Information regarding paliperidone overdoses is limited to case reports. Serious toxicity has yet to be reported.
  
  
  OBJECTIVE
  To evaluate the toxicity of paliperidone exposures using a national poison center database.
  
  
  METHODS
  A retrospective, observational case series of single-substance paliperidone cases reported to the National Poison Data System from 2007 to 2012 was conducted. Cases were evaluated for demographics, reason for exposure, clinical effects, treatments, disposition, and coded medical outcomes. For cases with major effects the text fields in poison center charts were evaluated to verify accuracy of coded outcome. The relationship between dose and severity of medical outcome was analyzed for acute exposure cases.
  
  
  RESULTS
  There were 801 paliperidone cases that met inclusion criteria that included 592 persons of 13 years or greater, 67 children of 6-12 years, 140 children of less than 6 years, and 2 unknown ages. Most common reasons for exposure included: suicide attempt (39.6%), unintentional general (21.1%), therapeutic error (15.7%), and adverse drug reaction (11.9%). The most commonly observed clinical effects were drowsiness/lethargy (28.7%), tachycardia (23.3%), and dystonia (14.2%). Most patients were managed in the emergency department (40.3%) or were admitted to a health care facility (HCF) (42.7%). In 564 cases treated in a HCF, treatments included activated charcoal (25.7%), antihistamines (21.1%), and benzodiazepines (9.4%). Medical outcomes were no effect (35.0%), minor (30.8%), moderate (33.7%), and major effect (0.5%). There were no deaths. Of 491 acute exposures, dose was coded for 74.3% of exposures. There was a significant difference in the reported median dose between those with no effect (6 mg) and either minor effect (12 mg; p = 0.047) or moderate effect cases (12 mg; p = 0.020) in 91 children less than 6 years.
  
  
  CONCLUSIONS
  The majority of patients experienced no or minor toxicity and were not admitted for medical care. Although a higher dose was associated with a more serious outcome in children less than 6 years, the data do not provide clear-cut triage guidelines.
authors.affiliation: Department of Pharmacy Practice and Science, Maryland Poison Center, University of Maryland School of Pharmacy , Baltimore, MD , USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Tsay
authors.forename: W
authors.initials: W
authors.lastname: Klein-Schwartz
authors.forename: B
authors.initials: B
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000633:toxicity*; D002648:Child; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011039:Poison Control Centers; D011743:Pyrimidines / Q000633:toxicity*; D012189:Retrospective Studies; D014481:United States
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D000068882:Paliperidone Palmitate