title: Ibuprofen-associated hypothermia in children: analysis of the Italian spontaneous reporting database.
abstract: OBJECTIVE
  An analysis of Italian spontaneous adverse drug reactions (ADR) reporting database highlighted a potential association between hypothermia and ibuprofen in children. Hypothermia is defined as a core body temperature of 35 °C (95 °F). Ibuprofen is the most prescribed NSAID for the treatment of fever and moderate pain in children. We aimed to analyze the cases of ibuprofen-associated hypothermia retrieved in the Italian database in order to contribute to the discussion on this potential association.
  
  
  METHODS
  We extracted all suspected cases of ibuprofen-associated hypothermia from the Italian spontaneous reporting database and from VigiBase up to December 2015. We considered the proportional reporting ratio (PRR) as a measure of disproportionality for the Italian cases and the information component (IC) for the reports from VigiBase. We performed a case-by-case analysis to exclude duplicates.
  
  
  RESULTS
  Nineteen cases of hypothermia associated with ibuprofen use were retrieved from the Italian spontaneous reporting database (PRR 19.8, CI 95 %, 12.0-32.9). The reports concerned ten females and nine males with an average age of 2.5 years. Up to 31 December 2015, 168 cases of hypothermia associated with ibuprofen were reported to VigiBase, with an IC of 2.05 (IC025, 1.82). Among these, 126 cases involved children (49 % males) with an average age of 4.4 years.
  
  
  CONCLUSIONS
  Although the risk of this ADR is unknown so far, the widespread use of this drug recommends the need for further studies to better characterize this possible association. Clinicians and pharmacists but also parents should be aware that this risk is theoretical as not yet been confirmed.
authors.affiliation: Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Donati
authors.affiliation: Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Monaco
authors.affiliation: Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Melis
authors.affiliation: Italian Medicines Agency (Agenzia Italiana del Farmaco AIFA) Pharmacovigilance Office, Via del Tritone 181, 00187, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sottosanti
authors.affiliation: Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Biagi
authors.affiliation: Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vaccheri
authors.affiliation: Unit of Pharmacology, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 48, 40126, Bologna, Italy. domenico.motola@unibo.it.
authors.forename: Domenico
authors.identifier: http://orcid.org/0000-0001-6253-4014
authors.initials: D
authors.lastname: Motola
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced*; D007052:Ibuprofen / Q000009:adverse effects*; D007223:Infant; D007558:Italy; D008297:Male
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007052:Ibuprofen
keywords: Adverse drug reaction; Disproportionality; Fever; NSAID