title: Association between concomitant use of several systemic NSAIDs and an excess risk of adverse drug reaction. A case/non-case study from the French Pharmacovigilance system database.
abstract: OBJECTIVE
  To examine whether the risk of some selected adverse effects increases with the number of systemic non-steroidal anti-inflammatory (NSAID) drugs.
  
  
  METHODS
  The French Pharmacovigilance database was examined for an association between drug reaction reports and the exposure to one and two or more NSAIDs using a case/non-case study design. In the analysis, 54,583 spontaneous reports of adverse drug reactions were included, consisting of 2270 reports of hepatic injury, 994 reports of acute renal failure, 194 reports of gastrointestinal bleeding and 525 reports of angioedema, among others.
  
  
  RESULTS
  Use of NSAIDs significantly increased the risk of hepatic injury, gastrointestinal bleeding, acute renal failure and angioedema. The odds ratios tended to increase with the number of NSAIDs for hepatic injury, gastrointestinal bleeding and acute renal failure but not for angioedema. In comparison with reports that did not mention any use of NSAIDs, the odds ratios associated with the use of a single NSAID and two or more NSAIDs were respectively 1.2 (95%CI: 0.9-1.5) and 2.2 (95%CI: 1.3-3.8) for hepatic injury, 7.3 (95%CI: 4.9-10.9) and 10.7 (95%CI: 2.9-40.2) for gastrointestinal bleeding, 3.2 (95%CI: 2.5-4.1) and 4.8 (95%CI: 2.6-8.8) for acute renal failure. For angioedema, the odds ratios were roughly similar when a single NSAID (OR=2.7; 95% CI: 2.2-3.4) or two or more NSAIDs (OR=2.0; 95%CI: 0.7-6.0) were used. The risk of severe ADRs (hepatic injury and acute renal failure) was six- to sevenfold higher in reports mentioning concomitant use of two NSAIDs or more than in those that did not.
  
  
  CONCLUSIONS
  This study shows that concomitant use of two or more NSAIDs was associated with an excess risk of adverse effects such as hepatic injury, acute renal failure and gastrointestinal bleeding. Although simultaneous use of several systemic NSAIDs has no pharmacological justification, this may raise a serious public health problem with the increasing use of over-the-counter non-steroidal anti-inflammatory agents.
authors.affiliation: GEREPT-Centre d'Epidémiologie de Population de Bourgogne, Facultés de Médecine et Pharmacie, 7 bd Jeanne d'Arc, BP 87900, 21079 Dijon Cedex, France. fclinard@u-bourgogne.fr
authors.forename: François
authors.initials: F
authors.lastname: Clinard
authors.forename: Catherine
authors.initials: C
authors.lastname: Sgro
authors.forename: Marc
authors.initials: M
authors.lastname: Bardou
authors.forename: Patrick
authors.initials: P
authors.lastname: Hillon
authors.forename: Monique
authors.initials: M
authors.lastname: Dumas
authors.forename: Carmen
authors.initials: C
authors.lastname: Kreft-Jais
authors.forename: André
authors.initials: A
authors.lastname: Escousse
authors.forename: Claire
authors.initials: C
authors.lastname: Bonithon-Kopp
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005602:France; D006801:Humans
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal