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Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug‐induced liver injury case–control study in Italy
Author(s) -
Donati Monia,
Conforti Anita,
Lenti Maria Carmela,
Capuano Annalisa,
Bortolami Oscar,
Motola Domenico,
Moretti Ugo,
Vannacci Alfredo,
Rafaniello Concetta,
Vaccheri Alberto,
Arzenton Elena,
Bonaiuti Roberto,
Sportiello Liberata,
Leone Roberto
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.12938
Subject(s) - nimesulide , medicine , odds ratio , liver injury , ibuprofen , confidence interval , gastroenterology , drug , dose , ketoprofen , diclofenac , anesthesia , pharmacology
Aim Drug‐induced liver injury is one of the most serious adverse drug reactions and the most frequent reason for restriction of indications or withdrawal of drugs. Some nonsteroidal anti‐inflammatory drugs (NSAIDs) were withdrawn from the market because of serious hepatotoxicity. We estimated the risk of acute and serious liver injury associated with the use of nimesulide and other NSAIDs, with a prevalence of use greater than or equal to 5%. Methods This is a multicentre case–control study carried out in nine Italian hospitals from October 2010 to January 2014. Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders not related to chronic conditions, not involving the liver. Adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated initially with a bivariate and then multivariate analysis. Results We included 179 cases matched to 1770 controls. Adjusted OR for acute serious liver injury associated with all NSAIDs was 1.69, 95% CI 1.21–2.37. Thirty cases were exposed to nimesulide (adjusted OR 2.10, 95% CI 1.28–3.47); the risk increased according to the length of exposure (OR > 30 days: 12.55, 95% CI 1.73–90.88) and to higher doses (OR 10.69, 95% CI 4.02–28.44). Risk of hepatotoxicity was increased also for ibuprofen, used both at recommended dosages (OR 1.92, 95% CI 1.13–3.26) and at higher doses (OR 3.73, 95% CI 1.11–12.46) and for ketoprofen ≥ 150 mg (OR 4.65, 95% CI 1.33–10.00). Conclusion Among all NSAIDs, nimesulide is associated with the higher risk, ibuprofen and high doses of ketoprofen are also associated with a modestly increased risk of hepatotoxicity.