Adverse drug reactions related to the use of NSAIDs with a focus on nimesulide: results of spontaneous reporting from a Northern Italian area.
OBJECTIVE
To analyse and compare the adverse drug reactions (ADRs) associated with the use of nimesulide with those associated with diclofenac, ketoprofen, and piroxicam, reported spontaneously in a northern Italian area (Veneto and Trentino).


METHODS
Data were obtained from the spontaneous reporting system database of Veneto-Trentino, the principal contributor to the Italian spontaneous surveillance system. All case reports that occurred in association with all formulations of the nonsteroidal anti-inflammatory drugs (NSAIDs) under investigation during the period from January 1988 to December 2000, were analysed in detail. Sales data from June 1996 to May 1999 and prescription data, from 1997 to 2000 from the Veneto region were utilised to select the most widely used NSAIDs to be included in the study. The prescription data were also used to look at the drug use in relation to age.


RESULTS
During the study period, 10 608 reports describing 16 571 adverse reactions were entered into the surveillance system. We found 207 case reports for nimesulide, 187 for diclofenac, 174 for ketoprofen, and 137 for piroxicam. Analysis of sales and prescription data revealed that in the Veneto region nimesulide was the most widely prescribed drug followed at a long distance by diclofenac, piroxicam and ketoprofen. No age-related difference in the use of the four drugs was found. Analysis of the case reports revealed significantly different toxicity profiles for the four drugs. In particular, nimesulide was associated with fewer and less severe gastrointestinal (GI) ADRs compared with the other NSAIDs. Nimesulide was associated with about half the number of GI reactions (10.4%) than the other three NSAIDs (21.2% for diclofenac, 21.7% for ketoprofen, 18.6% for piroxicam). Two previously unreported reactions were also found for piroxicam and ketoprofen.


CONCLUSIONS
Nimesulide is the most frequently used NSAID in Italy. Spontaneous reporting data suggest that nimesulide has the most favourable GI tolerability profile of the NSAIDs investigated, with few reports of severe GI reactions. A few reports of hepatic and renal impairment associated with nimesulide suggest caution in patients at risk. Age-related reporting analysis suggests a higher toxicity for diclofenac and piroxicam in the elderly compared with nimesulide and ketoprofen. This analysis of the Veneto-Trentino database on spontaneous reporting confirms that NSAIDs differ in their tolerability profile, and this fact should be taken into account in the choice of drugs in relation to patient characteristics.
Conforti
A
A
Clinical Pharmacology Unit, Reference Centre for Education and Communication within The WHO Programme for International Drug Monitoring, University of Verona, Verona, Italy.
Leone
R
R
Moretti
U
U
Mozzo
F
F
Velo
G
G
D016907:Adverse Drug Reaction Reporting Systems; D000367:Age Factors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016208:Databases, Factual; D004363:Drug Utilization; D006801:Humans; D007558:Italy / Q000453:epidemiology; D011358:Product Surveillance, Postmarketing; D013449:Sulfonamides / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013449:Sulfonamides; C012655:nimesulide