SPONTANEOUS REPORTING OF ADVERSE DRUG-REACTIONS TO NONSTEROIDAL ANTIINFLAMMATORY DRUGS - A REPORT FROM THE SPANISH SYSTEM OF PHARMACOVIGILANCE, INCLUDING AN EARLY ANALYSIS OF TOPICAL-COATED AND ENTERIC-COATED FORMULATIONS

Non-steroidal anti-inflammatory drugs (NSAIDs) are the third most comm only prescribed group of drugs in Spain. We present here the profile o f adverse drug reactions (ADRs) attributed to them and reported to the Spanish System of Pharmacovigilance (SSPV) between 1983 and 1991, tog ether with a preliminary analysis of topical, slow-release (SR) and en teric-coated (EC) preparations. Out of 18 348 reports of ADRs included in the SSPV database, 1609 (8.8 %) implicated an NSAID. NSAIDs ranked second after antibiotics (15.1 % of all reports) among the most commo nly implicated drugs. Half of the patients were more than 55 years old , and 60 % were women. Diclofenac (364 reports), piroxicam (282), indo methacin (197), naproxen (155), and ketoprofen (137) were the most com monly implicated NSAIDs in reports of ADRs. The most commonly reported ADRs were gastrointestinal (39 %), cutaneous (20 %), and those affect ing the central and peripheral nervous system (9 %). Seven reactions h ad a fatal outcome, and 138 were considered life threatening. Forty-ni ne reports included previously undescribed ADRs. There were 98 reports describing ADRs attributed to topical NSAIDs; 5 of these described 11 general reactions, such as duodenal ulcer, gastrointestinal bleeding, diarrhoea, dyspnoea, facial oedema, aggravation of bronchospasm, and angioedema. One hundred and sixty-eight reports referred to SR and EC preparations. The ratio of gastrointestinal to non-gastrointestinal re actions to SR-EC diclofenac was higher in the case of SR-EC diclofenac than in the case of plain diclofenac (P = 0.037); similarly, the rati o of CNS to non-CNS reactions to SR-EC indomethacin was also higher th an the corresponding ratio with plain indomethacin (P = 0.002). Althou gh differential selective reporting of these preparations cannot be ex cluded, these results raise doubts about the relative safety of SR and EC preparations of NSAIDs in practice.