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
A. Figueras et al., 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, European Journal of Clinical Pharmacology, 47(4), 1994, pp. 297-303
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.