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Cyclo‐oxygenase selectivity and chemical groups of nonsteroidal anti‐inflammatory drugs and the frequency of reporting hypersensitivity reactions: a case/noncase study in VigiBase
Author(s) -
Bakhriansyah Mohammad,
Meyboom Ronald H.B.,
Souverein Patrick C.,
Boer Anthonius,
Klungel Olaf H.
Publication year - 2019
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12463
Subject(s) - medicine , odds ratio , anti inflammatory , confidence interval , nonsteroidal , sulfonamide , pharmacology , chemistry , stereochemistry
To date, no reports of hypersensitivity reactions ( HSR s) among nonsteroidal anti‐inflammatory drugs ( NSAID s) according to cyclo‐oxygenase ( COX ) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSR s for NSAID s based on their relative inhibitory potency toward COX enzymes and chemical groups, including the presence/absence of a functional sulfonamide group, in strata observed 5 years after market authorization. A case/noncase study was performed among individual case safety reports ( ICSR s) with NSAID s as suspected drugs in VigiBase, the WHO spontaneous reporting database. Cases were ICSR s mentioning angioedema and anaphylactic/anaphylactoid shock conditions, while noncases were ICSR s without HSR s. NSAID s were categorized into (i) NSAID s with high COX ‐2 selectivity (coxibs), (ii) noncoxib NSAID s with COX ‐2 preference, (iii) NSAID s with poor selectivity, or (iv) NSAID s with unknown selectivity. Chemical groups were defined based on the Anatomical Therapeutic Chemical classification system and the presence/absence of a functional sulfonamide group. Reporting odds ratios ( ROR s) and 95% confidence intervals (95% CI s) were calculated using logistic regression analysis. We identified 13 229 cases and 106 444 noncases. In the first 5 years after marketing, poor‐selectivity NSAID s and acetic acid derivatives were associated with the highest ROR of HSR s (age‐ and sex‐adjusted ROR 2.12, 95% CI 1.98–2.28; and ROR 2.21, 95% CI 1.83–2.66, respectively) compared with coxibs, and sulfonamide NSAID s were associated with the highest ROR of HSR s compared with nonsulfonamide NSAID s (age‐ and sex‐adjusted ROR 1.38, 95% CI 1.29–1.47). After the first 5 years of marketing, most of the ROR s returned to approximately 1.