Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature

Abstract

Adverse events triggered by non-steroidal antiinXammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966MEDLINE ( -2006, the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966EMBASE ( -2006 up to December 9, 2006, and analysed all publications included using a predeWned evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/ 56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inXammation is advantageous.

Nonallergic Drug Hypersensitivity Reactions

“…COX-2 inhibitors can be safely given to AERD patients based on several trials in which patients with AERD were challenged with COX-2 inhibitors [100,101,102,103]. However, there have been case reports of AERD patients reacting to COX-2 inhibitors [104,105]. The mechanism of COX-2-related AERD is unknown and it may be prudent in patients with known AERD to perform an oral provocation test with the COX-2 under close observation before recommending its use [106].…”

Agents that induce pseudo-allergic reaction

“…Pseudo-allergic reactions to NSAIDs account for 21% to 25% of all adverse drug reactions (91). Taking aspirin as an example, intolerance reactions are typically developed with the symptoms of rhinorrhea and conjunctival irritation within one hour after aspirin administration with acute asthma attacks (92).…”

The selective COX-2 inhibitor Etoricoxib reduces acute inflammatory markers in a model of neurogenic laryngitis but loses its efficacy with prolonged treatment

“…Classical NSAIDs are the most commonly used drugs for the treatment of pain and inflammation in a wide range of diseases, including ear, nose and throat conditions [21][22][23]. These drugs act primarily by blocking the synthesis of prostaglandins by cyclooxygenase (COX) enzymes [13,21].…”

“…These drugs act primarily by blocking the synthesis of prostaglandins by cyclooxygenase (COX) enzymes [13,21]. Their therapeutic effects are related to the inhibition of inflammation-induced COX-2, whereas their most common side effects are related to the inhibition of the constitutive COX-1 enzyme [21,24,25]. Interestingly, aerodigestive and cutaneous adverse events related to the use of NSAIDs are known to be one of the most common in medicine [21].…”

“…Contrarily to the classical NSAIDs that inhibit both isoforms of COX enzymes, the selective COX-2 inhibitors like Etoricoxib, mainly block the activity of the inducible COX-2 enzyme [13,14,21,24,25]. This may result in a better tolerability profile, with less associated side effects.…”