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

Adverse events triggered by non-steroidal anti-inflammatory 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 (1966-2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966-2006) up to December 9, 2006, and analysed all publications included using a predefined 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 inflammation is advantageous.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Interventions for pain during fixed orthodontic appliance therapy: a systematic review

OBJECTIVE: To compare the different methods of pain control intervention during fixed orthodontic appliance therapy.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain

BACKGROUND: We have reviewed the analgesic efficacy of cyclooxygenase-2 (COX-2) inhibitors compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs), different COX-2 inhibitors, and placebo in post-operative pain.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2004

Systematic review of the analgesic efficacy and tolerability of COX-2 inhibitors in post-operative pain control

OBJECTIVE: To evaluate the relative analgesic efficacy and tolerability of single-dose COX-2 inhibitors in post-operative pain management.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2004

Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the reduction of morphine-related side effects after major surgery: a systematic review

OBJECTIVES: To determine which class of non-opioid analgesics - paracetamol (acetaminophen), NSAIDs or COX-2 inhibitors - is the most effective at reducing morphine consumption and associated adverse effects when used as part of multimodal analgesia following major surgery.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2010

Cyclooxygenase-2 inhibitors in postoperative pain management: current evidence and future directions

This review assessed the use of cyclooxygenase-2 (COX-2) inhibitors for pain following surgery. In terms of pain reduction and side-effects, the authors concluded that COX-2 inhibitors are similar to non-steroidal anti-inflammatory drugs. The review does not give enough information to enable a confident judgement about how reliable or generalisable the conclusion is.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2003

Relative thromboembolic risks associated with COX-2 inhibitors

This review found that celecoxib was the safest cyclooxygenase-2 inhibitor when given in the lowest possible dose. The limited search, inadequate reporting of review methods, lack of a quality assessment of the included studies, and reliance upon data from observational studies to compare drugs mean that any conclusions might not be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2005

Risk of myocardial infarction associated with selective COX-2 inhibitors: meta-analysis of randomised controlled trials

The authors concluded that selective cyclooxygenase-2 inhibitors (coxibs) were associated with a significantly increased risk of myocardial infarction compared with placebo and non-selective non-steroidal anti-inflammatory drugs (NSAIDs); the risk of myocardial infarction differed between coxibs and individual NSAIDs. The data appear to support the conclusions, but it is difficult to assess their reliability given the limitations in reporting of review methodology.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2007

Frankincense: systematic review

The author concluded that Boswellia serrata extracts appear to be effective in treating a range of conditions caused or maintained by inflammatory processes. However, the evidence is encouraging rather than convincing and further research is warranted. Apart from some limitations in the methods, this was a well-conducted review and the author's conclusions are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2008

Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients

This review assessed the hepatic side-effects of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with arthritis. The authors concluded that NSAIDs did not increase liver-related serious adverse effects, hospitalisation or death, but diclofenac and rofecoxib increased aminotransferase elevations compared with placebo and other NSAIDs examined. The conclusions were drawn from indirect comparisons, hence they may not be robust.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2005

Coxibs versus combination NSAID and PPI therapy for chronic pain: an exploration of the risks, benefits, and costs

This review compared cyclooxygenase-2 inhibitors (coxibs) with non-selective non-steroidal anti-inflammatory drugs plus a proton-pump inhibitor for patients with chronic musculoskeletal pain. The authors concluded that coxibs provide comparable pain control and produce fewer gastrointestinal complications, although the risk of cardiovascular events is unknown. The presence of several methodological flaws in the review process mean that the reliability of these conclusions is unclear.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2006

Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies

The authors' reasonably cautious conclusion that naproxen and ibuprofen have the most favourable cardiovascular risk profiles is likely to be reliable, but should be weighted against other risks when making clinical decisions.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2011

Do selective COX-2 inhibitors increase the risk of cerebrovascular events: a meta-analysis of randomized controlled trials

The review concluded that there was no evidence of a significantly increased risk of cerebrovascular events associated with selective cyclooxygenase-2 inhibitors compared with placebo or or active treatment such as non-steroidal anti-inflammatory drugs. The authors’ conclusions are appropriate, given the evidence presented, and are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2006

Do COX-2 inhibitors raise blood pressure more than nonselective NSAIDs and placebo? An updated meta-analysis

This review found higher risks of hypertension associated with use of cyclo-oxygenase (COX-2) inhibitors compared with placebo and non-steroidal anti-inflammatory drugs (NSAID). Methodological flaws and a lack of information about the quality of the included studies mean that the results should be interpreted with a substantial degree of caution.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2009

Reduction of opioid-related adverse events using opioid-sparing analgesia with COX-2 inhibitors lacks documentation: a systematic review

This review evaluated opioid-related adverse events in studies of opioid sparing with cyclooxygenase-2 (COX-2) inhibitors compared with placebo in post-operative pain. The authors concluded that opioid sparing with COX-2 inhibitors does not have a clinically beneficial effect on opioid-related adverse events. The conclusion appears reliable based on the data presented, although relevant studies might not have been included.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2005

Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials

This review concluded that the vascular risks with high-dose diclofenac, and possibly ibuprofen, were comparable to those with cyclooxygenase-2 inhibitors, but they were less with high-dose naproxen. The size of these risks could be predicted. The review appears to have been well conducted, and the authors' conclusions are likely to be reliable.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials

The review assessed the analgesic efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with osteoarthritis of the knee. The authors concluded that NSAIDs reduce short-term pain slightly better than placebo, but evidence on long-term use is lacking. The conclusion appears to be appropriate given the evidence presented, although there were limitations in the reporting of the review process.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2004

Effect of preoperative Cox-II-selective NSAIDs (coxibs) on postoperative outcomes: a systematic review of randomized studies

This review evaluated the effect of pre-operative cyclooxygenase-2 (Cox-2) inhibitors on post-operative pain, adverse events and other reported outcomes. Cox-2 inhibitors were found to have benefits in terms of reduced post-operative pain and analgesic consumption in comparison with placebo. Although the conservative conclusions reflect the evidence presented, poor reporting of the review methods makes it difficult to assess their reliability.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2005

The role of COX-2 inhibitors in the perioperative setting: efficacy and safety. A systematic review

The author concluded that selective cyclooxygenase-2 inhibitors may be effective in the peri-operative management of carefully selected patients. The review appears to support the author's conclusion, but the limited search and poor reporting of the review methods, quality assessment and results data mean it is difficult to assess the reliability of these conclusions.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2006

Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis: meta-analysis of randomised trials

This review determined the effect of selective cyclo-oxygenase-2 (COX-2) inhibitors and traditional non-steroidal anti-inflammatory drugs on the risk of vascular events. The authors concluded that selective COX-2 inhibitors are associated with a moderate increase in the risk of vascular events. The lack of detail makes it difficult to judge the extent to which variation between the studies impacted upon the results.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2006

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