Perforation naproxen

In the VIGOR study, 8076 patients with rheumatoid arthritis were randomly assigned to receive rofecoxib 50 mg/day or naproxen 500 mg bd. The primary endpoint was a confirmed clinical upper gastrointestinal event (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer). 

Overall, confirmed upper gastrointestinal events occurred in 177 patients, 56 with rofecoxib n — 4047), and 121 in those taking naproxen n — 4029). In 53 of these patients (16 taking rofecoxib and 37 taking naproxen) the event was complicated. That means that during a median follow-up of 9.0 months, there were 2.1 confirmed gastrointestinal events per 100 patient-years with rofecoxib compared with 4.5 per 100 patient-years with naproxen (RR = 0.5 95% Cl = 0.2, 0.8). The respective rates of complicated ulcers (perforation, obstruction, and bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (RR = 0.4 95% Cl = 0.2, 0.8). 

The risk of serious upper gastrointestinal bleeding was inereased by the use of more than one NSAID in a meta-analysis of data from three ease-eontrolled studies (odds ratio 4.9 with one NSAID and 10.7 with two). Another study provided similar findings the odds ratio was 7.1 with one NSAID and 12.3 with two or more NSAIDs. Similar findings have been reported with aspirin and NSAIDs, see NSAIDs + Aspirin Anti-inflammatory dose , p.l42. Analysis of yellow eard reports to the CSM in the UK, of gastrointestinal perforation, obstruetion, uleeration or bleeding with diclofenac, naproxen, and ibuprofen, revealed that 6% of the patients were reeeiving another non-aspirin NSAID. ... 

The ceiling effect of naproxen limits the amount of pain relief that can be expected. It may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. Enteric coated formulations are available to help reduce the risk of such complications. 

A lower gastrointestinal risk with coxibs was confirmed in a retrospective case-control study of the incidence of peptic ulcer bleeding and perforation in users of COX-2 selective and non-selective NSAIDs [3 ]. The study was based on 2.2 million adults taking celecoxib, diclofenac, ibuprofen, naproxen, rofecoxib, or valdecoxib. Adjusted odds ratios (OR) compared with naproxen were ibuprofen 0.86 (95% Cl = 0.68, 1.09), rofecoxib 0.79 (0.62, 1.02), diclofenac 0.66 (0.47, 0.94), valdecoxib 0.50 (0.26, 0.97), and celecoxib 0.45 (0.35, 0.58). The overall... 

NSAIDs, such as aspirin, IND, ketoprofen, ibuprofen, naproxen, sulindac and flurbiprofen, are widely used in treatment of chronic inflammatory diseases. Recent studies have also shown that they have activity in retardation of colonic tumor growth [89-91]. However, oral administration of NSAIDs usually generates gastrointestinal side effects (e.g. gastric ulcers and gastric perforation) [92]. Therefore, colon-specific and controlled release of NSAIDs are important to achieve sustained pharmacologic effects and reduce the side effects. 

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