Tidsskr Nor Laegeforen. 2002 Feb 20;122(5):476-80.  Related Articles, Links

[A critical evaluation of side effect data on COX-2 inhibitors]

[Article in Norwegian]

Pomp E.

Regionalt Legemiddelinformasjonssenter Haukeland Sykehus 5021 Bergen. erik.pomp@haukeland.no

BACKGROUND: Celecoxib and rofecoxib have been used in Norway since 2000. These cyclooxygenase 2 inhibitors (COX-2 inhibitors) have no better clinical efficacy than older non-steroid anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis or osteoarthritis, but may possibly lead to a lower incidence of upper gastrointestinal ulcers. MATERIAL AND METHODS: Published and unpublished clinical data on side effects were examined and interpreted. The aim was to evaluate the general safety of these new drugs compared with older NSAIDs. RESULTS: The incidence of side effects is addressed in two large published studies comparing COX-2 inhibitors with other NSAIDs. Only rofecoxib showed an unequivocal lower incidence of complicated upper gastrointestinal ulcers. However, the incidence of serious side effects was significantly higher in the rofecoxib group. In the other study there was a trend towards more serious side effects in the celecoxib group. INTERPRETATION: The available clinical data do not suggest that COX-2 inhibitors are safer drugs than other NSAIDs.

Publication Types:

Review

Review, Tutorial

PMID: 11961974 [PubMed - indexed for MEDLINE]

Rev Med Brux. 2001 Sep;22(4):A377-80.  Related Articles, Links

[COX-2 inhibitor non-steroidal anti-inflammatory drugs, myth or reality?]

[Article in French]

Peretz A.

Clinique de Rhumatologie, Departement de Medecine Interne, C.H.U. Brugmann, U.L.B.

The discovery of two isoforms of cyclooxygenase, Cox-1 constitutive and Cox-2 inducible, has prompted the development of new molecules with high Cox-2 selectivity. These new NSAIDs belong to the coxib class and have theoretically a better digestive tolerability than classical NSAID have. In Belgium, rofecoxib ((Vioxx) and celecoxib (Celebrex) are commercialized. Rofecoxib is indicated in the symptomatic treatment of osteoarthritis (12.5 to 25 mg/d) and celecoxib is indicated in osteoarthritis (200 mg/d) and in rheumatoid arthritis (200 to 400 mg/d). Several studies have demonstrated their efficacy, similarly to classical NSAID as diclofenac (Voltaren), naproxen (Naprosyne), ibuprofen (Brufen) and their superiority compared to placebo. Their safety profile for gastrointestinal events is proven in patients without ulcer history compared to classical NSAID. However, the concomitant use of aspirin decreases the benefit as demonstrated for celecoxib at 400 mg/d but not investigated for rofecoxib. The selective inhibition of Cox-2 with no effect on Cox-1 favors cardiovascular events in patients at risk. Other side effects are similar to classical NSAID. Thus Cox-2 inhibitors NSAID are interesting molecules for their sparing gastrointestinal activity. They must be used with caution in patients with ulcer history, in the elderly and in patients requiring aspirin for cardiovascular prophylaxis.

Publication Types:

Review

Review, Tutorial

PMID: 11680204 [PubMed - indexed for MEDLINE]

1: Drug Ther Bull.  2000 Nov;38(11):81-6.

Are rofecoxib and celecoxib safer NSAIDS?

[No authors listed]

NSAIDs work by inhibiting the enzyme cyclo-oxygenase (COX), responsible for

prostaglandin synthesis. This enzyme exists in two isoforms, COX-1 and COX-2.

Inhibition of COX-1 is thought to be the main cause of the gastrointestinal

unwanted effects of NSAIDs, whilst inhibition of COX-2 results in

anti-inflammatory effects. [symbol: see text]Rofecoxib (Vioxx--MSD) and [symbol:

see text]celecoxib (Celebrex--Searle) have been developed as selective

inhibitors of COX-2. Rofecoxib is licensed for the symptomatic treatment of

osteoarthritis, but not for rheumatoid arthritis. The manufacturer claims that

"in clinical studies rofecoxib inhibits COX-2 but not COX-1", has "the power of

high-dose NSAIDs--diclofenac and ibuprofen" and "superior GI safety profile

compared to conventional NSAIDs". Celecoxib is licensed for symptom relief in

osteoarthritis and rheumatoid arthritis. The manufacturer claims that celecoxib

has "comparable efficacy and superior GI tolerability when compared to

diclofenac or naproxen". Here, we review rofecoxib and celecoxib and consider

whether they are safer than conventional NSAIDs.

Publication Types:

Review

Review, Tutorial

PMID: 11138599 [PubMed - indexed for MEDLINE]

Am J Med. 2001 Feb 19;110 Suppl 3A:13S-9S.  Related Articles, Links

Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors.

Buttgereit F, Burmester GR, Simon LS.

Department of Rheumatology and Clinical Immunology, Charite University Hospital, Humboldt University, (FB, GRB), Berlin, Germany. frank.buttgereit@charite.de

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation but are frequently associated with gastrointestinal side effects, including life-threatening bleeding or perforation of gastroduodenal ulcers. Conventional NSAIDs are nonselective inhibitors of two isoforms of cyclooxygenase (COX): COX-1 and COX-2. The inhibition of COX-1 is believed to be responsible for inducing mucosal injury primarily by impairing prostaglandin-dependent mucosal protective mechanisms. The latest development in reducing the incidence of ulcers and ulcer complications associated with conventional NSAIDs is the use of recently approved COX-2-specific inhibitors (CSIs). This article critically reviews the data on gastrointestinal toxic side effects for conventional NSAIDs without as well as with prevention therapy. In addition, we compare these data with those for the CSIs, namely, celecoxib and rofecoxib. Finally, we offer recommendations on the clinical use of these drugs, emphasizing the need to balance clinical effectiveness with the avoidance of potential gastrointestinal side effects.

Publication Types:

Review

Review, Tutorial

PMID: 11173045 [PubMed - indexed for MEDLINE]