Celecoxib toxicity

Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis The CLASS study A randomized, controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000 284 1247-1255. 

Selective COX-2 inhibitors are ideal agents to combine with chemoradiotherapy for several reasons. First, they have been shown to enhance the effect of various chemotherapeutic agents and radiation on cancer cells. Second, selective COX-2 inhibitors are relatively safe. They do not have severe gastrointestinal toxicity, which is common in many nonselective NSAIDs. For example, celecoxib, a selective COX-2 inhibitor which is currently being used for patients with arthritis, is 375-fold more selective for COX-2 compared to COX-1 (94), and in large randomized, multicenter, placebo-controlled, double-blind trials conducted in patients with rheumatoid arthritis, celecoxib proved to be less toxic than nonselective inhibitors of COX-1 and COX-2, and no more toxic than a placebo (95). Third, high-dose celecoxib (600 mg bid) has no effect on serum thromboxane or platelet function (96). This is obviously important in patients receiving... 

Celecoxib Reversible COX-2 in- 8-12 (refers 5 NSAID with low toxicity and... 

Celecoxib (Celebrex) and rofecoxib (Vioxx) are highly selective COX-2 inhibitors. Because of this, they produce less erosion of the GI mucosa and cause less inhibition of platelet aggregation than do the nonselective COX inhibitors. Short-term (6 months-to a year) clinical trials have shown that celecoxib and rofecoxib produce less GI toxicity than nonselective NSAIDs. However, serious GI bleeding and ulceration have occurred in patients taking these drugs, and long-term prospective studies of their safety have yet to be completed. Like the nonselective NSAIDs, the selective COX-2 inhibitors can produce renal side effects such as hypertension and edema. 

Celecoxib is associated with fewer endoscopic ulcers than most other NSAIDs. Probably because it is a sulfonamide, celecoxib may cause rashes. It does not affect platelet aggregation at usual doses. It interacts occasionally with warfarin—as would be expected of a drug metabolized via CYP2C9. Adverse effects are the common toxicities listed above. 

K. M. Verburg, and G. S. Geis. 2000. Gastrointestinal Toxicity with Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis The CLASS Study A Randomized Controlled Trial. JAMA 284 1247-1255. 

Gunja N, Graudins A, Dowsett R. Lithium toxicity a potential interaction with celecoxib. Intern Med J 2002 32(9-10) 494. 

NSAIDs - CELECOXIB DRUG DEPENDENCE THERAPIES-BUPROPION t plasma concentrations of these substrates, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs at the lowest effective dose... 

Antifungal fluconazole raises the plasma concentration of, and thus risk of toxicity from, celecoxib. 

Selective inhibition of COX-2 has the objective of preserving anti-inflammatory activity whilst avoiding gastric mucosal toxicity. Rofecoxib, celecoxib and meloxicam vary in their selectivity for COX-2. The incidence of peptic ulcers and their complications with rofecoxib is similar to that seen when proton pump inhibitors are co-administered with nonselective NSAIDs. The adverse effect profile of these drugs remains fully to be evaluated. 

In conclusion, clinical trials have shown that COX-2-selective NSAIDs seem to be less toxic to the gastrointestinal mucosa than traditional ones. However, life-threatening ulcer complications have been reported in patients taking both celecoxib (81,96,97) and rofe-coxib (79). The FDA and other regulatory authorities require that drug information sheets for celecoxib and rofecoxib carry gastrointestinal ulcer warnings similar to those for older NSAIDs. 

There have been reports of maculopapular rash (117) and severe erythema multiforme (toxic epidermal necrolysis) (118) with celecoxib. Three patients developed erythema multiforme while taking rofecoxib (119). All were well documented, and oral rechallenge with rofecoxib, positive in two of them, confirmed the role of rofecoxib in the pathogenesis of this adverse reaction. 

Berger P, Dwyer D, Corallo CE. Toxic epidermal necrolysis after celecoxib therapy. Pharmacotherapy 2002 22(9) 1193-5. 

Celecoxib 1.34 (1.19-1.52) Naproxen 1.35 (0.97-1.88) Ibuprofen 1.51 (0.95-2.41) Acetaminophen 1.29 (1.17-1.42) Naproxen is associated with the highest risk of AMI/GI events in those not taking aspirin. Celecoxib and acetaminophen AMI/GI risk is similar and less than the other NSAIDs (selective and non-selective). Celecoxib and naproxen are the least toxic in comparison to the other NSAIDs in those using aspirin. 

Note Celecoxib is a sulfonamide and can be absorbed systemically. Sulfonamides can produce severe, possibly fatal, reactions such as toxic epidermal necrolysis and Stevens-Johnson syndrome... 

In summary, there is evidence that COX-2 inhibitors pose a decreased risk of GI toxicity compared to nonspecific NSAIDs, an especially important consideration when treating those at risk for clinically significant GI adverse effects. Rofecoxib decreases the extent of clinically significant GI complications. Celecoxib likely decreases these events, although the proof is less rigorous and still debated. For valdecoxib, its effect on clinically significant GI events awaits further study. 

Other toxic effects of NSAIDs include hypersensitivity reactions, rash, and central nervous system complaints of drowsiness, dizziness, headaches, depression, confusion, and tinnitus. Although NSAIDs are generally avoided in patients with asthma who are aspirin-intolerant, studies indicate that celecoxib and rofecoxib are well tolerated in aspirin-sensitive asthma, providing a viable option for these patients. Celecoxib and valdecoxib are sulfonamides and are thus contraindicated for those with sulfa allergies. 

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