Celecoxib adverse effects

COX-2 inhibitors such as celecoxib are associated with adverse effects such as nephrotoxicity and a potential increased risk of myocardial infarction (see Chaps. 55 and 15 for additional information). Combination of COX-2 inhibitors with alcohol may increase GI adverse effects. All NSAIDs should be used with caution in patients with aspirin-induced asthma.31... 

Meloxicam (Mobic), recently introduced for the treatment of osteoarthritis, is also used for rheumatoid arthritis and certain acute conditions. Although meloxicam is sometimes reported to be a selective COX-2 inhibitor, it is considerably less selective than celecoxib or rofecoxib. Its adverse effects are similar to those of piroxicam and other NSAIDs however, the frequency of GI side effects is lower for meloxicam than for piroxicam and several other NSAIDs. 

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. 

Meloxicam is an enolcarboxamide related to piroxicam that preferentially inhibits COX-2 over COX-1, particularly at its lowest therapeutic dose of 7.5 mg/d. It is not as selective as celecoxib and may be considered "preferentially" selective rather than "highly" selective. The drug is popular in Europe and many other countries for the treatment of most rheumatic diseases and approved for treatment of osteoarthritis in the USA. It is associated with fewer clinical gastrointestinal symptoms and complications than piroxicam, diclofenac, and naproxen. Similarly, while meloxicam is known to inhibit synthesis of thromboxane A2, even at supratherapeutic doses its blockade of thromboxane A2 does not reach levels that result in decreased in vivo platelet function (see common adverse effects above). 

The CLASS study published in fAMA in 2000 appeared to confirm the gastrointestinal protective effects of celecoxib (Celebrex ) over traditional NSAIDs after six months of treatment (Silverstein et al. 2000). However, material on the website of the FDA revealed a number of discrepancies between the data as published in fAMA and those submitted to the FDA. The published trial actually combined the results of two trials, one that continued for twelve months and the second which ran for 16 months. At 12-16 months there was no difference in gastrointestinal adverse effects between the celecoxib and traditional NSAID groups (Hrachovec and Mora 2001 Wright et al. 2001). 

The coxibs continue to be investigated to determine whether their effect on prostacyclin production could lead to a prothrombotic state. The frequency of other adverse effects approximates that of other NSAIDs. Celecoxib causes no more edema or renal effects than other members of the NSAID group, but edema and hypertension have been documented. 

Rheumatoid arthritis is a disease that involves inflammation in joints and causes severe pain and immobility. The worldwide scenario indicates that the elderly population suffers the most from this disease. The drugs of choice for treatment of this condition are nonsteroidal antiinflammatory drugs (NSAIDs), which include acetylsalicylic acid, diclofenac sodium, piroxicam, nimesulide, celecoxib, and refecoxib. Therapeutic doses, adverse effects, and precautions are given in the foifowing pages. 

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. 

The incidence of adverse effects related to renal function in CLASS and VIGOR was low and similar (0.9% with celecoxib and 1.2% with rofecoxib). The incidence of increased creatinine and urea nitrogen concentrations was slightly lower in patients taking celecoxib than in those taking ibuprofen or diclofenac. Similar results have been documented in two other clinical trials. The... 

Aside from consideration of the relatively uncommon but serious GI adverse effects described above, fewer overall GI complaints from patients are found for COX-2 inhibitors compared to nonspecific NSAIDs. Moreover, celecoxib use was associated with decreased outpatient physician claims for upper GI symptoms compared with other prescription nonspecific NSAIDs. Finally, celecoxib was comparable to a combination of diclofenac and misoprostol in reducing the risk of recurrent GI bleeding in patients who had a prior GI bleed. ... 

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. 

In the recent 8000-patient celecoxib long-term arthritis safety study [123], significantly more patients receiving traditional NSAlDs (ibuprofen or diclofenac) experienced clinically significant elevations in serum creatinine and/or serum urea nitrogen levels when compared to celecoxib. In an equally large gastrointestinal safety trial with rofecoxib, the incidence of adverse effects related to renal function for rofecoxib was similar to naproxen (1.2% versus 0.9%, respectively) [124]. When rofecoxib and celecoxib were directly evaluated in elderly hypertensive OA patients who manifested "normal" serum creatinine at the time of study recruitment, the overall incidence of clinically... 

Three members of the initial class of COX-2 inhibitors, coxibs, were approved for use in the United States and Europe. Both rofecoxib and valdecoxib have now been withdrawn from the market in view of their adverse event profiles. Two others, parecoxib and etoricoxib, are approved in Europe but still under consideration in the United States. The newest drug in the class, lumiracoxib, is under consideration for approval in Europe and the United States. The relative degree of selectivity for COX-2 inhibition is lumiracoxib = etoricoxib > valdecoxib = rofecoxib celecoxib. However, there is considerable difference in response to the coxibs among individuals, and it is not known how the degree of selectivity may relate to either efficacy or adverse effect profile, although it seems likely to be related to both. No controlled clinical trials comparing outcomes among the coxibs have been performed. 

Does celecoxib have adverse effects on the gastric mucosa ... 

NSAIDs block the activity of both isoforms. These findings have provided the impetns for the development of selective COX-2 inhibitors, which are proposed to act as potent anti-inflammatory agents by inhibiting COX-2 activity, withont the gastrointestinal and anti-platelet side effects commonly associated with NS AID use. These NS AID adverse effects are thought to be a result of COX-1 inhibition. Examples of these newer selective COX-2 inhibitors are celecoxib (Celebrex) and rofecoxib (Vioxx). 

Parecoxib had no effect on the pharmacokinetics of alfentanil or fentanyl, and celecoxib and rofecoxib appeared not to affect the pharmacokinetics of tramadol Coxibs can reduce the perioperative opioid requirement, but adverse effects are not necessarily reduced. 

Celecoxib does not demonstrate any adverse effects on bone healing in clinical trials [1 ]. 

Pregabalin and celecoxib, alone and in combination, have been evaluated in the treatment of chronic low-back pain in 36 patients in a 12-week, randomized, crossover study [267 ]. The combination was more effective than either monotherapy. Adverse effects were recorded in 16 patients and four patients withdrew as a result. Five patients reported nausea or dizziness during treatment with pregabalin and seven had similar symptoms during treatment with celecoxib -I- pregabalin. 

The anti-inflammatory effects of the NSAIDs are carried out by inhibition of COX-2. The gastrointestinal adverse reactions are caused by inhibition of COX-1. The newer NSAIDs (celecoxib and rofecoxib) appear to work by specifically inhibiting the COX-2 enzyme, without inhibiting the COX-1 enzyme. Celecoxib and rofecoxib relieve pain and inflammation with less potential for gastrointestinal adverse... 

Recent data suggest that COX-2 inhibitors, including rofe-coxib, valdecoxib, and celecoxib, may increase the risk for MI and stroke.47 There is also some evidence that the non-selective NSAIDs may increase the risk for cardiovascular events.47,48 Rofecoxib was withdrawn from the market in late 2004 because of safety concerns. The FDA requested the withdrawal of valdecoxib from the market in 2005. The FDA also asked the manufacturers of celecoxib and non-selective NSAIDs (prescription and over-the-counter) to include information about the potential adverse cardiovascular effects of these drugs in their product labeling. The cardiovascular risk with COX-2 inhibitors and NSAIDs may be greatest in patients with a history of, or with risk factors for, cardiovascular disease. The American Heart Association recommends that the use of COX-2 inhibitors be limited to low-dose, short-term therapy in patients for whom there is no appropriate alternative.48 Patients with cardiovascular disease should consult a clinician before using over-the-counter NSAIDs. 

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