Celecoxib indications

Celecoxib is indicated for the treatment of osteoarthritis and rheumatoid arthritis. Its use is contraindicated in individuals with hypersensitivity to sulfonamides or other NSAIDs. It should be used with caution in persons with hepatic disease. Interactions occur with other drugs that induce CYP2C9 (e.g. ri-... 

Rofecoxib is approved for the treatment of acute pain and dysmenorrhea at a dose of 50 mg for up to 5 days. The clinical studies indicate that rofecoxib shows efficacy similar to that produced by the maximum analgesic doses of naproxen and ibuprofen (Ehrich et al., 1999). The pain settings in which rofecoxib has been tested include acute postoperative dental pain, the pain of dysmenorrhea for up to 3 days, and postoperative pain for 5 days following surgical replacement of the knee or hip. In contrast, celecoxib is not approved in the United States for the treatment of acute pain, and it appears to be less effective when given acutely than rofecoxib, ibuprofen, or naproxen. The explanation for the differences between rofecoxib and celecoxib in acute pain is not known. 

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. 

Ongoing research led to the development of COX-2 selective inhibitors (e.g., rofecoxib and celecoxib). Celecoxib (Celebrex ) was approved by the FDA in 1998 to treat osteoarthritis and rheumatoid arthritis. Rofecoxib (Vioxx ) was approved in May 1999 to treat osteoarthritis, acute pain, and dysmenorrhea. Sales for the two drugs in 1999 were 1.5 billion and 373 million, respectively. Clinical studies have indicated a significant reduction in GI perforation, ulceration, or bleeding with the COX-2 inhibitors. The recognition of multiple COX isoforms has had one of the greatest impacts on the development of NSAIDs since the original synthesis of aspirin more than a century ago. 

Experimental evidence indicates that COX modulates BBB permeability in neuroinflammatory conditions, ischemia, and hemorrhage. The COX inhibitor, KBT-3022, prevented brain edema induced by bilateral carotid occlusion and recirculation in gerbils (Yamamoto et al., 1996). In the collagenase model of intracerebral hemorrhage, the brain water content of rats treated with the COX-2 inhibitor, celecoxib, decreased both in lesioned and nonlesioned hemispheres in a dose-dependent manner, which was accompanied with reduced perihematomal cell death (Chu et al., 2004). Delayed damage to the BBB and vasogenic edema, which follow ischemic stroke, were significantly diminished by administration of... 

In the second analysis, data from 14 studies of the efficacy of celecoxib in osteoarthritis or rheumatoid arthritis in 11 007 patients were pooled (80,81). Gastrointestinal complications (bleeding, obstruction, or perforation) occurred in 0.2% of the patients per year of exposure to celecoxib and in 1.7% per year of exposure to traditional NSAIDs. The absolute risk reduction was 1.5% (Cl = 0.4, 2.6). This study, too, had some limitations. In fact, ulcer complication was not the specified end-point of the studies that were pooled, and about 15% of celecoxib-treated patients took a dose below that indicated for arthritis. 

Prostacyclin is increased in response to ischemia and reperfusion through activation of the cyclooxygenase-2 pathway. Inhibition of cyclooxygenase-2 by celecoxib or meloxicam resulted in a concentration dependent exacerbation of the myocardial dysfunction and damage in a perfused rabbit heart model of ischemia and reperfusion, indicating a cardioprotective role for prostacyclin.104... 

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. 

Celecoxib is a selective COX-2 inhibitor/GI agent that reduces inflammation (e.g., pain, redness, swelling, heat), fever, and pain by inhibiting chemicals in the body that cause inflammation, fever, and pain. This is probably caused by the inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2) isoenzyme. Celecoxib is indicated in relief of symptoms of osteoarthritis relief of symptoms of rheumatoid arthritis in adults management of acute pain in adults treatment of primary dysmenorrhea and reduction of the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP), as an adjunct to usual care (e.g., endoscopic surveillance, surgery). 

Celecoxib is currently indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis and to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib is at least as effective as naproxen in the symptomatic management of osteoarthritis and at least as effective as naproxen and diclofenac in the symptomatic treatment of rheumatoid arthritis, and it is less likely to cause adverse Gl effects. Celecoxib appears to be effective in the management of pain associated with both of these arthritic conditions, but effectiveness in acute or chronic pain has not been fully demonstrated. Unlike aspirin, celecoxib does not exhibit antiplatelet activity. Concomitant administration of aspirin and celecoxib may increase the incidence of Gl side effects. Another notable potential drug interaction with celecoxib is its ability, like other NSAIDs, to reduce the blood pressure response to angiotensin-converting enzyme inhibitors. A more detailed discussion of the chemical, pharmacological, pharmacokinetic, and clinical aspects of celecoxib is available (81). 

Some of the NSAIDs cited here have not been reported to interact (celecoxib, lumiracoxib, meloxicam, piroxicam), and information about some other NSAIDs seems to be lacking, but the same general precautions indicated above should be followed with all NSAIDs just to be on the safe side. 

COX-2 Inhibitors Induce Apoptosis with Considerable Differences in Potency. The apoptotic effects of a panel of COX-2-specific inhibitors on human prostate cancer cell lines were evaluated. Table 1 shows that the COX-2 inhibitors, NS398, DuP697, rofecoxib and celecoxib, are similar structurally and with respect to their potencies in COX-2 inhibition (79). In addition, as we reported previously for celecoxib (66), NS398, DuP697, and rofecoxib were capable of inducing apoptosis in both LNCaP and PC-3 cells, as indicated by the characteristic apoptotic features including DNA laddering and caspase-3 (EC 3.4.22.1) activation (Fig. IB and C only data for PC-3 cells is shown). Similarly,... 

Fig. 7. Susceptibility of prostate cancer cells to celecoxib-induced apoptosis is independent of cyclooxygenase-2 (COX-2) expression levels. (A, left panel) Effect of 50 pM celecoxib on the viability of parental PC-3 cells and the COX-2-deficient clone 2 F6. (A, right panel) Effect of 50 pM celecoxib on the viability of the COX-2 antisense clone 7D9 with (+) or without (-) a doxycycline (Dox) pretreatment (2 pg/mL). Data represent means 95% confidence intervals (error bars) (n = 3). (B) Effect of celecoxib on the phosphorylation status of Akt and extracellular signal regulated kinase (ERK)2 in the COX-2 antisense clone 7D9 with or without doxycycline treatment (2 pg/mL) as indicated. Western blots are representatives of three independent experiments. These data indicate that the mechanism underlying celecoxib-induced apoptotic death in the 7D9 cells remained unaltered after COX-2 depletion. Source Song, X., Lin, H.P., Johnson, A.J., Tseng, P.H., Yang, Y.T., Kulp, S.K., and Chen, C.S. (2002) Cyclooxygenase-2, Player or Spectator in Cyclooxygenase-2 Inhibitor-Induced Apoptosis in Prostate Cancer Cells, j. Natl. Cancer Inst. 94, 585-591 by permission of Oxford University Press.

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