What about Celebrex (Celecoxib)?

From the Guidelines

Celebrex (Celecoxib) significantly increases the risk of cardiovascular events in a dose-dependent manner.

Key Points

• The American Heart Association has warned about the increased risk of cardiovascular events with COX-2 inhibitors, including Celebrex 1.
• The risk of cardiovascular events with Celebrex is dose-dependent, with higher doses (400 mg twice daily) associated with a statistically significant risk of stroke, MI, sudden cardiac death, and congestive heart failure 1.
• However, at typical doses used for pain or arthritis, the risk of cardiovascular events with Celebrex may be lower than with other NSAIDs, such as naproxen and indomethacin 1.
• The FDA has recommended that physicians consider alternative therapy or use the smallest effective dose of Celebrex, and has added a "black box" warning to the labeling 1.

Important Considerations

• Patients at high risk of gastrointestinal bleeding or with a history of intolerance to nonselective NSAIDs may be appropriate candidates for COX-2 selective agents like Celebrex 1.
• Individual patient risk for cardiovascular events and other risks commonly associated with NSAIDs should be taken into account for each prescribing situation 1.
• Further research is needed to fully characterize the risks associated with specific COX-2 inhibitors and nonselective NSAIDs, and to determine the best approach to weighing cardiovascular and GI risks in patients requiring anti-inflammatory analgesia 1.

From the FDA Drug Label

Celecoxib capsules has demonstrated significant reduction in joint pain compared to placebo. Celecoxib capsules was evaluated for treatment of the signs and the symptoms of OA of the knee and hip in placebo- and active-controlled clinical trials of up to 12 weeks duration In patients with OA, treatment with celecoxib capsules 100 mg twice daily or 200 mg once daily resulted in improvement in WOMAC (Western Ontario and McMaster Universities) osteoarthritis index, a composite of pain, stiffness, and functional measures in OA A total daily dose of 200 mg has been shown to be equally effective whether administered as 100 mg twice daily or 200 mg once daily. Celecoxib capsules has demonstrated significant reduction in joint tenderness/pain and joint swelling compared to placebo. Celecoxib capsules was shown to be superior to placebo in these studies, using the ACR20 Responder Index, a composite of clinical, laboratory, and functional measures in RA. Celecoxib capsules doses of 100 mg twice daily and 200 mg twice daily were similar in effectiveness and both were comparable to naproxen 500 mg twice daily Although celecoxib capsules 100 mg twice daily and 200 mg twice daily provided similar overall effectiveness, some patients derived additional benefit from the 200 mg twice daily dose. Doses of 400 mg twice daily provided no additional benefit above that seen with 100 mg to 200 mg twice daily.

Celebrex (Celecoxib) is used to treat osteoarthritis (OA) and rheumatoid arthritis (RA). The recommended doses are 100 mg twice daily or 200 mg once daily for OA, and 100 mg twice daily or 200 mg twice daily for RA. Some patients may derive additional benefit from the 200 mg twice daily dose. However, doses of 400 mg twice daily provided no additional benefit above that seen with 100 mg to 200 mg twice daily 2.

From the Research

Overview of Celebrex (Celecoxib)

• Celecoxib, also known as Celebrex, is a cyclo-oxygenase (COX) 2-selective inhibitor used for the relief of the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), juvenile rheumatoid arthritis, and ankylosing spondylitis 3.
• It is also approved for the management of acute pain in adults, the treatment of primary dysmenorrhoea, and the reduction in the number of adenomatous colorectal polyps in familial adenomatous polyposis 3.

Efficacy and Safety

• Celecoxib has been shown to be significantly superior in efficacy to placebo and similar in efficacy to traditional non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of OA and RA 4, 5.
• The gastrointestinal (GI) safety profile of celecoxib is superior to that of traditional NSAIDs and similar to that of placebo 4, 6.
• The renal and cardiovascular safety of celecoxib has also been demonstrated, as well as its efficacy, tolerability, and safety in the elderly population 4, 6.
• However, the potential GI, cardiovascular, and renal risks of celecoxib must be weighed against the potential benefits in each individual 3, 6.

Comparison to Other NSAIDs

• Celecoxib has been shown to be as effective as nonselective NSAIDs and other coxibs, such as etoricoxib and lumiracoxib, for the symptomatic treatment of patients with active OA, RA, or ankylosing spondylitis 6.
• The incidence of upper GI ulcer complications with recommended dosages of celecoxib is significantly lower than that with nonselective NSAIDs and similar to that with paracetamol and other coxibs 6.
• However, concomitant administration of celecoxib with low-dose cardioprotective aspirin may negate the GI-sparing advantages of celecoxib over NSAIDs 6.

Special Considerations

• Celecoxib may be a useful option for therapy in patients at high risk for NSAID-induced GI toxicity, or in those responding suboptimally to or intolerant of NSAIDs 3, 6.
• Older patients may gain significant benefits from celecoxib compared to traditional NSAIDs due to reduced gastrointestinal events, even with a history of ulcer bleedings 5.
• However, there is still limited knowledge regarding the prescription of celecoxib in patients with cardiovascular co-morbidities, and low doses seem to be safe according to present data 5.