Celecoxib (Celebrex™)
Meloxicam (Mobicox™)

General comments
Cyclooxygenase-2 Selective Inhibitors (COXIBs) are a new type of nonsteroidal anti-inflammatory agent. Unlike older NSAIDs, which block both COX isoforms, COXIBs selectively preserve the effects of COX-1 while at the same time selectively inhibiting the effects of COX-2. COX-1, a “constitutive” enzyme, is found in most tissues and is thought to protect the gastric mucosa and perform other so-called “housekeeping functions” in other tissues. COX-2 is “induced” at sites of inflammation and in other tissues, and is also found “constitutively” in the brain and kidney. Currently, celecoxib and meloxicam are the only COXIBs available in Canada.

Although COXIBs are indicated only for pain control in osteoarthritis (OA) or rheumatoid arthritis (RA), they may have similar efficacy as traditional NSAIDs for the treatment of regional pain syndromes, gout, pseudogout and seronegative arthritis, seronegative arthritis and polymyalgia rheumatica. COXIBs may be indicated for pain management and inflammation control in patients with acute or severe OA or RA. However, TYLENOL* (acetaminophen) still remains the first agent of choice for the management of mild-to-moderate OA pain because of its safety, effectiveness and cost.

The main benefit of COXIBs appears to be an improved gastrointestinal safety profile when compared with other NSAIDs. Studies have shown that the incidence of ulcers with COXIBs was lower when compared with naproxen and diclofenac. However other safety issues still need to be considered:

• Are COXIBs safe for use in patients with GI inflammation?
• Will COXIBs retard ulcer healing?
• Will COXIBs cause ulcers in those with a previous history of ulcers or those with gastric erosions?

At this point in time, data on these issues are either inconclusive or unpublished.

COXIBs have demonstrated a significant decrease in the occurrence of ulcers in prospective endoscopic studies compared with traditional NSAIDs. Ongoing studies will determine whether there is indeed a significant reduction in serious GI events including perforation, ulcer, bleeds and mortality.

COXIBs may be associated with side effects if the patient has pre-existing hypertension and/or fluid retention. Current information suggests that COXIBs may be associated with increased cardiorenal toxicity when compared with placebo and traditional NSAIDs. This includes increased rates of myocardial infarction. These concerns have resulted in the withdrawal of two popular COXIBs from the market, rofecoxib (Vioxx) and valdecoxib (Bextra). Future information is required to determine if COXIBs have more long-term vascular toxicities and how this might relate to similar, previously unexpected, side effects with traditional NSAIDs.

Indications

• Regional pain syndromes
• Degenerative joint disease (osteoarthritis [OA])
• Rheumatoid arthritis (RA)

Dosage of COXIBs varies according to clinical indication (pain management vs OA vs RA).

Dosage used in clinical practice
200 to 400 mg po daily (in single or divided doses)

Dosage according to CPS

• OA:
  • 200 mg od or bid
• RA:
  • Starting dose: 100 mg bid
  • Dose can be increased to 200 mg bid

Dosage used in clinical practice
7.5 to 15 mg po daily

• OA: 7.5 mg od; can be increased to 15 mg od
• RA: 15 mg od; can be reduced to 7.5 mg od