New COX-2 inhibitor cleared for rheumatoid arthritis

December 10, 2001

Pharmacia's Bextra is approved for RA

 

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New COX-2 inhibitor cleared for rheumatoid arthritis

The Food & Drug Administration has approved a new COX-2 inhibitor for treating the signs and symptoms of osteoarthritis (OA), rheumatoid arthritis (RA), and the treatment of primary dysmenorrhea. Bextra (valdecoxib), made by Pharmacia Corp., will be promoted in partnership with Pfizer, according to Stephanie Fagan, Pharmacia's public relations manager. "It is the second drug to emerge from the Pharmacia/Pfizer COX-2 franchise. The first was celecoxib [Celebrex], the world's first COX-2 inhibitor," she said.

For the more than 23 million Americans with some form of arthritis, valdecoxib offers the advantage of once-daily dosing and a lower incidence of gastrointestinal complications, compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs), said Fagan. According to the American College of Rheumatology, OA is the most common form of arthritis, affecting 21 million Americans. Characterized by joint and adjacent bone degeneration, OA can cause pain and stiffness and is a chronic disorder. RA is an autoimmune disorder that affects joint lining, cartilage, and bones.

The recommended daily dose of valdecoxib for both OA and RA is 10 mg once daily, Pharmacia said. Clinical trials with valdecoxib 10 mg once daily have evaluated its efficacy compared with that of ibuprofen 800 mg three times daily, diclofenac 75 mg twice daily, and naproxen 500 mg twice daily for treating OA. Researchers have found valdecoxib to be comparable to all three traditional NSAIDs for treating the signs and symptoms of OA, according to Pharmacia. Valdecoxib 10 mg once daily was found to be as effective as naproxen 500 mg twice daily for treating RA, the company added.

Researchers have also found valdecoxib to be effective in treating menstrual pain. Two placebo-controlled trials evaluated the drug's efficacy in treating the signs and symptoms of dysmenorrhea. In each trial, valdecoxib 20 mg twice daily was compared with naproxen sodium 550 mg twice daily. The onset, intensity, and duration of analgesic effect of valdecoxib were comparable to naproxen sodium. "More than 80% of women in both trials responded to only one dose of valdecoxib 20 mg," Fagan said.

One of the major concerns with traditional NSAIDs is the risk for GI complications. "The promise of COX-2 technology allows for a lower incidence of GI adverse effects," Fagan noted. Researchers were able to determine this in trials comparing valdecoxib 10 mg once daily with placebo or naproxen 500 mg twice daily. They found that valdecoxib was significantly less likely to cause endoscopically detected gastroduodenal ulcerations. According to data on file at Pharmacia, the incidence of endoscopically detected gastroduodenal ulcerations associated with valdecoxib (3%) was similar to placebo (4%) and significantly lower compared with naproxen (10%) in one trial.

A six-month study of OA and RA patients evaluated the effects of valdecoxib 20 mg or 40 mg once daily on endoscopically detected gastroduodenal ulceration. The doses used were much higher than those for use in treating arthritis or dysmenorrhea, Pharmacia said. The rates were 4% and 8%, respectively, which were still significantly less than that seen with naproxen 500 mg twice daily (18%).

The good news is that valdecoxib appears to be well tolerated. "What this means is that valdecoxib offers the patient the advantage of efficacy equal to NSAIDs with a more tolerable GI safety profile," claimed Fagan. Its overall upper GI safety profile was significantly better than traditional NSAIDs in clinical trials. The most commonly reported adverse effects included dyspepsia, headache, abdominal pain, nausea, and diarrhea.

Pharmacia does state that, as with other COX-2 inhibitors and NSAIDs, valdecoxib should be used with caution in patients with fluid retention, hypertension, or heart failure. Controlled clinical trials in patients with arthritis have found that doses of 10 mg per day are not associated with an increased risk of cardiovascular and renal complications when compared with traditional NSAIDs.

Pharmacia has yet to establish the cost of valdecoxib. "Though its exact launch date has not been established, it is anticipated that valdecoxib will be released during the early part of 2002," Fagan said.

Elena Bablenis Haveles, Pharm.D.

The author is a clinical writer in Virginia.

TIPS TO REMEMBER: Bextra

  • Bextra can cause mild gastrointestinal discomfort (i.e., dyspepsia); there is also a potential for serious GI ulceration and bleeding, which could result in hospitalization.

  • Patients should be counseled on the signs and symptoms of GI ulceration and bleeding, such as dark, bloody, tarry stools; bruising; unusual or prolonged bleeding; and coffee ground vomit.

  • Patients should report any of the following: skin rash, weight gain, and edema; patients should also report signs of hepatotoxicity, such as nausea, fatigue, lethargy, jaundice, pruritus, right upper quadrant tenderness, and flu-like symptoms

  • Patients should seek medical attention in case of an anaphylactic-like reaction.

  • Patients with a history of asthma or other allergic reactions following aspirin, nonsteroidal anti-inflammatory drug, or COX-2 inhibitor ingestion should not take Bextra.

  • Bextra should not be used in women during late pregnancy because it may cause premature closure of the ductus arteriosus.

 

Elena Haveles. New COX-2 inhibitor cleared for rheumatoid arthritis. Drug Topics 2001;23:14.