Do Not Use! New Safety Warning Added to the Arthritis Drug Valdecoxib (BEXTRA)

In the Companion to the 1999 edition of Worst Pills, Best Pills we listed valdecoxib (BEXTRA), a new nonsteroidal anti-inflammatory drug (NSAID), as DO NOT USE because it is nothing more than an overpriced “me-too” product that is no safer and probably less effective than older NSAIDs such as ibuprofen (MOTRIN) or naproxen (NAPROSYN). Valdecoxib is chemically similar to another heavily promoted copycat NSAID celecoxib (CELEBREX), also a DO NOT USE drug (see Worst Pills, Best Pills News article April 2001).

Both valdecoxib and celecoxib are co-promoted by the pharmaceutical giants Pfizer Inc. and the Pharmacia Corporation.

There is an additional similarity between valdecoxib and celecoxib, both are sulfa drugs and individuals who are allergic to sulfa drugs should not use them. Although celecoxib came on the market with a warning about sulfa drug allergy, valdecoxib did not. In the Companion we wrote “It may be a dangerous oversight on the part of the FDA not to have required the same warning for valdecoxib.” Unfortunately, because uninformed patients have been needlessly harmed, our prediction has come to pass.

On November 13, 2002, Pfizer and Pharmacia notified healthcare professionals that the FDA required new warnings in the professional product information, or “package insert,” for valdecoxib. These include:

• “BEXTRA should not be given to patients who have demonstrated allergic type reactions to sulfonamides.”
• “Serious Skin Reactions: Serious skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported through postmarketing surveillance in patients receiving BEXTRA. As these reactions can be life threatening, BEXTRA should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.”
• “Anaphylactoid Reactions: In postmarketing experience, cases of hypersensitivity reactions (anaphylactic reactions and angioedema) have been reported in patients receiving BEXTRA. These cases have occurred in patients with and without a history of allergic-type reactions to sulfonamides."

The tragedy in this saga is that an undergraduate pharmacy student looking at the chemical structures of valdecoxib and celecoxib would have recognized that both are sulfa drugs.

Valdecoxib's manufacturer filed its application for the drug's marketing approval with the FDA in March 2001 asking that it be cleared for the treatment of acute pain, painful menstrual periods, and osteo- and rheumatoid arthritis. When valdecoxib was approved in November 2001 its list of FDA approved uses did not include acute pain because the drug was found not to be effective for the management of acute pain.

FDA approval of specific uses, such as acute pain, are important for the economic success of new drugs because, legally, a drug company can only promote its products for FDA approved uses as these are the only uses for which drugs have been shown to be safe and effective. However, Pfizer and Pharmacia's failure to gain approval for acute pain did not stop them from promoting valdecoxib for the management of acute pain. This was done by a total perversion of scientific ethics that leaves in question whether or not the peer reviewed medical literature can any longer be relied upon as an objective source of medical science.

We routinely study the FDA's publicly available reviews of data submitted by manufacturers for the approval of new drugs. When the FDA documents for valdecoxib were examined, all of the agency's analyses regarding acute pain had been removed. The FDA's explanation for the removal of this information was that it is considered to be confidential commercial information and not disclosable to the public under the Freedom of Information Act (FOIA). We complained to the FDA that the information about acute pain cannot be considered confidential information as the manufacturer had announced in a press release in March 2001 that they were seeking approval for valdecoxib for the management of acute pain. The agency was sympathetic but the company objected.

While we were unsuccessfully urging FDA to release their safety and effectiveness reviews of valdecoxib for the treatment of acute pain the drug's manufacturer was making an end run around the FDA's approval process. A press release was issued announcing the publication of studies in the May 2002 issue of the Journal of the American Dental Association (JADA) concluding effectiveness for valdecoxib in the treatment of acute pain associated with dental surgery. This publication was co-sponsored by Pfizer and Pharmacia. Three of the five authors were employees of Pharmacia, the corporation’s director of Biostatistics, director of Medical Development, and the clinical vice-president of Medical Development. These three individuals certainly must have known that valdecoxib failed to gain FDA approval for acute pain.

According to a New York Times investigation published November 22, 2002 the JADA study “... helped light a fire under Bextra.” Sales of the drug were reported to have increased 60 percent after the publication of the article. No matter how it is sliced, this Pfizer and Pharmacia sponsored study was a misleading commercial communication (advertisement), and a total perversion of the scientific process.

The following interacting drugs are listed in valdecoxib’s FDA approved professional product labeling or package insert. New scientific techniques have allowed researchers to predict some drug interactions before they have been documented in people. There may be other drugs, especially those in the families of drugs listed below, that also will react with this drug to cause severe adverse effects. The number of new drugs approved for marketing increases the chance of drug interactions, and new drug interactions are being identified with old drugs. Be vigilant. Make sure to tell your doctor and pharmacist the drugs you are taking and tell your doctor if you are taking any of these interacting drugs:

ACCUPRIL, ACEON, ALTACE, benazepril, CAPOTEN, captopril, cholestyramine, COUMADIN, DIFLUCAN, enalapril, fluconazole, fosinopril, furosemide, hydrochlorothiazide, HYDRODIURIL, LASIX, lisinopril, lithium, LITHOBID, LITHONATE, LOTENSIN, MAVIK, moexipril, MONOPRIL, perindopril, PRINIVIL, QUESTRAN, quinapril, ramipril, trandolapril, UNIVASC, VASOTEC, warfarin, and ZESTRIL.

What You Can Do

If you require treatment with an NSAID you should not be taking valdecoxib. There are more effective, safer, and less expensive drugs on the market such as ibuprofen.