FDA Announces Changes for All NSAIDs; Bextra Withdrawn From Market

The U.S. Food and Drug Administration has announced actions which will be taken regarding the marketing of NSAIDs (nonsteroidal anti-inflammatory drugs). The actions include changes for COX-2 inhibitors, as well as prescription and non-prescription (over-the-counter) NSAIDs.

Highlights of FDA Action

Pfizer has been asked to withdraw Bextra from the market because "the overall risk versus benefit profile for the drug is unfavorable." Pfizer has agreed to suspend sales and marketing of Bextra in the U.S. pending further discussions with the FDA.

The FDA has asked Pfizer to include a boxed warning in the Celebrex label (package insert) stating an increased risk of cardiovascular events and potentially life-threatening gastrointestinal bleeding associated with its use.

The FDA has asked manufacturers of all other prescription NSAIDs to revise their labels to include the boxed warning stating an increased risk of cardiovascular events and potentially life-threatening gastrointestinal bleeding associated with their use.

Manufacturers of Celebrex and all other prescription NSAIDs will be asked to revise labeling to include a Medication Guide for patients to increase awareness of the potential for cardiovascular and gastrointestinal adverse events associated with use of this class of drugs.

The FDA is also asking manufacturers of all over-the-counter NSAIDs (i.e. Aleve, Advil) to revise labels to include more specific information about potential cardiovascular and gastrointestinal risks, and safe use of the drugs.

The FDA is asking manufacturers of over-the-counter NSAIDs to include a warning about potential skin reactions. The label of prescription NSAIDs already includes warnings about potential skin reactions.

These actions by the FDA follow scrutiny of NSAIDs and COX-2 inhibitors provoked by the voluntary withdrawal of Vioxx by Merck in September 2004. After analyzing scientific data, including data collected after the drugs were approved, and a joint meeting of the FDA's Arthritis and Drug Safety and Risk Management Advisory Committees held February 16-18, 2005, the FDA made its decision.

Why Has Bextra Been Singled Out?

The reasons given for the withdrawal of Bextra from the market include:

The lack of adequate data on the cardiovascular safety of long-term use of Bextra, along with the increased risk of adverse cardiovascular events in short-term coronary artery bypass surgery trials that FDA believes may be relevant to chronic use.

Reports of serious and potentially life-threatening skin reactions, including deaths, in patients using Bextra. The risk of these reactions in individual patients is unpredictable, occurring in patients with and without a prior history of sulfa allergy, and after both short- and long-term use.

Lack of any demonstrated advantages for Bextra compared with other NSAIDs.

What Should Patients Do Who Take Bextra Or Other NSAIDs?

Patients currently taking Bextra should contact their doctor to consider alternatives to Bextra. Decisions about which specific drug you should take to treat your arthritis symptoms should be made by consulting your doctor and considering your individual condition and treatment needs.

Please Read: Questions & Answers: FDA Regulatory Actions On COX-2 Inhibitors & NSAIDs

The decision applies to the marketed COX-2 selective drugs (Bextra and Celebrex) as well as the non-selective NSAIDs.

This includes these COX-2 Selective NSAIDs:

• Celecoxib brand name Celebrex
• Valdecoxib brand name Bextra
• Rofecoxib brand name Vioxx

This also includes Non-selective NSAIDs including:

• Diclofenac brand names Cataflam, Voltaren, Arthrotec (combination with misoprostol)
• Diflunisal brand name Dolobid
• Etodolac brand names Lodine, Lodine XL
• Fenoprofen brand names Nalfon, Nalfon 200
• Flurbiprofen brand name Ansaid
• Ibuprofen brand names Motrin, Motrin IB, Motrin Migraine Pain, Advil, Advil Migraine Liqui-gels, Ibu-Tab 200, Medipren, Cap-Profen, Tab-Profen, Profen, Ibuprohm, Children’s Elixsure, Vicoprofen, Combunox, Note: there are over-the-counter ibuprofen products and many OTC combinations.
• Indomethacin brand names Indocin, Indocin SR, Indo-Lemmon, Indomethegan
• Ketoprofen brand names Oruvail, Orudis, Actron, Note: there are over-the-counter ketoprofen products.
• Ketorolac brand name Toradol
• Mefenamic Acid brand name Ponstel
• Meloxicam brand name Mobic
• Nabumetone brand name Relafen
• Naproxen brand names Aleve, Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Naprelan, Naprapac, Note: there are over-the-counter naproxen products.
• Oxaprozin brand name Daypro
• Piroxicam brand name Feldene
• Salsalate brand name Disalcid
• Sulindac brand name Clinoril
• Tolmetin brand names Tolectin, Tolectin DS, Tolectin 600

For More Information From The FDA

You can call 1-888-INFO-FDA.

_{Sources: FDA, http://www.fda.gov; MedWatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm; FDA News, http://www.fda.gov/bbs/topics/news/2005/NEW01171.html}