FDA Directive: Prescription NSAID Product Labeling

•A boxed warning regarding the potential serious adverse CV events and the serious, and potentially life-threatening GI adverse events associated with the use of this class of drugs.

•A contraindication for use in patients who have recently undergone coronary artery bypass surgery.

•A Medication Guide for patients regarding the potential for CV and GI adverse events associated with the use of this class of drugs. The Medication Guide will be required to be given to patients at the time each prescription is dispensed. The Medication Guide will also inform patients of the need to discuss with their doctor the risks and benefits of using NSAIDs and the importance of using the lowest effective dose for the shortest duration possible if treatment with an NSAID is warranted for an individual patient.

Patients who are taking a prescription non-selective NSAID should discuss questions or concerns about this new information with their physician.

OTC Non-Selective NSAIDs
The available data do not suggest an increased risk of serious CV events for the short-term, low-dose use of the NSAIDs available over the counter. FDA will allow these products to remain on the market, but will request changes to the label to better inform consumers regarding the safe use of these products.

FDA will ask manufacturers of all OTC products containing ibuprofen (Motrin, Advil, Ibu-Tab 200, Medipren, Cap-Profen, Tab-Profen, Profen, Ibuprohm), naproxen (Aleve), and ketoprofen (Orudis, Actron) to revise their labeling to include:

•More specific information about the potential CV and GI risks,

•Instructions about which patients should seek the advice of a physician before using these drugs,

•Stronger reminders about limiting the dose and duration of treatment in accordance with package instructions, unless otherwise advised by a physician, and

•A warning about potential skin reactions.

Patients who are taking an OTC NSAID should carefully follow the labeled directions, particularly with regard to dose and duration of use, and should contact their physician regarding any questions or concerns they may have about this new information.

Note: Aspirin is a nonselective NSAID. However, aspirin is also a platelet inhibitor and has been shown in clinical trials to reduce the risk of CV events. Patients taking aspirin to prevent CV events should NOT stop taking it, unless specifically advised to do so by their physician.

FDA expects that these actions will further encourage the safe and effective use of these products. FDA will continue to notify health care providers and patients in a timely fashion as new information becomes available.

FDA urges health care providers and patients to report adverse event information the MedWatch program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), or by the Internet at http://www.fda.gov/medwatch/index.html.

COX-2 Selective Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Prescription and Over-the-Counter (OTC) Non-selective NSAIDs Approved Under New Drug Application (NDA) Abbreviated New Drug Application (ANDA)

COX-2 Selective NSAID

Non-Selective NSAIDs

Chemical Name/Brand Name:

Diclofenac: Cataflam, Voltaren, Arthrotec (combination with misoprostol)

Diflunisal: Dolobid

Etodolac: Lodine, Lodine XL

Fenoprofen: Nalfon, Nalfon 200

Flurbiprofen: Ansaid

Ibuprofen: 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 (combination with hydrocodone), Combunox ( combination with oxycodone).

Indomethacin: Indocin, Indocin SR, Indo-Lemmon, Indomethagan

Ketoprofen: Oruvail, Orudis, Actron

Ketorolac: Toradol

Mefenamic Acid: Ponstel

Meloxicam: Mobic

Nabumetone: Relafen

Naproxen: Aleve, Naprosyn, Anaprox, Anaprox DS, EC-Naproxyn, Naprelan, Naprapac (copackaged with lansoprazole)

Oxaprozin: Daypro

Piroxicam: Feldene

Sulindac: Clinoril

Tolmetin: Tolectin, Tolectin DS, Toelctin 600

*There are many OTC Combinations with ibuprofen: Advil Cold And Sinus, Advil Cold, Advil Allergy Sinus, Children's Advil Allergy Sinus, Ibuprohm Cold and Sinus, Sine-Aid IB, Children's Motrin Cold.

U.S. Food and Drug Administration (FDA)
Department of Health and Human Services
Center for Drug Evaluation and Research
April 7, 2005