Comparative Gastrointestinal (GI) Toxicity of Six Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

The British equivalent of our Food and Drug Administration (FDA), in the April 2002 issue of its newsletter Current Problems in Pharmacovigilance, published a ranking of the relative gastrointestinal (GI) toxicity of some of the widely used older nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are commonly used for acute pain and the treatment of the symptoms of osteo- and rheumatoid arthritis.

Adverse drug reaction reports, epidemiological studies and the published medical literature all were used to rank the NSAIDs’ relative toxicity. Ibuprofen (MOTRIN, ADVIL) came out on top and was the only NSAID ranked as having the lowest risk of GI toxicity. Naproxen (NAPROSYN, ALEVE), diclofenac (VOLTAREN), ketoprofen (ORUDIS, ORUDIS KT), indomethacin (INDOCIN), and piroxicam (FELDENE) were grouped together as having intermediate risk. One NSAID, not marketed in the U.S., was listed as having a high risk of toxicity. The British authorities noted that piroxicam may be associated with a higher risk than the other NSAIDs in the intermediate group.

The British findings confirm and extend evidence that we presented in December 1994 to the FDA in support of a petition calling for the withdrawal of piroxicam from the market because of its negative effects on the GI tract in comparison to the other NSAIDs (see the March 1995 issue of Worst Pills, Best Pills News). Our petition was based on published studies that had reported the risk of severe GI toxicity (bleeding, ulceration, or perforation) associated with the individual NSAIDs. We found that the risk of GI complications was consistently lower with ibuprofen and that the increased risk of GI toxicity with piroxicam compared to ibuprofen was 6.8 times greater.

The evidence continues to support ibuprofen as the least GI toxic NSAID. This includes the so called COX-2 NSAIDs celecoxib (CELEBREX) and rofecoxib (VIOXX). Celecoxib was found to be no safer than ibuprofen in a head-to-head comparison and rofecoxib has not been tested directly against ibuprofen.

Though the evidence continues to support the relative safety of ibuprofen compared to other NSAIDs it is not without toxicity. All NSAIDs can cause bleeding, ulceration, or perforation of the GI tract that can lead to hospitalization and death.

What You Can Do

If the following symptoms develop while you are taking an NSAID, stop the drug immediately and contact your doctor: severe abdominal or stomach pain, cramping or burning, severe and continuing nausea, heartburn or indigestion, bloody or black, tarry stools, vomiting blood or material that looks like coffee grounds, or spitting up blood.

The risk of gastrointestinal toxicity from these drugs increases with increasing doses and the length of treatment.