TUESDAY, Nov. 1, 2005 (HealthDay News) -- Combining common over-the-counter pain relievers such as ibuprofen (Advil, Motrin) or naproxen (Aleve) with aspirin can spell trouble for the stomach, a new study suggests.
Researchers have found that patients who took these medications in combination were at a two to three times higher risk of developing stomach ulcers, perforations and bleeding compared to individuals who took the non-steroidal anti-inflammatory drugs (NSAIDS) without aspirin.
Even taking naproxen or ibuprofen without aspirin increased the risk of these problems, the researchers added.
"There's a synergistic effect with aspirin, if you want to consider it to be synergistic," said study author Joe Biskupiak, a research associate professor of pharmacotherapy at the University of Utah College of Pharmacy in Salt Lake City. "Just because it's over-the-counter doesn't mean it's devoid of risk."
The findings are scheduled to be presented Wednesday at the American College of Gastroenterology annual meetin, in Honolulu.
"This is all confirmatory. This study continues to support both the frequency and danger of multiple NSAID use," added Dr. Mark Fendrick, a professor of internal medicine at the University of Michigan School of Medicine, in Ann Arbor. "This likely remains the most substantial modifiable risk factor to reduce gastrointestinal complications from NSAIDs."
A second study, published Tuesday in the November issue of Clinical Gastroenterology and Hepatology, found chronic use of ibuprofen to be associated with a close to fourfold loss of blood as measured in stool, compared to individuals taking a placebo.
That study, led by Dr. Barry Bowen of McMaster University in Hamilton, Ontario, compared daily amounts of GI bleeding (as evidenced by blood in stool samples) among 68 healthy adult male volunteers tracked over four weeks. Half of the men took a harmless placebo while the other half took a standard dose of 800 milligrams of ibuprofen three times daily.
Men taking ibuprofen experienced daily blood loss 3.64 times that of men taking placebo, the Canadian team noted, with the amount of blood lost varying greatly between volunteers. Based on the findings, "the potential for a serious GI complication should still be considered when ibuprofen is recommended for self-medication," the authors concluded.
There has been mounting evidence to show that NSAIDs are associated with an increased risk of serious gastrointestinal (GI) events, and that adding aspirin exacerbates that risk.
"Depending on who you talk to, this is known but not well-documented," Biskupiak said. "We know that the prescription NSAIDs increase risk. Over-the-counter NSAIDs are a little harder to pin down because it's harder to get data on patients using them. Everybody suspected it, but there hasn't been a lot out there."
This family of drugs also includes Cox -2 inhibitors such as the now-banned Vioxx and Bextra, as well as still-available Celebrex. Cox-2 inhibitors are easier on the stomach and were developed to sidestep the GI problems associated with traditional, "non-specific" NSAIDs.
Now that cox-2s have been shown to be associated with cardiovascular problems, more people are turning back to traditional NSAIDs and are therefore at risk for GI bleeding and other complications.
This study was funded by Pfizer Inc., the maker of Celebrex, the sole cox-2 inhibitor still approved for sale to U.S. consumers. Study co-author Kimberly Howard is a research scientist at Pfizer and helped design the study.
The study is one of the first to look at long-term, real-world usage of OTC non-selective NSAIDs, Biskupiak said. In their study, his team scanned a database containing electronic medical records for more than 3.2 million individuals. In the database, 11,957 patients were listed as taking naproxen (220 mg) and 38,507 patients were on ibuprofen (200 mg).
Among the naproxen users, 2,328 were also taking aspirin while 4,843 of the ibuprofen patients were also taking aspirin.
Those taking ibuprofen were 2.5 times more likely to experience problems such as ulcers, bleeding and perforations than those not taking over-the-counter painkillers. Those taking naproxen were 2.74 times more likely to experience stomach trouble.
Individuals taking both ibuprofen and aspirin were at a 3.36 times higher risk, while those taking naproxen and aspirin faced a 2.07 times higher risk compared with people ibuprofen or naproxen without aspirin.
In a statement, Bayer HealthCare AG, which markets a well-known brand of aspirin as well as naproxen (Aleve), said the results of the Pfizer-funded study are at odds with much of the previous research on the subject, which found no significant increase in GI ulcer complications linked to long-term NSAID use, either alone or in combination with aspirin.
Bayer also pointed out that the University of Utah study is a retrospective trial looking over past data, rather than the research "gold standard," a prospective, randomized, controlled study.
But Biskupiak said the fact the study was funded by the makers of a competing painkiller, Celebrex, shouldn't detract from the significance of the findings.
"As far as impact on Celebrex sales, my guess is that it would be minimal," he said. "While it is realized that Cox-2 agents (like Celebrex) have a better GI side-effect profile (i.e., less likely to cause GI bleeds), the recent problems regarding cardiovascular side effects has probably dampened sales. This study just documents that OTC non-selective NSAIDs are a problem as well, and should be avoided in patients with any risk of GI bleeds."
The study also pointed out the need for more public and physician education, Biskupiak said. One recent study found that just one-third of people at high risk for GI bleeding who were taking NSAID painkillers were also being prescribed medicines to prevent that bleeding.
"A previous phone survey found that patients that are using these drugs don't know about the risk," he said. "They take more than the instructions tell them to take, and don't talk to any medical professionals about it. On the flip side, we in the medical profession probably do a poor job of taking a medication history when it pertains to over-the-counter medications."
"I think there's a need for a little education on both sides of the fence here, for the patients and for the physicians or pharmacists to educate people about the risks and just to publicize it so that people are aware," Biskupiak continued.
More information
For more on NSAIDs, aspirin and related GI problems, head to the American College of Gastroenterology.
