MedPage Today ~ October 26, 2009 ~ FULL TEXT
Even at low doses, naproxen (Aleve, Anaprox, Naprosyn, Naprelan) may increase the risk
of upper gastrointestinal complications, researchers said here.
Patients taking a 500-mg/day dose had a 2.5-fold increased risk of hospitalization from complicated gastric or duodenal ulcer, while those on the 750-mg/day dose had almost a threefold increased risk, Gurkirpal Singh, MD, of Stanford University, and colleagues reported at the American College of Gastroenterology meeting. 
The 1,000-mg/day dose carried more than a threefold increased risk of hospitalization. “We found that naproxen use is not safe even at lower doses,” Singh said. “We need to be careful about prescribing it, even in lower doses.” The lowest doses are available over the counter.
In large studies comparing other nonsteroidal anti inflammatory drugs (NSAIDs) and COX-2 inhibitors, naproxen has been associated with fewer serious cardiovascular risks. That led to several recommendations for naproxen to be the drug of choice for patients with heart problems, the researchers said.
But at high, prescription-level doses, naproxen has been linked with serious upper gastrointestinal toxicity, and it was unclear whether lower doses — under 1,000 mg/day — might also increase the risk, the researchers said.
“We wanted to see if that’s also true at lower doses because lots of patients take naproxen at lower doses,” Singh said.
So the researchers conducted a case-control study of 688,424 California Medicaid patients who were treated with an NSAID or COX-2 inhibitor between January 1999 and June 2005.
They used data from the MediCal database, which tracks the largest Medicaid program in the U.S.
The main outcome was hospitalization for gastric or duodenal ulcer that included complications such as hemorrhage, perforation, or obstruction.
A total of 11,303 patients were hospitalized, and the researchers matched them to 45,212 controls.
They found an increased risk of hospitalization with all doses of naproxen, in a dose-dependent fashion, as follows:
- 1,000 mg/day, 3.13-fold increased risk (95% CI 2.71 to 3.61)
- 750 mg/day, 2.95-fold increased risk (95% CI 2.34 to 3.73)
- 500 mg/day, 2.51-fold increased risk (95% CI 1.61 to 3.92)
The researchers said that the risks were also significantly higher compared with remote NSAID use or COX-2 selective inhibitor use (P<0.001).
Singh noted that clinicians should "strongly consider" concomitant gastrointestinal protective therapy for at-risk patients, regardless of naproxen dose, to protect against gastric and duodenal ulcers.
"Clinicians should use the lowest dose [of naproxen] for the shortest period of time," Singh said. "And if you're dealing with a high-risk patient, add a proton pump inhibitor."
Singh said previous research has shown that adding a proton pump inhibitor to high-dose naproxen use cuts the risk of complications in half. For further study, he suggested evaluating whether that is also the case for low-dose patients.
Singh G, et al
Naproxen use increases the risk for complicated gastroduodenal ulcers in a dose-dependent fashion
American College of Gastroenterology (ACG) 2009; Abstract P55.