Infections, Fractures Linked to Acid Reflux Drugs

Popular PPI Antacids Linked to C. diff Infection, Broken Bones, Other Risks

By Daniel J. DeNoon
WebMD Health News

Reviewed By Laura J. Martin, MD

May 10, 2010 -- The popular class of antacids that includes Aciphex, Dexilant, Nexium, Prevacid, Prilosec, and Protonix increases the risk of C. diff infection and bone fracture, new studies find.

The drugs all are proton pump inhibitors (PPIs), the most powerful class of antacid drugs. It's the third highest-selling class of drugs in the U.S. Each year, doctors write 113.4 million prescriptions for the drugs. Two, Prevacid and Prilosec, are available without prescription.

The drugs do a great job of reducing stomach acid. They're not only far more powerful than simple antacids (such as Maalox, Rolaids, and Tums) but also reduce stomach acid more than the H2RA drugs Axid, Pepcid, Tagamet, and Zantac.

PPIs are supposed to be used only for serious conditions, but often they are taken for simple heartburn. Moreover, doctors tend to overprescribe PPIs for hospitalized patients. What's the harm?

More than many patients should risk, according to a series of articles in the May 10 issue of Archives of Internal Medicine.

PPIs Raise C. diff Risk

Perhaps the scariest PPI risk is serious infection with C. difficile bacteria, a hard-to-cure infection that causes severe diarrhea. Stomach acid does a great job of keeping C. diff down. PPIs, however, keep stomach acid below the levels that protect against this bad bug.

Now Boston Medical Center researcher Amy Linsky, MD, and colleagues find that hospital patients treated for C. diff infections are 42% more likely to have their C. diff infection come back if they take PPIs (a 25.2% risk vs. an 18.5% risk).

In another study, Beth Israel Deaconess Medical Center researcher Michael D. Howell, MD, MPH, and colleagues find that the risk of getting C. diff while in the hospital is higher for patients receiving PPIs than for those getting H2RAs or no antacids.

The risk for an individual patient is not great. There's about one extra C. diff infection for every 533 patients treated with the drugs. But about 60% of U.S. hospital patients get antacids. That translates into tens of thousands of extra C. diff cases each year.

PPIs Increase Fractures

A Canadian study in 2008 linked long-term PPI use to bone fractures in middle-aged adults. It was far from conclusive, as people had to use the drugs for seven years before fracture risk increased.

Now Shelly L. Gray, PharmD, of the University of Washington, Seattle, and colleagues report on data from more than 130,000 women enrolled in the Women's Health Initiative.

The good news is that the study found no significant link between PPI use and hip fracture. Moreover, PPI use was not linked to significantly lower bone mineral density.

However, women who reported current PPI use were 47% more likely to have had a spine fracture, 26% more likely to have a forearm or wrist fracture, and 25% more likely to have any kind of fracture.

The risk, Gray and colleagues conclude, is "modest."

The benefits of PPIs may not justify their risks for many people, suggests Mitchell H. Katz, MD, of the San Francisco Department of Public Health.

"PPIs have been over-prescribed," Katz notes in an editorial accompanying the studies. "Between 53% and 69% of PPI prescriptions are for inappropriate indications."

Katz suggests that for most patients, the PPI risks outweigh their benefits. He recommends that doctors offer other treatments for heartburn, including non-drug treatments such as stress reduction, weight loss, and smoking cessation.

When PPIs are used, Katz advises doctors to use shorter courses and lower doses when possible.

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SOURCES: Katz, M.H. Archives of Internal Medicine, May 10, 2010; vol 170: pp 747-748.

Howell, M.D. Archives of Internal Medicine, May 10, 2010; vol 170: pp 784-790.

Linsky, A. Archives of Internal Medicine, May 10, 2010; vol 170: pp 772-778.

Gray, S.L. Archives of Internal Medicine, May 10, 2010; vol 170: pp 765-771.

Grady, D. and Redberg, R.F. Archives of Internal Medicine, May 10, 2010; vol 170: pp 749-750.

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