AstraZeneca Plc’s Nexium, Pfizer Inc.’s Protonix and Takeda Pharmaceutical Co.’s Prevacid, ulcer drugs also prescribed for indigestion, were linked to a higher risk of bone fractures in older women and to a diarrhea-causing infection, two studies found.
The drugs belong to a family of treatments known as proton pump inhibitors, approved to treat ulcers, acid reflux disease and erosive esophagitis, in which stomach acid causes pain or damage to the esophagus. The medicines have U.S. sales of $13.9 billion annually, according to an editorial accompanying the studies published today in the Archives of Internal Medicine.
The medicines are often prescribed for heartburn and indigestion, which are unapproved uses in people who don’t have ulcers or acid reflux, Mitchell Katz, director of the San Francisco Department of Public Health, wrote in the editorial. Previous studies have estimated between 53 percent and 69 percent of these drugs are taken for inappropriate reasons, the editorial said.
“The problem here is this is a medicine that has serious side effects and 60 to 70 percent of people who are taking it don’t need to be taking it,” Katz said in a telephone interview on May 7. “What will happen once the average person knows about the side effects of these medicines is they’ll say they don’t want to take this.”
Fracture, Infection Risk
Older women who took the medicines had 25 percent more risk of fractures than those who didn’t, according to one study published in the journal. A second report found that people taking the drugs daily had 74 percent more infections with Clostridium difficile, a bacterium that can cause severe diarrhea.
The research data may make consumers aware the treatments are linked to adverse effects and should be taken only by those who need them, Katz said in the editorial.
Worldwide sales of Nexium last year were $4.96 billion, according to a statement from London-based AstraZeneca. The studies were released today after the close of trading.
Heartburn is a burning in the chest, while indigestion may describe a range of symptoms from uncomfortable fullness after a meal to burning or pain in the upper abdomen. Heartburn and indigestion can indicate an ulcer, or may occur without it.
“Patients who have concerns with any of their medications should talk with their health care professional,” Blair Hains, an AstraZeneca spokesman, said in an e-mail on May 7. “Health care professionals will know how to access the most current product label information.”
Takeda, based in Tokyo, is aware of reports linking proton pump inhibitors with fracture and infection risks, said Gilles Delecoeuillerie, executive medical director at Takeda Pharmaceuticals North America. Besides Prevacid, Takeda also sells the proton pump inhibitor Dexilant.
“Takeda has not identified a safety signal for bone fractures or Clostridium difficile infections related to Dexilant or Prevacid,” Delecoeuillerie said in an e-mail on May 7. “It is also important to note that the hypothetical link between PPIs and these events has not been established through a prospective, controlled study.”
Anne Wilson, a spokeswoman for New York-based Pfizer, didn’t immediately respond to an e-mail requesting comment.
In the study of bone fractures led by Shelly Gray, a pharmacy professor at the University of Washington in Seattle, researchers looked at 161,806 postmenopausal women who didn’t have any history of hip fracture and were enrolled in the Women’s Health Initiative, a 15-year research program.
Forearm, Wrist, Spine
Over eight years of the study, there were 21,247 bone fractures. The researchers found that women who used proton pump inhibitors were more likely than those who didn’t to have fractures of the forearm, wrist and spine. Use of the medicines wasn’t associated with hip fractures, they said.
Hains, the AstraZeneca spokesman, said research data on a connection between bone fractures and proton pump inhibitors have been mixed and more studies are needed to understand the causes of the fractures.
Another study, led by Michael Howell of Harvard Medical School in Boston, found that people given therapy to suppress the acid in their stomachs were more likely to develop infections with Clostridium difficile. The cost of treating C. difficile infections has increased in the U.S. to more than $1 billion a year, according to a study cited by Howell.
The researchers had looked at the records of 101,796 people discharged from Beth Israel Deaconess Medical Center during a five-year period. Overall, 665 cases of C. difficile occurred. Those taking proton pump inhibitors daily had 74 percent more infections compared with those not using the treatments.
A third study in today’s journal found that those being treated for C. difficile had a 42 percent increased risk of their infection returning if they were given a proton pump inhibitor within 14 days of their original diagnosis. The study, led by Amy Linsky at Boston Medical Center, examined about 1,200 people in the New England Veterans Healthcare System.
According to Nexium’s prescribing information, decreased stomach acidity that occurs with proton pump inhibitors may allow bacteria to grow and may slightly increase the risk of infections from Salmonella and possibly C. difficile in hospitalized patients.
A fourth research report, from Taiwan, showed that high- dose proton pump inhibitors don’t appear to reduce the rates of additional bleeding, surgery or death in patients with bleeding ulcers more than regular doses.