Gastroenterology > GERD
Consumer Group Urges Boxed Warning for PPIs
by John Gever John Gever, Senior Editor, MedPage Today August 23, 2011
Citing research showing that withdrawal of proton pump inhibitors (PPIs) leads to severe rebound acid secretion -- potentially leaving patients permanently dependent on the drugs -- the consumer group Public Citizen has told the FDA that it should require black-box warnings with the drugs.
"Millions of people are needlessly setting themselves up to become dependent on PPIs while exposing themselves to the serious risks associated with long-term therapy," said Sidney Wolfe, MD, head of the group's health research group, in a statement.
"The FDA should act immediately to ensure that patients and physicians are adequately warned of these effects and reminded of the many safer alternatives for common conditions such as acid reflux."
Public Citizen filed a petition with the FDA formally requesting warnings on this and other side effects of PPIs, in the form of updated labels, patient medication guides, and "Dear Doctor" letters.
The group charged that many patients are taking PPIs without a clear need for them. Public Citizen estimated that about 5% of the population in developed nations is taking these medications.
The medications, which include such products as omeprazole (Prilosec), pantoprazole (Protonix), and lansoprazole (Prevacid), are approved for gastroesophageal reflux disease (GERD), gastric ulcers, erosive esophagitis, and gastric bleeding associated with nonsteroidal anti-inflammatories.
The rebound phenomenon and the potential for dependence was reported in 2009 by Danish researchers, who found that half of healthy volunteers suffered heartburn or related symptoms after a two-month course of esomeprazole (Nexium).
As the authors of that study noted, "patients with ambiguous symptoms that are not truly acid related may be prescribed a PPI empirically, but may find it difficult to withdraw from therapy because of the development of true acid-related symptoms."
However, not all research has supported the rebound phenomenon.
For example, a study published last week in the American Journal of Gastroenterology by David Metz, MD, of the University of Pennsylvania in Philadelphia, and colleagues found no signs of worsened symptoms following four to eight weeks of PPI treatment.
Metz and colleagues had analyzed data from trials of lansoprazole or dexlansoprazole involving 287 patients with erosive esophagitis, who were randomized to placebo following the PPI course.
Other risks associated with PPIs cited by Public Citizen as deserving boxed warnings include:
Hip, spine, and wrist fractures
Pneumonia and C. difficile infections
Interactions with other medications
These effects are already described in the current product labels, but Public Citizen said they should receive "the strongest possible warning."
It also noted that the potential for dependence is not currently listed on PPI labels at all.
In addition to the boxed warnings, Public Citizen recommended that the FDA order manufacturers to issue patient medication guides and send letters to doctors highlighting the risks. It said the letters should also tell physicians that safer treatments should be offered first to patients with GERD.
However, the group stopped short of requesting that over-the-counter versions of PPIs be withdrawn.
Physicians contacted by MedPage Today and ABC News agreed that the rebound phenomenon is real and significant, but they were divided as to whether it's serious enough to warrant a boxed warning.
Kenneth DeVault, MD, a gastroenterologist at the Mayo Clinic in Jacksonville, Fla., said he didn't think more warnings were needed.
"Honestly, the risks of these medications, even when over the counter, are much less than some other common drugs such as nonsteroidal anti-inflammatories and even aspirin," he said in an email.
A similar reaction was voiced by Curtis Stine, MD, of the family medicine department at Florida State University in Tallahassee.
Asked if the FDA should require stronger warnings, he responded, "I don't think so; however, I do agree that this class of medicines is overprescribed, and I suggest that some kind of better professional education of providers/physicians is needed."
But Lee Green, a family medicine specialist at the University of Michigan, told MedPage Today and ABC News that a boxed warning was a good idea. "Unfortunately, that's what it takes to get doctors to prescribe thoughtfully. The PPIs are badly overused," he said in an email.
Green also said that the key to stopping PPIs is to let patients know that symptoms may recur for a while, "so they don't think they need to go back on the drug."
This article was developed in collaboration with ABC News.
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