WASHINGTON, D.C. – Many widely prescribed stomach acid-reducing drugs can cause long-term dependence and should carry the strongest possible warning label for this and several other dangerous adverse effects, Public Citizen told the U.S. Food and Drug Administration (FDA) in a petition sent today.

The drugs are proton pump inhibitors (PPIs), so-named because of the mechanism they use to shut off the production of stomach acid. PPIs are one of the most widely used classes of drugs in the United States, with 119 million prescriptions dispensed in 2009 and $13.6 billion in U.S. sales. An estimated 1 of every 20 people in the developed world is taking the medications, which include Nexium, Dexilant, Prilosec, Prilosec OTC, Zegerid, Zegerid OTC, Prevacid, Prevacid 24-Hr, Protonix, Aciphex, Vimovo and numerous generic counterparts, most prominently omeprazole and pantoprazole.

“These drugs are being prescribed far too commonly to people who shouldn’t be taking them,” said Dr. Sidney Wolfe, director of Public Citizen’s Health Research Group. “As a result, 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. 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.”

PPIs are approved to treat gastroesophageal reflux disease (GERD) – sometimes referred to as acid reflux – as well as gastric ulcers, erosive esophagitis and stomach bleeding associated with using non-steroidal anti-inflammatory drugs (NSAIDs). But evidence shows that after using PPIs for a month or more, patients who stop taking the drug make even more stomach acid than before they started the drug, a phenomenon known as rebound acid hypersecretion, which causes acid reflux symptoms to return even worse than before therapy. The symptoms prompt patients to begin taking the PPI again, creating a long-term dependence on these drugs, particularly worrisome for the large number of patients who did not even need the drugs in the first place. As Dr. K.E. McColl, a leading Scottish researcher on adverse effects of PPI use, recently concluded, “The current finding that these drugs induce symptoms [after withdrawal] means that such liberal [mis-] prescribing is likely to be creating the disease the drugs are designed to treat and causing patients with no previous need for such therapy to require intermittent or long-term treatment.”

In addition to creating dependency, PPIs increase the risk for several serious conditions, including fractures of the hip, spine and wrist; an increased risk of serious infections such as pneumonia and C. difficile diarrhea; and severe magnesium deficiency, which can cause life-threatening cardiac arrhythmias. PPIs also may reduce the effectiveness of other drugs used to treat heart attacks and cancer, and in some cases, can cause vitamin B12 deficiency and kidney failure. Although some of these side effects already are mentioned somewhere in the labels (not the case for the dependence), none – including those that are life-threatening – are displayed prominently as black box warnings, the strongest possible warning.

Therefore, physicians may not be aware of the serious risks associated with PPI therapy, resulting in a large number of unnecessary prescriptions. Studies have shown that up to two-thirds of all people taking PPIs do not even have a condition that the drugs are designed to treat, and the drugs are often taken for much longer periods of time than they are approved for. In addition, PPIs are commonly prescribed for conditions such as acid reflux that could be treated with safer alternatives that are often just as effective.

Public Citizen is petitioning the FDA to require that more prominent black box warnings and other safety information be added to the product labels of all PPIs on the market. Public Citizen also is calling for patient medication guides to be distributed with all PPIs and for the makers of the drugs to send a letter to doctors alerting them to these adverse effects and of the need to try safer alternatives first for conditions such as GERD.

Dr. Helge L. Waldum, a co-petitioner with Public Citizen, is head of the Department of Digestive and Liver Diseases at Trondheim University Hospital in Norway and author of 135 medical journal articles related to the topics of this petition, among them the first trial to show that patients could become dependent on PPIs through the rebound effect. In a statement released today, he noted: “Given that most people on PPIs long-term may not even have a documented need for the medication, and that for those that are on these drugs for legitimate reasons, several safer alternatives exist, the risks greatly outweigh any benefit in most patients on PPIs. I therefore urge the FDA to act promptly on the recommendations outlined in this petition.”

Robert Kuttner, a well-known journalist and co-editor of the American Prospect, long suffered from severe acid reflux and became dependent on PPIs after a particularly severe episode. After years of unsuccessfully trying to control his symptoms with ever higher doses of the PPI, the reflux resolved only after a physician tapered him off the drug to another therapy. Now largely symptom-free, Kuttner, who released a statement today in support of Public Citizen’s petition, concluded: “My experience certainly seems to confirm the pattern of PPI medication causing – or in my case, seriously aggravating – the condition that it supposedly treats. In my case, the PPI seemed to have primed my system to produce increasing amounts of acid so that over time I was more prone to more attacks triggered by ever more minor departures from a very low fat diet … The ever-increasing amounts of PPI helped only temporarily and required dependence on even higher doses, and so on, over several cycles. Only getting off the PPI reversed what seemed to be a chronic and progressive condition.”

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