PPI inhibitors listed, short FDA filing article
Detailed FDA filing on PPI--wp

BACKGROUND INFO ON PPI halfway down the page wikipedia 


I can only wonder why an addicting antacid, of the class of Protein Pump Inhibitors (PPI), is given with an antibiotic for the eradication of the cause of over 85% of all ulcers.  It simply is another coupe that PhARMA has pulled to build the sales of a patented drug.  It is not medicine in the public interest.  Read below how the use of the PPI family of drugs are addicting.  The stomach makes a dilute (about 5%) solution of hydrochloric acid (HCl) to promote digestion.  The PPI reduce the product of HCl.  The H stands for hydrogen, and when it is bound to Chlorine (Cl) and is hydrolyzed (dissolved) in water, the Cl receives the sole electron of the H, and there converting the H to a proton.  A drug which interferes with this process, PhARMA, gave the name of proton pump inhibitor.  By why take a patented drug when Maalox and other over the counter preparations work better?


Aug. 23, 2011    http://www.citizen.org/pressroom/pressroomredirect.cfm?ID=3403


Many Popular Stomach Acid-Reducing Drugs Are Habit-Forming, Dangerous

Nexium, Prilosec and Other Proton Pump Inhibitors Are Overprescribed, Should Carry Strongest Possible Warning, Public Citizen Tells FDA in Petition


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.”


Wikipedia     http://en.wikipedia.org/wiki/Omeprazole

Omeprazole (INN) (  /ˈmɛprəzl/) (Prilosec and generics) is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD/GERD), laryngopharyngeal reflux (LPR) and Zollinger–Ellison syndrome. Omeprazole is one of the most widely prescribed drugs internationally and is available over the counter in some countries.

Medical uses

See also: Proton pump inhibitor

Use in medicine to treat GERD (Gastro esophagel reflux disease), gastric and duodenum ulceration and gastritis.

Use in Helicobacter pylori eradication

Omeprazole is combined with the antibiotics clarithromycin and amoxicillin (ormetronidazole in penicillin-hypersensitive patients) in the 7–14 day eradication triple therapy for Helicobacter pylori. Infection by H. pylori is the causative factor in the majority of peptic and duodenal ulcers.[3]

Mechanism of Action

Omeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. By acting specifically on the proton pump, omeprazole blocks the final step in acid production, thus reducing gastric acidity.[4]




 August 23, 2011

Margaret A. Hamburg, M.D.

Commissioner U.S. Food and Drug Administration

Department of Health and Human Services WO 2200

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

Dear Dr. Hamburg,


As a physician and life-long researcher on the adverse effects of proton pump inhibitors (PPIs), I strongly support the attached petition for Black Box Warnings and other labeling changes to the labels of all PPIs currently on the market and have joined Public Citizen as a co-petitioner.

My research began in 1974 on the regulation of gastric acid secretion, and particularly the central role of gastrin in this process. Through in vitro studies in isolated organs, in addition to in vivo animal and, most importantly human studies, our group was the first to show that gastrin, a critical hormone in regulating digestion, functionally stimulates acid secretion primarily through effects on histamine release. A key finding was that, once the PPIs were discontinued, ECL cell hyperplasia persisted for weeks and even a few months causing levels of acid secretion higher than those seen before starting PPI therapy.

From these initial animal data on the effect of PPIs on gastrin with secondary ECL cell hyperplasia, it was difficult to accept that these drugs should not induce a rebound acid hypersecretion (RAHS) in humans, and in a 1996 study on patients with reflux esophagitis, we were the first to show such an effect. We reasoned that this RAHS effect was the cause of the “dependence” on PPIs that many clinicians in the field have described. As outlined in the petition, our findings have been confirmed by a wave of subsequent studies showing, in randomized-controlled trials, that patients with gastroesophageal reflux disease (GERD) can become “dependent” on PPIs through the RAHS effect after as little as 2 weeks of therapy. In 2009 in another randomized trial, even previously healthy subjects – with no history of GERD – showed the RAHS effect after two weeks of PPI therapy, thus confirming that the effect is not merely a recurrence of symptoms after stopping therapy.

This area of research has become increasingly important since the proliferation of PPI use over the past 10-15 years to become one of the most widely used classes of medications in the world. However, throughout my career I have been struck by the difficulties in getting manuscripts published describing this and other adverse effects of PPIs. Furthermore, it has been disappointing to experience that clinicians and scientists dismiss

the alteration by PPIs of central biological functions and believe that some of these basic functions can be removed without adverse consequences.

For instance, one of the most important functions of the acidic gastric juice is to kill swallowed micro-organisms. Thus, by suppressing gastric acid secretion and removing this critical protective mechanism against infection, PPIs have been shown to increase the risk of several infections, such as pneumonia and C. difficile diarrhea. This represents just one of many life-threatening side effects that have been associated with long-term PPI use. In addition, several animal studies have shown a possible link between PPI use and gastric cancer, particularly in patients with a common stomach infection, H. pylori, the same bacteria implicated in peptic ulcer disease.

Given that most people on PPIs long-term do 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 Public Citizen’s petition to require urgent labeling changes to all PPIs, including Black Box Warnings describing these serious adverse effects.


Helge L. Waldum, M.D., PhD,

Professor of Medicine and Head of Department of Digestive and Liver Diseases Norwegian National University of Science and Technology

Trondheim University Hospital


Trondheim, Norway