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Avoiding Overuse of Proton Pump Inhibitors (PPIs)

Worst Pills, Best Pills Newsletter article March, 2008

Doctors frequently overprescribe PPIs, drugs commonly used to stop the secretion of stomach acid, and, as a result, in addition to quarterbacking the waste of billions of dollars, expose patients to the risk of serious side effects – including pneumonia, osteoporosis and kidney disease.

A January article in the British Medical Journal reviewed evidence for the international epidemic of overuse of proton pump inhibitors (PPI), drugs used to treat ulcers and gastroesophageal reflux disease...

Doctors frequently overprescribe PPIs, drugs commonly used to stop the secretion of stomach acid, and, as a result, in addition to quarterbacking the waste of billions of dollars, expose patients to the risk of serious side effects – including pneumonia, osteoporosis and kidney disease.

A January article in the British Medical Journal reviewed evidence for the international epidemic of overuse of proton pump inhibitors (PPI), drugs used to treat ulcers and gastroesophageal reflux disease (GERD).

The drugs are massively used in the U.S. In 2006 alone there were 70 million prescriptions filled in U.S. pharmacies for the four leading PPI drugs: esomeprazole (NEXIUM), lansoprazole (PREVACID), pantoprazole (PROTONIX) and rabeprazole (ACIPHIX), for sales totaling $10.5 billion. This does not even include over-the-counter omeprazole (PRILOSEC).

And, for many people, these drugs are prescribed unnecessarily.

The British Medical Journal article referred to a study of patients in a hospital in Michigan. According to the article, 10 percent of the patients were taking a PPI when they entered the hospital and another 50 percent were prescribed the drugs during their hospital stay, mostly to prevent GERD, commonly called heartburn. By the time they were discharged from the hospital, more than 40 percent of the patients were taking a PPI – more than four times the number taking the drug when admitted. According to the authors, only 10 percent of those on acid suppressive therapy (mainly PPIs) were found to have an acceptable indication for these drugs.

This international review also found a similar trend of overprescribing PPIs in Sweden. In a group of patients who had been taking PPIs for four years, 27 percent were able to discontinue the drug altogether. Similarly, in Wales, a prospective audit of a series of patients admitted as a medical emergency to a hospital found that a quarter of patients were taking a proton pump inhibitor. In only half of the patients was the indication for the drug deemed appropriate. In hospital patients taking PPIs in Australia, Ireland and the UK, 63 percent, 33 percent and 67 percent, respectively, did not meet their country’s criteria for taking the drugs.

The overprescribing of these drugs not only wastes billions of dollars and forces patients to bear these unnecessary expenses – especially in the U.S. – but also puts patients at unnecessary risk of side effects. 

Side effects
The following information comes from a review of published medical journal articles other than the one on overuse excerpted from the British Medical Journal.

Increased risk of hip fractures
In a study involving more than 13,000 patients with hip fractures, the use of PPI therapy is associated with a significant increase – 44 percent – in the risk of hip fractures. The highest risk is seen among those receiving high-dose PPI therapy.

There is a sharp increase in the risk of hip fracture within one year of therapy, as well as a continued risk during the duration of the treatment. Patients’ inability to properly absorb calcium may potentially explain the increased risk, according to the study.

Acute kidney inflammation
All of the PPIs can, in rare circumstances, also cause a particular type of inflammation of the kidneys, known as acute interstitial nephritis or AIN. According to a review on the effects of PPIs on the kidney, there are an ever increasing number of cases of AIN associated with PPI therapy. From a review of patients in many different locations, PPIs appear to be the most common cause of drug-induced AIN. It seems to be agreed that although most patients with PPI-induced AIN recover kidney function, many are left with some level of chronic kidney disease.

Increased risk of community-acquired pneumonia
There is an almost two-fold increase in pneumonia in people while using PPIs and a slightly lower – although still significant – increased risk in people using histamine2 blockers such as cimetidine (TAGAMET). In both instances, the reduction of gastric acid secretion by acid-suppressive therapy allows some bacteria to thrive, which can ultimately increase the risk of pneumonia.

Approved uses for PPIs
Lansoprazole, omeprazole, esomeprazole, pantoprazole and rabeprazole are all close chemical relatives. These drugs are approved for the short-term treatment of GERD, and all but pantoprazole are also approved for duodenal and stomach ulcers resistant to treatment with antacids and histamine2- blockers. All the PPIs except pantoprazole are also approved for use in combination with antibiotics to treat ulcer disease caused by the bacterium Helicobacter pylori. Omeprazole is available over-the-counter, but the others are available by prescription only. The drugs seem to work similarly: Most studies do not show significant differences between the different PPIs for the healing of GERD, duodenal ulcer or Helicobacter pylori eradication.

Lansoprazole, omeprazole, pantoprazole and rabeprazole are also indicated for the treatment for Zollinger-Ellison syndrome, a rare hormonal disorder characterized by excessive stomach acid production due to a stomach tumor. The PPIs do not alter the course of this syndrome and the length of treatment for this condition is indefinite. To maintain effectiveness in treating Zollinger-Ellison syndrome, the dose may need to be increased annually. After long-term treatment, vitamin B12 stores may be depleted in strict vegetarians and the elderly and hence might need to be monitored.

What you can do

Alternatives to PPIs
There are non-drug treatments that do not pose any safety concerns as well as less expensive drugs that may be effective. Patients should try the following non-drug treatments before using any drugs for heartburn.

Instead of using PPIs, patients should avoid alcohol, smoking, tight clothing and foods (e.g., fatty foods, onions, caffeine, peppermint and chocolate) that trigger the condition. In addition, it is best to avoid food, and particularly alcohol, within two or three hours of bedtime. When sleeping, elevate the head of the bed about six inches or sleep with extra pillows.

For both heartburn and ulcers, it is important to avoid drug-induced causes. Aspirin, ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause ulcers. Ask a doctor if acetaminophen could be substituted for these drugs. Check with a doctor about the osteoporosis medications alendronate (FOSAMAX) and risedronate (ACTONEL), which irritate the esophagus.

If these measures are not effective, try simple over-the-counter (OTC) antacids such as a generic aluminum hydroxide and magnesium hydroxide product (MAALOX, MAALOX TC). If symptoms worsen or bleeding occurs, call a doctor.

If this does not relieve symptoms, one of the family of stomach acid-blocking drugs known as histamine2-blockers can be tried. This family includes cimetidine (TAGAMET), famotidine (PEPCID), nizatidine (AXID) and ranitidine (ZANTAC). These drugs partially prevent production of the acid. Histamine2-blockers relieve heartburn pain more quickly than PPIs and are available in both OTC and prescription strengths.

Consult with a physician if the OTC histamine2-blockers do not give adequate relief of symptoms after 14 days.

Ways to reduce the use of these drugs if you are taking them
In a recent review entitled Risks versus Benefits of Long-Term Proton Pump Inhibitor Therapy in the Elderly, the author, a nurse, points out the ever important point that “When prescribing medications, the goal of therapy is to achieve a desired beneficial effect while minimizing any potential adverse effects.” The author goes on to say:

Using the lowest possible dose is one way to help achieve this goal. Frequently, the original prescriber is a specialist such as a gastroenterologist or ear, nose, and throat physician, and subsequent follow-up is assumed to be carried out by a primary care physician. Overuse is a common problem because many providers are reluctant to step down or discontinue a medication initiated by another practitioner. 

Several potential prescribing modalities are available with PPI use. Empirical treatment begins with a short course of continuous dosing dependent on the gastric disorder being treated. Ondemand therapy allows the patient to decide when to take a PPI in response to symptoms. Intermittent therapy allows patients to take a PPI for a short period of time, such as two to four weeks, for symptom control followed by a treatment- free period that can last several months. Step down therapy is another option and entails decreasing the dose, decreasing frequency, or changing to other modalities, such as histamine-2 receptor antagonists.

In summary, a large proportion of people using these drugs do not need them in the first place, given many nondrug and drug alternatives that should be tried first, especially for GERD. Even among those for whom PPI use is appropriate, efforts to curb needlessly prolonged use at doses unnecessarily high can be initiated.

The Gastrointestinal (GI) Tract and Gastroesophageal Reflux Disease (GERD)

The purpose of the gastrointestinal (GI) tract is to extract fluid and essential nutrients from the food we eat and to eliminate wastes. All the way along the tract, food is pushed by involuntary rhythmic muscular contractions called peristalsis. From the mouth, ingested food proceeds down a straight tube called the esophagus into the stomach. It is here that the process of digestion begins, with stomach acid being secreted to break down food. Enzymes that also facilitate the breakdown of chemicals in food, permitting absorption into the bloodstream, are secreted here and in subsequent sections of the GI tract. From the stomach, food passes into the small intestine, a relatively thin, long tube with three distinct portions: duodenum, jejunum and ileum. Enzymes from the pancreas and the gallbladder enter at the duodenum and have specific roles in the digestion of food. Generally several hours later, the remaining food passes from the ileum into the large intestine or colon. Water and some remaining nutrients are extracted in the large intestine, before the remains are excreted through the rectum as stool.

Most of the time, the GI tract functions without problems, but there are a number of ways in which the system can go awry. As mentioned, the stomach secretes acids to aid digestion. There is a sphincter at the junction between the esophagus and the stomach that is supposed to prevent these acidic stomach contents from backing up into the esophagus, which is not designed to tolerate such strong acids. When such regurgitation occurs, resulting in irritation of the esophagus, it can cause the chest pain or discomfort that is sometimes called gastroesophageal reflux disease (GERD) or heartburn, as well as nausea and an unpleasant taste in the mouth. The problem is typically worse after meals, when the stomach is full, and when lying down, because gravity no longer keeps the stomach contents in place.