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The number of PPI prescriptions written for patients leaving hospital dropped when guidelines were implemented. (iStockphoto)
The number of PPI prescriptions written for patients leaving hospital dropped when guidelines were implemented. (iStockphoto)

Medication

Ulcer meds linked to grave infections, fractures Add to ...

Proton pump inhibitors - drugs used to treat a range of digestive problems ranging from heartburn to bleeding ulcers - are among the most misused drugs on the market, new research concludes.

Between 53 per cent and 69 per cent of PPIs are inappropriately prescribed, particularly for dyspepsia, the medical term for indigestion and upset stomach. Proton pump inhibitors reduce the production of acid by blocking the enzyme in the stomach wall that produces it.

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"That PPIs relieve dyspepsia is without question, but at what cost - and I do not mean financial?" said Dr. Mitchell Katz, director of the San Francisco Department of Public Health, in an editorial published in Tuesday's edition of the Archives of Internal Medicine.

The journal features five articles examining the benefits and risks of PPIs, one of the top-selling categories of prescription drugs, with sales of more than $15-billion (U.S.) a year in North America alone.

Summarizing the evidence, Dr. Katz said that PPIs are effective in the treatment of gastroesophageal reflux disease (GERD), ulcers and other conditions such as ulcerative esophagitis, Barrett's esophagus, and Zollinger-Ellison syndrome, but are used too liberally for less serious conditions such as heartburn and indigestion.

"Harm will result if these commonly used medications are prescribed for conditions for which there is no benefit, such as non-ulcer dyspepsia," said Dr. Deborah Grady of the San Francisco Veterans Affairs Medical Center. She said risks seem particularly acute in seniors.

The potential harms are outlined in a series of studies published in the journal, including:

- A five-year study of 100,000 patients treated at Beth Israel Deaconess Medical Center in Boston that found patients taking proton pump inhibitors had a 74-per-cent greater risk of contracting Clostridium difficile, a severe bacterial infection;

- A study of 1,200 patients being treated for C. difficile at Boston Medical Center that found those taking PPIs had a 42-per-cent increased risk of a recurrence of the bacterial infection;

- An analysis of the Women's Health Initiative Study, which includes more than 160,000 women, that showed taking PPIs was associated with an increase in fractures, including fractures of the spine, forearm and the wrist, but not of the hip;

- A study at National Taiwan University College of Medicine in Taipei that found prescribing high doses of proton pump inhibitors for bleeding ulcers, a common treatment, did not reduce rates of bleeding, surgery or death in patients.

It is believed that taking PPIs may increase the risk of contracting the C. difficile because the drugs lower acidity in the stomach, which is one of the first lines of defence of the immune system, making it easier for bacterial spores to flourish. It's unclear why proton pump inhibitors may be tied to a higher risk of fractures, but the studies suggests it may be because the drugs also accelerate bone mineral loss.

Another paper published in the journal, however, offered a more positive take.

The research, led by Dr. Patrick Yachimski of Harvard Medical School, showed that implementing standardized guidelines - recommendations for physicians on when proton pump inhibitors should and should not be prescribed - sharply reduced misuse.

The study of 942 patients showed that the number of inpatients receiving PPIs fell to 16 per cent after guidelines were implemented, from 27 per cent before. At discharge, the prescription rate fell to 10 per cent from 16 per cent.

There are many brand-name and generic PPIs. The big sellers include esomeprazole (Nexium), lansoprazole (Prevacid) and pantoprazole (Pantoloc).

Heartburn and indigestion can be treated with over-the-counter acid neutralizers such as Tums, or with an earlier class of medication known as histamine-2 receptor antagonists (H2RAs) such as Zantac.

A study published earlier this year showed that, in Canada, use of PPIs has increased by 60 per cent over the past five years.

There were 33.5 million prescriptions for gastrointestinal medications in Canada last year, according to IMS Health Canada, a private company that tracks prescription drug sales. The retail value was almost $1.9-billion (Cdn.).

Follow on Twitter: @picardonhealth

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