Proton pump inhibitors

  Almost £2bn (US$3.9bn) worldwide is being spent unnecessarily each year on indigestion drugs, accord-ing to a recent editorial published in the British Medical Journal (BMJ, 2008; 336: 2–3).

The report highlights the impact of such overprescribing on drug budgets around the globe, but the real problem could be what this means for the millions of patients taking these drugs, as they are linked to a number serious adverse effects. 

Proton pump inhibitors (PPIs), which stop the backflow of stomach acid up into the oesophagus, are among the most commonly prescribed classes of drugs in the world.

In 2006 alone, spending on these drugs was £425m in England and £7bn globally. Yet, up to 70 per cent of patients taking the drug have no appropriate indication, states the BMJ article, so billions of pounds are being wasted on pointless prescriptions every year. 

The authors of the report, Drs Ian Forgacs and Aathavan Logana-yagam, both from King’s College Hospital in London, argue that healthcare professionals are ignoring prescribing guidelines by doling out PPIs far too readily, even though less expensive alter-natives, such as H2-receptor antagonists, are available.

In the UK, PPI prescriptions have superseded those for all other acid-inhibiting agents and now account for more than 90 per cent of the National Health Service (NHS) medicines budget for treating dyspepsia (indigestion). If prescriptions were restricted to the recommended guidelines—which are, in fact, rather selec-tive—PPI expenditure would be far less, say Forgacs and Loganaya-gam.

Moreover, the two authors claim that “evidence of inappropriate use of PPIs in secondary care is abundant”. Indeed, studies of hospital inpatients in Australia, Ireland and the UK show that 33–67 per cent of those taking PPIs do not meet their country’s criteria for taking the drug (J Clin Pharm Ther, 2000; 25: 333–40; Int J Clin Pract, 2005; 59: 31–4; Pharm World Sci, 2001; 23: 116–7).

In the US, a study of hospital inpatients in Michigan found that 29 per cent of patients were taking a PPI at the time of admission, and another 42 per cent were prescribed the drug in hospital. At discharge, more than half the patients were taking a PPI—nearly twice the number taking these drugs when admitted. Say the researchers, 90 per cent of patients should not have been taking these drugs, revealing “considerable excess usage of acid suppressants in both the inpatient and outpatient settings” (Ann Pharmacother, 2006; 40: 1261–6).

 

A ‘just-in-case’ drug

So, what is the reason for this inappropriate and overuse of PPIs? Say Forgacs and Loganayagam, it’s because the drugs have a reputation for combining a high level of efficacy with low toxicity. In other words, the drugs are thought to be safe and effective, so many doctors prescribe them as a ‘just-in-case’ treatment. 

Not surprisingly, however, the drugs aren’t as benign as doctors would have us believe. In recent years, they’ve been linked to an increase in Campylobacter infect-ions of the stomach and gastro-intestinal tract, as well as a doubling of the risk of infection with Clostridium difficile (BMJ, 1996; 312: 414–5; JAMA, 2005; 294: 2989–95). The reason for this is that PPIs block the production of gastric acid, the body’s natural defence against bacteria, leaving the patient more vulnerable to intestinal infections.

The drugs have also been associated with an increased risk of community-acquired pneumonia. One study found the risk to be especially high for patients who had only recently started the PPI treatment (Arch Intern Med, 2007; 167: 950–5).

Yet another adverse effect appears to be osteoporosis. A study involving nearly 150,000 patients found that long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture (JAMA, 2006; 296: 2947–53). This is worrying as Forgacs and Logana-yagam’s editorial notes that a significant number of patients are needlessly taking PPI’s over long periods of time, often without a date being set for review of their prescription (BMJ, 2008; 336: 2–3).

PPI use is questionable even in patients for whom the drugs are indicated—such as those suffering from gastro-oesophageal reflux disease (GORD, or GERD in the US). Research shows that nearly 30 per cent of such patients continue to suffer from symptoms despite taking the drugs—so  much for their efficacy (Minerva Gastroenterol Dietol, 2003; 49: 277–87).

Clearly, there is little evidence to justifiy the massive overprescribing of proton pump inhibitors.

For alternative ways to manage and treat GORD/GERD, see WDDTY vol 18 no 4.

Joanna Evans

 

Other PPI side-effects

 

-           Nausea

-            Vomiting

-            Constipation

-            Diarrhoea

-            Abdominal pain

-            Dizziness

-           Rash

-           Cough

-           Back pain

-            Headache.