Introduced in the 1970s for use in reducing gastric acid production, proton pump inhibitors (PPIs) are among the most widely sold drugs in the world; omeprazole appears on the World Health Organization Model List of Essential Medicines. They are used in treating conditions such as gastroesophageal reflux disease (GERD), dyspepsia, reflux esophagitis, peptic ulcer disease (PUD), and hypersecretory conditions (e.g., Zollinger-Ellisson Syndrome), and are included as part of the eradication therapy for Helicobacter pylori bacteria (Cochrane Database of Systematic Reviews 2015, Issue 11. Art. No. CD011969. doi: 10.1002/14651858.CD011969).
Explore this issue:October 2016
PPIs are also commonly used on a long-term basis for preventing esophagitis caused by laryngopharyngeal reflux (LPR). PPIs are effective at reducing gastric acid, but researchers have noted the potential for harm that comes from long-term prescription-level use, including an increased risk of bone fractures not found with short-term, low-dose use. The U.S. Food and Drug Administration included a warning on PPI drug labels in 2010, noting that the available data show that patients at the highest risk for fractures received high doses of prescription PPIs and/or used a PPI for one year or more, but decided against adding a warning label to over-the-counter versions.
Alongside an increase in bone fracture risk, long-term high-dose PPIs carry other risks, including the possibility of interference with the absorption of iron, calcium, magnesium and vitamin B-12 due to a reduction in the breakdown of micronutrients released by gastric acid (Curr Gastroenterol Rep. 2010;12: 448–457). Long-term use has also been associated with an increased risk of pneumonia and Clostridium difficile colitis, according to the Cochrane Report.
This raises an important question for clinicians who see patients with LPR: How do you assess whether a patient should be on PPIs on a long-term basis, and how do you wean them off of the medication if necessary?
As PPI use becomes ever more common, it is important to note that some patients may not need them as part of a regular regimen—a recent study noted that up to 50% of PPI users are inappropriately prescribed the medication (Ann Pharmacother. 2015;49:29-38).
Part of the problem is that while LPR symptoms differ from GERD symptoms in that LPR doesn’t usually include heartburn and regurgitation, the symptoms that are most frequently reported in LPR (mild hoarseness and the need to clear the throat, globus, post-nasal drip, chronic cough, difficulty swallowing, sore throat, and an irritated, swollen larynx) are nonspecific and may be due to other factors such as allergy, smoking, environmental irritants, infection, or vocal abuse (Am J Otolaryngol. 2016;37:245-250). The researchers who conducted the study reported on in Annals of Pharmacotherapy also noted that 22% to 70% of patients who are prescribed a PPI do not have an appropriate indication for it.