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Judicious PPI use necessary to avoid serious adverse events
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A recent review article detailed the potential harms associated with use of proton pump inhibitors, concluding that physicians should follow Health Canada’s recommendations that the drugs “should be prescribed at the lowest dose and shortest duration of therapy appropriate to the condition being treated.”
“Proton pump inhibitors are associated with a number of rare but potentially serious adverse effects,” the authors wrote. “These uncommon effects become highly relevant when considering the tens of millions of patients who take PPIs worldwide. Recognizing some of these harms, the [FDA] and Health Canada have issued safety advisories regarding the use of PPIs related to Clostridium difficile, fracture risk and profound hypomagnesemia.”
The review breaks down these rare adverse events into three categories — drug interactions, and noninfectious and infectious complications — but emphasizes that because the available evidence is limited to observational studies, their results show associations and not necessarily causation.
Drug interactions
According to the review, the drug-drug interaction between PPIs and Plavix (clopidogrel, Bristol-Myers Squibb, Sanofi) may be “the most highly debated,” with multiple studies reporting conflicting data on the associated risk for myocardial infarction resulting from concurrent use of the drugs. While the debate is currently focused on PPI use as a marker for at-risk patients rather than being causally associated with myocardial infarction, the FDA has still suggested that concomitant use of Nexium (esomeprazole, AstraZeneca) or Prilosec (omeprazole, Procter & Gamble) with clopidogrel should be avoided.
Other drugs that have the potential for interactions with PPIs, especially omeprazole, include thyroid hormone replacement drugs, chemotherapy drugs, antifungals and antiretroviral agents, they wrote.
Noninfectious, infectious complications
The most important noninfectious adverse events associated with PPIs, according to the review, include rebound acid hypersecretion after PPI discontinuation, malabsorption of vitamin B12, iron and magnesium, osteoporosis, acute interstitial nephritis, dementia and functional decline.
Moreover, the most important infectious complications include diarrhea associated with C. difficile and other enteric infections, pneumonia and, among patients with cirrhosis and ascites, spontaneous bacterial peritonitis. The AASLD has therefore recommended that “PPIs should be used with caution in patients with cirrhosis and be reserved for an appropriate duration of therapy in patients with peptic ulcer disease, or for a short period following esophageal variceal ligation.”
Using PPIs judiciously
Further studies are needed to identify efficient strategies for limiting and tapering inappropriate PPI prescriptions, though some that have been developed so far include a web-based educational intervention for medical residents to assess appropriateness of PPI prescriptions, and a nurse-led action plan for ceasing unnecessary PPI use.
The authors advise physicians to adhere to the tenets of the Choosing Wisely Canada campaign, which recommends that “new PPI prescriptions ought to be for evidence-based indications, continuous PPI use should be re-evaluated regularly, and patients should be counseled on possible complications when contemplating long-term therapy.” – by Adam Leitenberger
Disclosures: The researchers reports no relevant financial disclosures.
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