The review deals with the data on negative health impact of prolonged and inadequate use of proton pump inhibitors (PPI). Since their advent at the end of 1980s, their worldwide use has been continuously increasing. However, up to 70% of PPI use is not based on clear indications. Inadequate treatment with PPI not complying with clinical guidelines results in a higher risk of adverse events, especially in the elderly. Prolonged (more than 8 weeks) intake of PPI increases the risk of osteoporotic fractures, promotes Clostridioides difficile infection and gut microbiota abnormalities, community-acquired pneumonia, vitamin B12 deficiency, renal disease, dementia, risk of gastric cancer, etc. Most potential side effects of PPI are the results of hypochlorhydria and reflex hypergastrinemia. The main safety principle for PPI is adherence to short duration of treatment and minimally effective doses. Rational strategies for safe and effective PPI treatment are supported by the evidence-based deprescribing in gastroesophageal reflux disease and include dose tapering or therapy as needed after the treatment course for a specific indication has been finished, or stopping the treatment in patients with no adequate indications to PPI administration. Increased awareness of medical personnel and patients on the proper PPI use and their side effects would make it possible to optimize the use of these agents in the real world medical practice.
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