From the Guidelines
Prolonged use of Proton Pump Inhibitors (PPIs) can lead to potential long-term harms, and patients should have a regular review of the ongoing indications for use and documentation of that indication, as recommended by the American Gastroenterological Association (AGA) in 2022 1. The potential long-term harms of PPI use include:
- Increased risk of bone fractures due to reduced calcium absorption
- Vitamin B12 deficiency leading to neurological problems
- Increased risk of certain infections like C. difficile and pneumonia
- Kidney problems including chronic kidney disease
- Potential increased risk of dementia and heart attacks, though evidence for these latter concerns is less conclusive
- Magnesium deficiency
- Increased risk of stomach polyps It is essential to weigh these potential harms against the benefits of PPI use, particularly for patients with clear medical indications, such as complicated gastroesophageal reflux disease or known Barrett’s esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis, who should generally not be considered for PPI discontinuation 1. Patients taking PPIs long-term should consider periodic reassessment with their doctor to determine if continued use is necessary, and possibly try the lowest effective dose or switch to on-demand therapy, as suggested by the AGA in 2022 1. Some patients may benefit from alternative medications, such as H2 blockers like famotidine, which can help reduce acid production in the stomach while minimizing the risks associated with long-term PPI use. It is crucial to note that the decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for potential adverse events associated with PPI use, as stated in the AGA clinical practice update in 2022 1.
From the FDA Drug Label
5.4 Bone Fracture Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer) 2 5.4 Bone Fracture Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer) 3 5.4 Bone Fracture Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer) 4 The potential long-term harms of prolonged Proton Pump Inhibitor (PPI) use include:
- Increased risk of osteoporosis-related fractures of the hip, wrist, or spine, especially with high-dose and long-term therapy
- Clostridium difficile-associated diarrhea, especially in hospitalized patients
- Cutaneous and systemic lupus erythematosus, which may occur as new onset or exacerbation of existing autoimmune disease
- Cyanocobalamin (Vitamin B-12) deficiency, which may occur with long-term use of acid-suppressing medications
- Hypomagnesemia, which may occur with long-term use of PPIs, especially in patients taking medications that may cause hypomagnesemia It is recommended to use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
From the Research
Potential Long-term Harms of Prolonged Proton Pump Inhibitor (PPI) Use
The potential long-term harms of prolonged PPI use include:
- Reduced intestinal absorption of vitamin B12 or calcium 5
- Increased rate of bone fractures 5, 6
- Interference with the metabolism of other drugs (e.g., clopidogrel) 5, 6
- Increased incidence of Clostridium difficile-associated colitis 5
- Hypomagnesemia 6
- Gastrointestinal infections 7
- Pneumonia 7
- Nutrient deficiencies 7
- Spontaneous bacterial peritonitis 7
- Small intestinal bacterial overgrowth 7
- Allergic reactions 7
- Acute interstitial nephritis 7
- Chronic kidney disease 7
- Poor cardiovascular outcomes 7
- Dementia 7
- Drug interactions 7
Strategies for Minimizing Long-term Harms
To minimize the long-term harms of PPI use, the following strategies can be employed:
- Use the lowest effective dose of PPIs 8, 5, 6
- Limit the duration of PPI use to the minimum necessary 8, 5, 6
- Consider alternative treatments, such as alginate rescue therapy, for patients who require long-term PPI use 9
- Monitor patients for signs of adverse effects, such as hypomagnesemia 6
- Educate patients and providers about the potential risks and benefits of PPI use 7
- Consider deprescribing PPIs in patients who no longer require them 9, 7