From the Guidelines
Long-term use of proton pump inhibitors (PPIs) can cause several concerning side effects, including vitamin B12 deficiency, magnesium deficiency, increased risk of bone fractures, and higher susceptibility to certain infections, and therefore, patients on long-term PPI therapy should have regular monitoring and reassessment of the need for continued therapy 1.
Side Effects of Long-term PPI Use
The side effects of long-term PPI use are a concern due to the potential for nutrient deficiencies, increased risk of infections, and other systemic effects. Some of the common side effects include:
- Vitamin B12 deficiency
- Magnesium deficiency
- Increased risk of bone fractures
- Higher susceptibility to certain infections like Clostridium difficile and pneumonia
- Potential increased risk of chronic kidney disease, dementia, and stomach polyps with prolonged use
Recommendations for Minimizing Risks
To minimize the risks associated with long-term PPI use, the following recommendations can be made:
- Use PPIs at the lowest effective dose for the shortest duration necessary
- Regular monitoring of vitamin B12 and magnesium levels
- Consider calcium and vitamin D supplementation
- Periodic reassessment of the need for continued therapy
- Consider stepping down to H2 blockers like famotidine or ranitidine, or using PPIs on an as-needed or intermittent basis rather than daily
Importance of Regular Review and Documentation
Regular review and documentation of the ongoing indications for PPI use are essential to ensure that the benefits of therapy outweigh the potential harms 1. This review should be the responsibility of the patient’s primary care provider, and patients without a definitive indication for chronic PPI use should be considered for a trial of de-prescribing 1.
From the FDA Drug Label
Omeprazole delayed-release capsules can cause serious side effects, including: • A type of kidney problem (tubulointerstitial nephritis). • Diarrhea. • Bone fractures. • Certain types of lupus erythematosus.
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)
The side effects of long-term Proton Pump Inhibitor (PPI) use include:
- Kidney problems: such as tubulointerstitial nephritis
- Diarrhea: which may be caused by an infection (Clostridium difficile) in the intestines
- Bone fractures: particularly osteoporosis-related fractures of the hip, wrist, or spine, associated with long-term PPI therapy (a year or longer)
- Lupus erythematosus: including cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) 2 2
From the Research
Side Effects of Long-Term Proton Pump Inhibitor (PPI) Use
- Reduced intestinal absorption of vitamin B12 or calcium 3
- Increased rate of bone fractures 3, 4
- Interference with the metabolism of other drugs (e.g., clopidogrel) 3
- Increased incidence of Clostridium difficile-associated colitis 3, 5
- Acute interstitial nephritis 5
- Fractures 5, 4
- Clostridium difficile-associated diarrhea (CDAD) 5
- Salmonella and Campylobacter infections 6
- Gastric cancer 6
- Chronic renal failure via an interstitial nephritis mechanism 6
- Vitamin B12 and magnesium deficiency 6
- Osteoporosis 4
- Hypomagnesaemia 4
- Development of gastric polyps 4
- Enteric infections 4
- Pneumonia 4
Considerations for Long-Term PPI Use
- Patients should take the lowest effective dose 3, 7
- Long-term treatment with PPI requires repeated confirmation of a persisting indication 3
- PPI therapy as stress ulcer prophylaxis should be confined to risk groups and risk situations 3
- Patients on long-term therapy should be periodically evaluated for the indications for continued therapy 7, 4
- Deprescribing, defined as lowering dosage, switching to as-needed use, or complete discontinuation, should be considered for many PPI users 5