From the Guidelines
Proton pump inhibitors (PPIs) can cause several side effects, including diarrhea, gastrointestinal infections, and magnesium deficiency, and patients experiencing these side effects should consider switching to alternative treatments under the guidance of a healthcare provider 1.
Common Side Effects of PPIs
The use of PPIs has been associated with various side effects, ranging from mild to severe. Common short-term side effects include:
- Headache
- Nausea
- Abdominal pain
- Flatulence
- Diarrhea
- Constipation These side effects typically resolve on their own but can be bothersome for some patients.
Serious Concerns with Long-term PPI Use
Long-term use of PPIs may lead to more serious concerns, such as:
- Vitamin B12 deficiency
- Magnesium deficiency
- Increased risk of bone fractures
- Kidney problems
- Increased susceptibility to certain infections like Clostridium difficile and pneumonia These risks are particularly important to consider in patients with underlying health conditions or those taking other medications that may interact with PPIs.
Mechanism of Action and Side Effects
PPIs work by blocking acid production in the stomach, which can disrupt normal digestive processes and nutrient absorption. This mechanism of action can lead to an increased risk of certain side effects, particularly with long-term use. For example, the increased gastric pH can promote microbial proliferation and dysbiosis in the small intestine, leading to the formation of products like ammonia and bacterial endotoxins 1.
Management of Side Effects
If patients experience troublesome side effects from PPIs, they should not stop taking the medication abruptly. Instead, they should consult their healthcare provider about potential dose adjustments, switching to a different PPI, or considering alternative treatments like H2 blockers (ranitidine, famotidine) which may have fewer side effects for some individuals. It is essential to weigh the benefits and risks of PPI use and to regularly reassess the need for continued treatment 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.
The side effects of Proton Pump Inhibitors (PPIs), such as omeprazole, include:
- Kidney problems: Tubulointerstitial nephritis, which can occur at any time during treatment.
- Diarrhea: Increased risk of severe diarrhea, which may be caused by an infection (Clostridium difficile) in the intestines.
- Bone fractures: Increased risk of fractures of the hip, wrist, or spine, especially with long-term use.
- Lupus erythematosus: Certain types of lupus erythematosus, including cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). 2 2
From the Research
Side Effects of Proton Pump Inhibitors (PPIs)
- Increased susceptibility to infections, such as pneumonia and Clostridium difficile infection, has been associated with PPI use 3, 4, 5
- Secondary hypergastrinaemia, which can lead to rebound acid hypersecretion following discontinuation of treatment, is a potential side effect of long-term PPI use 3
- Impeded absorption of micronutrients, including iron, vitamin B12, and magnesium, has been reported with PPI use 6, 5
- Idiosyncratic reactions, such as thrombocytopenia, rhabdomyolysis, and acute interstitial nephritis, have been associated with PPI use 5
- Increased risk of bone fractures and osteoporosis has been reported with long-term PPI use 4, 6, 5
- Cardiovascular diseases, gastrointestinal malignancies, and chronic kidney diseases have been linked to increased mortality in patients taking PPIs 4
Patient and Physician Perspectives
- Patients are often informed about PPI side effects from non-physician sources, and may change their behavior based on these concerns without physician input 6
- Physicians may also change their practice based on concerns about PPI-related adverse events, despite the level of evidence being low 4, 6
- Patients and physicians are concerned about the potential side effects of PPIs, including bone fractures, osteoporosis, and increased risk of infections 6
Adverse Events and Mortality
- Recent studies have reported an increased risk of mortality linked to cardiovascular diseases, gastrointestinal malignancies, and chronic kidney diseases in patients taking PPIs 4
- The level of evidence on adverse events is low, and most findings have not been confirmed in clinical trials 4
- PPI overuse and off-label prescriptions must be eradicated, but long-term PPI use for clear indications must continue until stronger evidence is available 4