From the Guidelines
Proton pump inhibitors (PPIs) like omeprazole, esomeprazole, pantoprazole, and lansoprazole commonly cause several side effects with daily use, including headache, nausea, abdominal pain, constipation, flatulence, and diarrhea, as reported in a 2022 study 1. The most frequent side effects of PPIs include:
- Headache
- Nausea
- Abdominal pain
- Constipation
- Flatulence
- Diarrhea Some people may also experience dry mouth, dizziness, or skin rashes. These medications work by reducing stomach acid production by blocking the proton pump in gastric parietal cells, which helps treat conditions like GERD, peptic ulcers, and gastritis, but this acid reduction can lead to reduced absorption of nutrients like vitamin B12, magnesium, calcium, and iron with long-term use, as noted in a 2022 expert review 1. PPIs may also increase the risk of intestinal infections like C. difficile since stomach acid normally helps kill ingested bacteria. If you experience severe or persistent side effects, contact your healthcare provider, but don't stop taking PPIs abruptly as this can cause rebound acid hypersecretion, as advised in a 2022 clinical practice update 1. Most side effects are mild and often improve after the first few weeks of treatment as your body adjusts to the medication. It is essential to follow the recommended dosage and consult your healthcare provider before making any changes to your medication regimen, as higher-dose PPIs have been associated with increased costs and potential complications, such as community-acquired pneumonia, hip fracture, and Clostridium difficile infection, as reported in a 2022 study 1.
From the FDA Drug Label
5.2 Acute Tubulointerstitial Nephritis Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. 5.3 Clostridium difficile-Associated Diarrhea Published observational studies suggest that PPI therapy like omeprazole may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. 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. 5.5 Cutaneous and Systemic Lupus Erythematosus Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including omeprazole. 5.7 Cyanocobalamin (Vitamin B-12) Deficiency Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria.
The everyday side effects of taking a Proton Pump Inhibitor (PPI) like omeprazole or lansoprazole may include:
- Acute Tubulointerstitial Nephritis: a rare but serious side effect that can occur at any point during PPI therapy 2
- Clostridium difficile-Associated Diarrhea: an increased risk of diarrhea, especially in hospitalized patients 2
- Bone Fracture: an increased risk for osteoporosis-related fractures of the hip, wrist, or spine, especially with long-term use 2
- Cutaneous and Systemic Lupus Erythematosus: a rare but serious side effect that can occur with PPI use 2
- Cyanocobalamin (Vitamin B-12) Deficiency: a potential side effect of long-term acid-suppressing therapy 2 3
- Hypomagnesemia: a rare but serious side effect that can occur with long-term PPI use, especially with concomitant use of certain medications 3
From the Research
Everyday Side Effects of PPIs
The everyday side effects of Proton Pump Inhibitors (PPIs) are a subject of interest due to their widespread use in treating acid-related disorders.
- According to 4, PPIs are generally considered safe, but there have been reports of potential adverse effects associated with their long-term use.
- A study by 5 found that the risk of pneumonia was increased by 27-39% in short-term use of PPIs, and C. difficile infections were also associated with the use of PPIs.
- Additionally, 5 reported that thrombocytopenia, iron deficiency, vitamin B12 deficiency, rhabdomyolysis, and acute interstitial nephritis have also been associated with the use of PPIs.
Common Side Effects
Some common side effects of PPIs include:
- Enteric infection, as reported by 4
- Pneumonia, with a 27-39% increased risk in short-term use, as found by 5
- C. difficile infections, with an odds ratio of 2.15, as reported by 5
- Thrombocytopenia, iron deficiency, vitamin B12 deficiency, rhabdomyolysis, and acute interstitial nephritis, as mentioned by 5
Comparison of PPIs
Different PPIs may have varying side effect profiles due to their distinct pharmacokinetic and pharmacodynamic properties.
- A study by 6 discussed the differences in the physicochemical properties of PPIs, which may impact their clinical performance and side effect profiles.
- Another study by 7 compared the pharmacokinetics, pharmacodynamics, and clinical efficacy of different PPIs, including lansoprazole, omeprazole, pantoprazole, and rabeprazole.
- 8 summarized the published data on lansoprazole, a PPI approved for use in treating duodenal ulcer, erosive esophagitis, and pathologic hypersecretory conditions.