From the Guidelines
Long-term omeprazole use, defined as more than one year of continuous use, can lead to several negative side effects, including increased risk of bone fractures, vitamin B12 deficiency, magnesium deficiency, and kidney problems, as evidenced by recent studies 1.
Key Side Effects
- Increased risk of bone fractures due to reduced calcium absorption, with a meta-analysis of 24 observational studies finding a 20% greater risk of hip fracture compared to controls 1
- Vitamin B12 deficiency, which can lead to neurological problems, with a large, nested case-control study finding a stronger association with vitamin B12 deficiency for mean daily PPI doses of >1.5 pills 1
- Magnesium deficiency, causing muscle cramps and irregular heartbeats, with a meta-analysis of 16 observational studies reporting a 71% higher risk of hypomagnesemia 1
- Kidney problems, including chronic kidney disease and acute interstitial nephritis, which may develop with long-term use
Additional Considerations
- Increased susceptibility to certain infections like Clostridium difficile and pneumonia
- Higher risks of developing dementia, though this connection requires more research
- Stomach polyps, usually benign, can occur with extended use
- Rebound acid hypersecretion when stopping the medication, making discontinuation difficult
- Interactions with other medications by altering stomach acidity and affecting the liver enzyme CYP2C19
Recommendations
- Patients on long-term therapy should have regular monitoring of vitamin B12, magnesium, and calcium levels
- Healthcare providers should discuss with patients whether continued use is necessary or if the lowest effective dose is being used, as the risks increase with duration of use 1
From the FDA Drug Label
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) 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. 5. 8 Hypomagnesemia Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. 5. 12 Fundic Gland Polyps PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year.
Long-term omeprazole use is defined as more than one year of continuous use. The negative side effects of long-term omeprazole use include:
- Bone fractures: Increased risk of osteoporosis-related fractures of the hip, wrist, or spine
- Cutaneous and systemic lupus erythematosus: Reported in patients taking PPIs, including omeprazole
- Cyanocobalamin (Vitamin B-12) deficiency: Malabsorption of cyanocobalamin caused by hypo- or achlorhydria
- Hypomagnesemia: Symptomatic and asymptomatic hypomagnesemia reported in patients treated with PPIs for at least three months
- Fundic gland polyps: Increased risk of fundic gland polyps that increases with long-term use, especially beyond one year 2
From the Research
Definition of Long-Term Omeprazole Use
Long-term omeprazole use is generally defined as more than one year of continuous use.
Negative Side Effects of Long-Term Omeprazole Use
Some of the negative side effects of long-term omeprazole use include:
- Increased risk of pneumonia 3
- Increased risk of Clostridium difficile infections 3
- Increased risk of fractures due to impaired magnesium absorption 3
- Thrombocytopenia, iron deficiency, vitamin B12 deficiency, rhabdomyolysis, and acute interstitial nephritis 3
- Vitamin B12 deficiency, especially in patients with Zollinger-Ellison syndrome 4
- Decreased serum vitamin B12 levels in elderly patients 5
- Vitamin B12 malabsorption, particularly in patients with poor dietary intake of vitamin B12, impaired vitamin B12 stores, and certain gastrointestinal disorders 6
Specific Studies on Long-Term Omeprazole Use
- A study published in 2013 found that long-term use of proton pump inhibitors, including omeprazole, was associated with an increased risk of serious adverse effects 3.
- A study published in 1998 found that long-term treatment with omeprazole altered serum vitamin B12 levels in patients with Zollinger-Ellison syndrome 4.
- A study published in 2021 found that prolonged acid suppression therapy with proton pump inhibitors or H2 blockers may result in serum vitamin B12 deficiency in elderly patients 5.
- A study published in 1999 found that omeprazole therapy decreased the absorption of vitamin B12, but the clinical significance of this effect was unclear 6.
- A study published in 2007 found that long-term use of proton pump inhibitors, including omeprazole, was generally safe in children, but few adverse reactions were reported 7