What are the effects of long-term omeprazole (proton pump inhibitor) use?

From the Guidelines

Long-term omeprazole use should be limited to the shortest duration necessary for symptom control, typically not exceeding 4-8 weeks without medical supervision. For those requiring extended therapy, the lowest effective dose should be used, often 20mg daily for maintenance. Patients on long-term omeprazole should have regular medical follow-ups every 6-12 months to reassess the need for continued treatment. Potential risks of prolonged use include vitamin B12 and magnesium deficiencies, increased risk of bone fractures, kidney problems, and higher susceptibility to certain infections like C. difficile. To minimize these risks, consider periodic "drug holidays" under medical supervision, take the medication 30-60 minutes before breakfast, supplement with vitamin B12 and magnesium if needed, and maintain adequate calcium and vitamin D intake. Long-term omeprazole works by irreversibly binding to proton pumps in the stomach, reducing acid production, which effectively manages conditions like GERD and peptic ulcers but can alter normal digestive processes when used chronically, hence the need for monitoring and periodic reassessment.

Some key points to consider when using omeprazole long-term include:

• The risk of adverse cardiovascular outcomes when combined with clopidogrel, particularly in patients with impaired CYP2C19 function 1
• The potential for decreased efficacy of clopidogrel when used with omeprazole, due to inhibition of CYP450 2C19 1
• The importance of weighing the benefits and harms of continued PPI use, particularly in patients with a history of severe erosive esophagitis or GERD-related complications 1
• The need for regular monitoring and follow-up to reassess the need for continued treatment and minimize potential risks 1

Overall, while omeprazole can be an effective treatment for conditions like GERD and peptic ulcers, its long-term use requires careful consideration and monitoring to minimize potential risks and ensure optimal outcomes.

From the FDA Drug Label

It is not known if omeprazole delayed-release capsules are safe and effective when used for longer than 12 months (1 year) for this purpose. For the long-term treatment of conditions where your stomach makes too much acid. The long-term use of omeprazole is not well established, and it is not known if it is safe and effective for use longer than 12 months. However, it can be used for the long-term treatment of conditions where the stomach makes too much acid, such as Zollinger-Ellison Syndrome. 2

From the Research

Long-term Omeprazole Treatment

• The effectiveness and safety of long-term omeprazole treatment have been studied in various patient populations, including those with Zollinger-Ellison syndrome 3 and gastroesophageal reflux disease (GERD) 4, 5.
• In patients with Zollinger-Ellison syndrome, omeprazole 20 mg/day was successful as initial therapy in 68% of patients, while the remaining 32% required higher doses 3.
• Long-term omeprazole therapy (up to 11 years) has been shown to be highly effective and safe for controlling reflux esophagitis in patients with GERD 4.
• However, long-term use of proton pump inhibitors (PPIs), including omeprazole, has been linked to an increased risk of osteoporosis and osteoporotic fractures 6, 7.

Safety and Efficacy

• Omeprazole has been shown to have a good long-term safety profile, with an adverse event profile similar to that expected in an elderly population 4.
• The efficacy of omeprazole in maintaining remission in patients with reflux oesophagitis has been demonstrated in several studies, with 82% of patients remaining in endoscopic and symptomatic remission over a period of 12 months 5.
• However, the use of PPIs, including omeprazole, has been associated with an increased risk of osteoporosis, particularly with long-term use 6, 7.

Mechanisms and Risks

• The mechanism by which PPIs, including omeprazole, increase the risk of osteoporosis is not fully understood, but may involve alterations in calcium and magnesium levels, as well as effects on bone cell proliferation and differentiation 7.
• The TRPM7 channel has been identified as a potential mediator of the effects of PPIs on bone remodeling, with pantoprazole treatment reducing expression of this channel in bone cells 7.
• The risk of osteoporosis associated with long-term PPI use highlights the importance of using the lowest effective dose and monitoring patients for signs of osteoporosis 6, 7.