What is a significant concern with the long-term use of Proton Pump Inhibitors (PPIs), such as omeprazole (prilosec), in patients?

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Last updated: July 6, 2025View editorial policy

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From the Guidelines

Long-term use of Proton Pump Inhibitors (PPIs) is not safe due to potential harms, including pill burden, medication-related costs, and potential adverse effects related to long-term use, as stated in the 2022 expert review published in Gastroenterology 1. The primary concern with long-term PPI use is the potential for harm when there is no ongoing indication for the medication. Some key points to consider include:

  • Regular review of the ongoing indications for PPI use is essential to determine whether the potential benefits outweigh the potential harms 1.
  • Patients taking PPIs long-term may develop transient upper GI symptoms due to rebound acid hypersecretion when discontinuing the medication, as noted in the 2022 clinical practice update on de-prescribing of PPIs 1.
  • Long-term PPI use has also been associated with an increased risk of hepatic encephalopathy (HE) in patients with cirrhosis, as well as impaired absorption of micronutrients and increased hyponatraemia, highlighting the need for careful consideration of the benefit-risk balance in these patients 1. Therefore, it is crucial to regularly assess the need for continued PPI therapy and consider de-prescribing when there is no clear indication for ongoing use, as recommended by the 2022 expert review 1.

From the FDA Drug Label

Longer term data are needed to rule out the possibility of an increased risk of the development of gastric tumors in patients receiving long-term therapy with lansoprazole The FDA drug label does not directly answer the question of what is a significant concern with the long-term use of Proton Pump Inhibitors (PPIs). However, it mentions that longer term data are needed to assess the risk of gastric tumors in patients receiving long-term therapy with lansoprazole 2.

  • A significant concern with long-term use of PPIs is the potential increased risk of gastric tumors.
  • Enterochromaffin-like (ECL) cell effects, including hypergastrinemia, ECL cell proliferation, and formation of carcinoid tumors, have been observed in rat studies 2.
  • The label also notes that gastric biopsy specimens from patients treated with lansoprazole for at least one year did not show evidence of ECL cell effects similar to those seen in rat studies 2.

From the Research

Concerns with Long-Term Use of Proton Pump Inhibitors (PPIs)

  • A significant concern with the long-term use of PPIs is the potential for malabsorption of essential nutrients, such as vitamin B12 3.
  • Long-term use of PPIs has been associated with an increased risk of vitamin B12 deficiency, with a stronger association observed with higher doses 3.
  • Additionally, the use of acid-suppressive drugs, including PPIs, during pregnancy has been linked to an increased risk of childhood asthma 4.
  • However, it is essential to note that PPIs are generally considered safe for long-term treatment, with minimal side effects and few significant drug interactions 5.

Comparison with Histamine 2 Receptor Antagonists

  • PPIs have been shown to be more effective than histamine 2 receptor antagonists in preventing clinically important and overt upper gastrointestinal bleeding in critically ill patients 6.
  • However, the use of histamine 2 receptor antagonists at bedtime has been found to enhance nocturnal gastric pH control and decrease nocturnal gastric acid breakthrough in patients taking PPIs twice daily 7.

Safety in Pregnancy

  • While PPIs are generally considered safe, the use of acid-suppressive drugs during pregnancy has been associated with an increased risk of childhood asthma 4.
  • However, PPIs are often prescribed during pregnancy, and their safety profile is still being studied 4.

Administration and Efficacy

  • PPIs should be taken 30-60 minutes before food to maximize their efficacy 5.
  • PPIs have been shown to have superior gastric acid suppression compared to histamine 2 receptor antagonists 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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