What are the risks and management strategies for chronic Proton Pump Inhibitor (PPI) use?

From the Guidelines

Chronic proton pump inhibitor (PPI) use should be limited to the shortest duration necessary at the lowest effective dose due to potential long-term risks, as recommended by the most recent guidelines 1.

Risks Associated with Chronic PPI Use

The risks associated with chronic PPI use include increased fracture risk due to calcium malabsorption, vitamin B12 deficiency, hypomagnesemia, increased risk of Clostridium difficile infections, community-acquired pneumonia, and potential kidney injury, as highlighted in recent studies 1.

Management Strategies

To manage these risks, clinicians should:

• Regularly reassess the need for continued therapy, considering step-down approaches (reducing dose or switching to H2 blockers like famotidine 20mg twice daily) and implementing drug holidays when appropriate, as suggested by the AGA clinical practice update 1.
• Provide patients with standardized educational material on GERD mechanisms, weight management, lifestyle and dietary behaviors, relaxation strategies, and awareness about the brain-gut axis relationship, as recommended by the AGA clinical practice update on the personalized approach to the evaluation and management of GERD 1.
• Emphasize lifestyle modifications, including weight loss, avoiding trigger foods, elevating the head of the bed, and not eating within 3 hours of bedtime, which may reduce or eliminate the need for continuous PPI therapy in some patients.
• Consider supplementation with calcium citrate (rather than calcium carbonate) to improve absorption in patients at risk for fractures, as suggested by studies on the adverse effects of medications on micronutrient status 1.
• Monitor patients on long-term PPIs periodically for magnesium, vitamin B12, and bone density, especially in high-risk populations, as recommended by the AGA clinical practice update 1.

Key Recommendations

The decision to discontinue PPIs should be based solely on the lack of an indication for PPI use, and not because of concern for potential adverse effects, as stated in the AGA clinical practice update 1. Patients who discontinue long-term PPI therapy should be advised that they may develop transient upper gastrointestinal symptoms due to rebound acid hypersecretion, and clinicians should be prepared to manage these symptoms accordingly, as recommended by the AGA clinical practice update 1. Overall, a personalized approach to the evaluation and management of GERD, taking into account the individual patient's needs and risks, is essential for minimizing the risks associated with chronic PPI use, as emphasized by the AGA clinical practice update on the personalized approach to the evaluation and management of GERD 1.

From the FDA Drug Label

5.1 Presence of Gastric Malignancy 5.2 Acute Tubulointerstitial Nephritis 5.3 Clostridium difficile-Associated Diarrhea 5.4 Bone Fracture 5.5 Cutaneous and Systemic Lupus Erythematosus 5.6 Interaction with Clopidogrel 5.7 Cyanocobalamin (Vitamin B-12) Deficiency

The risks associated with chronic PPI usage include:

• Acute Tubulointerstitial Nephritis: a kidney problem that can occur at any time during treatment with PPIs 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, particularly with high-dose and long-term PPI therapy 2
• Cutaneous and Systemic Lupus Erythematosus: a risk of developing certain types of lupus erythematosus or worsening of existing lupus 2
• Cyanocobalamin (Vitamin B-12) Deficiency: a risk of malabsorption of cyanocobalamin (vitamin B-12) with long-term use of acid-suppressing medications 2 Management strategies for chronic PPI use include:
• Using the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated 2
• Considering alternative anti-platelet therapy when using omeprazole with clopidogrel 2
• Monitoring for signs and symptoms of CLE or SLE and discontinuing the drug if they occur 2
• Evaluating patients with suspected acute TIN and discontinuing the drug if necessary 2

From the Research

Risks of Chronic PPI Usage

• Long-term use of Proton Pump Inhibitors (PPIs) is associated with several adverse drug events, including acute interstitial nephritis, fractures, and Clostridium difficile-associated diarrhea (CDAD) 3.
• PPI use may be associated with an increased risk of adverse kidney events, especially in the elderly, with long-term PPI use and pre-existing kidney disease 4.
• There are also reports of intestinal infections, including Clostridium difficile, besides poor vitamins absorption and minerals such as vitamin B12, magnesium, and iron 4.
• Additionally, there are some dementia, pneumonia, kidney disease, myocardial infarction, and stroke reports associated with long-term PPI use 4.

Management Strategies for Chronic PPI Use

• Patients with GERD and acid-related complications should take a PPI for short-term healing, maintenance of healing, and long-term symptom control 5.
• Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them 5.
• The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition 5.
• Deprescribing, defined as lowering dosage, switching to as-needed use, or complete discontinuation, should be considered for many PPI users 3.
• Alternative therapy considerations include histamine-2-receptor antagonists, as they are found to be associated with reduced CDAD and fracture events 3.
• Lifestyle modifications, such as weight loss, upright head of bed elevation, avoiding meals close to bedtime, and avoiding high-fat meals within two to three hours of reclining, can help reduce the potential rebound hypersecretion that may occur as a result of discontinuation 3.

Best Practices for PPI Use

• PPIs should be used at the lowest dose and for the shortest duration possible 6.
• PPIs are still relatively well-tolerated drugs but should only be prescribed for proven indications 6.
• Long-term PPI users should not routinely use probiotics to prevent infection, raise their intake of calcium, vitamin B12, or magnesium beyond the Recommended Dietary Allowance (RDA), or screen or monitor bone mineral density, serum creatinine, magnesium, or vitamin B12 5.
• Specific PPI formulations should not be selected based on potential risks 5.