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

Risks and Management Strategies for Long-Term PPI Use

Long-term PPI use should be limited to patients with definitive indications, and all other patients should be considered for deprescribing due to potential adverse effects including increased risk of community-acquired pneumonia, hip fracture, Clostridium difficile infection, and other complications. 1

Risks Associated with Long-Term PPI Use

Long-term PPI therapy carries several potential risks that should be weighed against benefits:

• Medication burden and costs: Unnecessary pill burden and financial costs 1
• Increased risk of infections:
  • Clostridium difficile-associated diarrhea 1, 2
  • Community-acquired pneumonia 1
• Bone health concerns: Increased risk of hip fractures 1
• Other potential concerns:
  • Acute interstitial nephritis 2
  • Hypomagnesemia 2
  • Vitamin B12 deficiency
  • Cutaneous and systemic lupus erythematosus 2
  • Interference with diagnostic investigations for neuroendocrine tumors (increased CgA levels) 2
  • Drug interactions with medications like methotrexate, antiretrovirals, and warfarin 2

It's important to note that while observational studies have suggested these associations, randomized controlled trials comparing PPIs with placebo have not consistently shown higher rates of adverse events among PPI users 1.

Appropriate Indications for Long-Term PPI Use

PPIs should only be continued long-term for specific indications:

Definitely Indicated for Long-Term Use (>8 weeks) 1:

• Barrett's esophagus
• Clinically significant (LA Classification grade C/D) erosive esophagitis
• Gastroprotection in high-risk NSAID/ASA users
• Secondary prevention of gastric/duodenal ulcers without concomitant antiplatelet drugs

Conditionally Indicated for Long-Term Use 1:

• PPI-responsive endoscopy-negative reflux disease with recurrence on cessation
• Esophageal strictures from GERD
• Prevention of progression of idiopathic pulmonary fibrosis

Management Strategy for Long-Term PPI Users

Step 1: Review Indication and Document

All patients taking a PPI should have regular review of the ongoing indications for use and clear documentation of that indication 1. This should be the responsibility of the primary care provider.

Step 2: Assess Need for Continued Use

Determine if the patient has a definitive indication for chronic PPI use. If not, consider a trial of deprescribing 1.

Step 3: Consider Dose Reduction

For patients with an indication for chronic PPI use who take twice-daily dosing, consider stepping down to once-daily PPI 1. Higher-dose PPIs increase costs and have been more strongly associated with complications.

Step 4: Deprescribing Algorithm for Those Without Clear Indications

1. Assess upper GI bleeding risk before deprescribing 1

   • Patients at high risk should not be considered for PPI deprescribing

2. Choose deprescribing method 1, 3

   • Either dose tapering or abrupt discontinuation can be considered
   • Tapering may be preferred as it could lead to higher success rates in discontinuation 3

3. Advise patients about rebound symptoms 1

   • Inform patients they may develop transient upper GI symptoms due to rebound acid hypersecretion
   • Reassure that symptoms typically resolve within 2-4 weeks

4. Follow-up and monitoring

   • Regular follow-up to assess symptom recurrence
   • Consider on-demand therapy for patients with non-erosive GERD 1

Step 5: Patient Education and Shared Decision Making

Patients value symptom control highly and worry about symptoms returning if the PPI is reduced 4. They are more likely to consider reducing their PPI if:

• A clinician provides advice and education
• They understand the rationale for deprescribing
• They know what to expect from deprescribing
• They are reassured they can return to their previous dose if necessary 4

Special Considerations

Patients Who Should NOT Be Considered for PPI Discontinuation 1:

• Complicated GERD (severe erosive esophagitis, esophageal ulcer, peptic stricture)
• Barrett's esophagus
• Eosinophilic esophagitis
• Idiopathic pulmonary fibrosis
• High risk for upper GI bleeding

Monitoring Recommendations

• Long-term PPI users do not routinely need to screen or monitor bone mineral density, serum creatinine, magnesium, or vitamin B12 5
• Long-term PPI users do not routinely need to increase intake of calcium, vitamin B12, or magnesium beyond the Recommended Dietary Allowance 5

Pitfalls and Caveats

• Do not discontinue PPIs solely based on concerns for potential adverse events if there is a clear indication for use 1
• Be aware of the potential for rebound acid hypersecretion when discontinuing PPIs, which may be mistaken for recurrence of the original condition
• Consider that there may be a social gradient in long-term PPI use, with lower income and educational level associated with higher rates of long-term use 6
• Temporary withdrawal of PPIs may be necessary before certain diagnostic tests (e.g., CgA levels for neuroendocrine tumor evaluation) 2

By following this structured approach to managing long-term PPI therapy, clinicians can optimize the benefit-risk ratio for each patient while minimizing unnecessary medication use.