Management of Chronic Proton Pump Inhibitor Therapy
All patients on chronic PPI therapy must have their indication documented and regularly reviewed by their primary care provider, with those lacking a definitive ongoing indication considered for de-prescribing. 1
Initial Assessment: Document the Indication
Every patient on chronic PPI therapy requires clear documentation of why they are taking the medication 1. The primary care provider should be responsible for this ongoing review 1.
Definitive Indications for Long-Term PPI Use
Patients with the following conditions should continue chronic PPI therapy 1:
- Barrett's esophagus (even if asymptomatic) 1, 2
- Severe erosive esophagitis (Los Angeles grade C/D), esophageal ulcer, or peptic stricture 1, 3
- Eosinophilic esophagitis (requires omeprazole 20 mg twice daily specifically) 1
- High risk for upper GI bleeding while on NSAIDs/anticoagulants/antiplatelets 1
- Idiopathic pulmonary fibrosis 1
Candidates for De-Prescribing
Patients without a definitive indication should be considered for trial of de-prescribing 1. This includes:
- Non-erosive reflux disease with no sustained response to high-dose PPI 1
- Empiric treatment without confirmed GERD 1
- Completed short-term treatment courses (H. pylori eradication, healed peptic ulcer) 1
Dose Optimization for Continued Users
Step-Down from Twice-Daily Dosing
Most patients on twice-daily PPI should be stepped down to once-daily dosing 1. Twice-daily dosing is not FDA-approved for most indications, increases costs, and has been associated with higher rates of adverse events including pneumonia, hip fracture, and C. difficile infection 1, 3. The exception is eosinophilic esophagitis, which requires omeprazole 20 mg twice daily 1.
Titration to Lowest Effective Dose
For patients with proven GERD requiring chronic therapy, titrate to the lowest effective dose that controls symptoms 1, 2. After 4-8 weeks of initial therapy, assess response and wean down if symptoms remain controlled 1. Some patients may be able to transition to on-demand therapy, but this is not appropriate for those with documented erosive esophagitis 3.
Confirming Need for Lifelong Therapy
Reflux Testing at One Year
Patients on chronic PPI for typical reflux symptoms should undergo reflux testing at the 1-year mark to determine appropriateness of lifelong therapy 1. Testing should be performed off PPI for multiple days 1:
- No GERD: AET <4.0% on all days of prolonged wireless pH monitoring with normal endoscopy—stop PPI 1
- Conclusive GERD: Los Angeles grade B or higher esophagitis and/or AET ≥6.0% on 2+ days—continue PPI 1
- Borderline GERD: LA grade A esophagitis and/or AET ≥4.0% but not meeting conclusive criteria—optimize PPI, aggressive lifestyle modifications, consider behavioral therapy 1
De-Prescribing Strategy
Patient Counseling About Rebound Symptoms
Warn all patients that they may develop transient upper GI symptoms due to rebound acid hypersecretion (RAHS) after stopping long-term PPI 1. This physiologic phenomenon can last up to 8 weeks and does not indicate need for continued therapy 1.
Method of Discontinuation
Either dose tapering or abrupt discontinuation can be used 1. There is no strong evidence favoring one approach over the other 1.
Common Pitfalls to Avoid
Do not discontinue PPIs based solely on concern for adverse events 1. The decision should be based only on lack of indication, not fear of potential complications like kidney disease, fractures, or dementia—these associations are observational and not proven causal 2, 4
Do not use on-demand or intermittent therapy for documented erosive esophagitis 3. This approach results in high recurrence rates and is only appropriate for non-erosive reflux disease 3
Do not prescribe twice-daily dosing as initial therapy 3. It is not FDA-approved for erosive esophagitis and lacks evidence support 3
Do not de-prescribe in high-risk GI bleeding patients 1. This includes those with history of upper GI bleeding, taking multiple antithrombotics, or taking aspirin/NSAIDs with additional risk factors (age >60, severe comorbidity, concurrent anticoagulant/corticosteroid use) 1
Monitoring During Long-Term Use
Do not routinely screen or monitor bone mineral density, serum creatinine, magnesium, vitamin B12, or calcium levels in long-term PPI users 2. Do not routinely prescribe probiotics or increase intake of calcium, vitamin B12, or magnesium beyond the Recommended Dietary Allowance 2.
However, be aware of FDA warnings regarding acute tubulointerstitial nephritis (can occur at any point), C. difficile-associated diarrhea (especially in hospitalized patients), bone fractures (with high-dose, long-term use), and cutaneous/systemic lupus erythematosus 5, 6.
Drug Interactions Requiring Action
- Avoid omeprazole with clopidogrel (reduces antiplatelet effect even when dosed 12 hours apart)—consider alternative antiplatelet therapy 5
- Contraindicated with rilpivirine-containing products 5
- Monitor INR closely with warfarin (increased bleeding risk) 5
- Consider temporary withdrawal with high-dose methotrexate (risk of methotrexate toxicity) 5