Deprescribing PPI-AGA Practice Update

SUMMARY:

Proton pump inhibitors (PPIs) have been widely used since their advent in the late 1980s, when they first soared in popularity for their ability to treat peptic ulcer disease and as part of the medication regimen for H. pylori infections. In the ensuing years millions of prescriptions for PPIs have been filled, with many patients remaining on these medications chronically with questionable benefit. While generally well tolerated, PPIs do have adverse side effects, and their chronic use increases healthcare costs and the pill burden faced by patients. The American Gastroenterological Association (AGA) has created a guideline to assist primary care providers in deescalating and discontinuing PPIs when no longer indicated.

INDICATIONS AND ADVERSE EFFECTS

Proton pump inhibitors function by irreversibly binding to the hydrogen-potassium ATPase pump located on the luminal side of gastric parietal cells, thus inhibiting gastric acid secretion
Proton pump inhibitors include
- Over the counter: Omeprazole (Prilosec) | Esomeprazole (Nexium) | Lansoprazole (Prevacid)
- Prescription only: Pantoprazole (Protonix) | Rabeprazole (Aciphex) | Dexlansoprazole (Dexilant)
PPIs are indicated for
- GERD
- Zollinger-Ellison Syndrome
- Peptic ulcer disease
- NSAID-associated ulcers
- H. pylori infection
- Eosinophilic esophagitis
- Acute upper GI bleeding
While often used, PPIs are NOT indicated for empiric treatment of laryngopharyngeal symptomatology (e.g., hoarse voice, globus sensation, undifferentiated cough)
Adverse effects and associations include
- Acute kidney injury | Increased risk of chronic kidney disease
- C diff infection | Respiratory infections (e.g., Bacterial pneumonia, COVID-19)
- Neuroendocrine tumors and carcinomas of the gastrointestinal tract
- Malabsorption of minerals and vitamins (e.g., B12, Magnesium, Iron)
- Drug induced lupus
- Dementia

CLINICAL ACTIONS

Primary care providers should regularly review their patient’s medication list, including assessing for chronic PPI use and its indications
- Several PPIs are available over the counter and patients may not report using them unless specifically asked
All patients without a definitive indication for chronic PPI use should trial discontinuation
- Nearly two thirds of PPI users have no clear indication for its use
- A history of an adverse event that may have been linked to chronic PPI use is not a reason for discontinuation (I.e., PPIs should be discontinued only when not indicated)
Prior to discontinuation patients should be carefully assessed for risk factors for upper GI bleeding
- Risk factors include: History of upper GI bleed | Taking multiple antithrombotics | NSAID/ASA use | Older age (> 60 years) | Corticosteroid use
Indications for chronic (> 8 weeks) PPI use include
- Complicated GERD (e.g., of severe erosive esophagitis | Esophageal ulcer | Peptic stricture)
- Eosinophilic esophagitis
- Barrett’s esophagus
- Idiopathic pulmonary fibrosis
- Patients at high risk for upper GI bleeding
Additionally, long term PPI use may be indicated for
- Patients with PPI-responsive reflux, dyspepsia, or upper airway symptoms that recur with PPI cessation
- Refractory steatorrhea in chronic pancreatic insufficiency with enzyme replacement
- Secondary prevention of gastric and duodenal peptic ulcers with no concomitant antiplatelet drugs
Patients who discontinue long-term PPI therapy should be advised that they may develop short term upper GI symptoms due to acid hypersecretion
PPI may be discontinued abruptly or with a dose taper (I.e., going from twice a day dosing to once a day dosing before discontinuation)

KEY POINTS:

Primary care providers should regularly review their patient’s PPI use and consider discontinuation for all patients without a clear indication
While PPIs are associated with multiple adverse effects, data presently does not support causation
- PPI discontinuation is based on lack of indication and not due to adverse effects
PPIs may be discontinued abruptly or with a dose taper, and patients should be educated that they may have a period of rebound symptoms after discontinuation