PPIs: Good or Bad? 1. Basics of PPIs. Gastric Acid Basics. Outline. Gastric Acid Basics. Proton Pump Inhibitors (PPI)

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Angelina Howard
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1 Outline Quick basics on Proton Pump Inhibitors (PPIs) PPIs: Good or Bad? What are potential risks of PPI therapy? How to approach your patients American Gastroenterology Association (AGA) recommendations Gastric Acid Basics 1. Basics of PPIs Gastric acid is good Digestion especially protein Absorption nutrients including calcium and iron Gastric acid can be a problem GERD Symptomatic heartburn Erosive Esophagitis/Barrett s Peptic stricture Peptic ulcer disease Dyspepsia GI bleed Gastric outlet obstruction Hypersecretory syndromes Zollinger-Ellison Gastric Acid Basics Treatments before PPI included Antacids H2B blockers: Cimetidine was the first in 1970s Short duration of action Tachyphlaxis Surgical Partial gastrectomy (Bilroth 1 and 2) Vagotomy Pyloroplasty Proton Pump Inhibitors (PPI) Introduction 1988 Omeprazole first on market 2000 Esomeprazole Now novel PPI in development Concentrate in parietal cells bind H/K/ATPase IRREVERSIBLY inhibition up to 36 hrs before acid pumps regenerate High metabolized by CYP 1

healing of erosive esophagitis Dexlansoprazole : Dexilant Dual action PPI (immediate and long acting) in once daily dosing Things that have made the headlines 2.

2 Current PPIs: All are pretty much the same Increased usage Increased problems? Pantoprazole 40mg: Tecta, Pantoloc Rabeprazole 20mg: Pariet Lansoprazole 30mg: Prevacid Omeprazole 20-60mg: Losec Esomeprazole 20-40mg: Nexium (Available OTC) Superior to Omeprazole/Lansoprazole in healing of erosive esophagitis Dexlansoprazole : Dexilant Dual action PPI (immediate and long acting) in once daily dosing Things that have made the headlines 2. What are the potential risks of chronic PPI? Kidney disease: increased CKD, AIN, AKI Dementia Bone fracture MI: decreased Clopidogrel effect due to CYP inhibition Infection: Bacterial overgrowth, Non typhoid Salmonella/Campylobacter, Spontaneous bacterial peritonitis, C Difficile, Community Acquired Pneumonia Micronutrient deficiency: calcium, iron, magnesium, B12 Malignancy: related to increased gastrin What is big challenge in interpreting the headlines (and fake news in general ) What is the quality of the data in terms of risks? Epidemiologic data: large population studies retrospective Residual confounders Randomized data is lacking helps balance confounders as we cannot always correct for them Kidney International (2008) 73,

3 COGENT: Clopidogrel with or without Omeprazole in Coronary Artery Disease COGENT subset: PPI reduces GIB in patients with Dual antiplatelet regardless of ASA dose without change in CV events N Engl J Med Nov 11;363(20): What is the quality of the data in terms of risks? J Am Coll Cardiol Apr 12;67(14): What is the quality of the data of benefit with PPI? Advice 1 Patients with GERD and acid-related complications (i.e., erosive esophagitis or peptic stricture) should take a PPI for short-term healing and for long-term symptom control. 3. AGA Best practice recommendations: What to do with and tell your patients Rationale: PPIs are highly effective in healing esophagitis and for GERD symptom control, and this benefit is likely to outweigh PPI-related risks. There is no evidence for or against PPIs in asymptomatic patients with healed esophagitis or for PPIs beyond 12 months. 3

4 Advice 2 Patients with uncomplicated GERD who respond to short-term PPIs should subsequently attempt to stop or reduce them. Patients who cannot reduce PPIs should consider ambulatory esophageal ph/impedance monitoring before committing to lifelong PPIs to help distinguish GERD from a functional syndrome. The best candidates for this strategy may be patients with predominantly atypical symptoms or those who lack an obvious predisposition to GERD (eg, central obesity, large hiatal hernia). Rationale: Short-term PPIs are highly effective for uncomplicated GERD. Most patients with uncomplicated GERD respond to short-term PPIs and are subsequently able to reduce PPIs to less than daily dosing. Because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation. However, there is no high-quality evidence on which to base this recommendation. Advice 3 Patients with Barrett s esophagus and symptomatic GERD should take a long-term PPI. Rationale: PPIs have a clear symptomatic benefit and a possible benefit in slowing progression of Barrett s. There is likely to be a net benefit for long-term PPIs in these patients. Advice 4 Asymptomatic patients with Barrett s esophagus should consider a long-term PPI. Rationale: The evidence that PPIs slow progression of Barrett s is low in quality but the evidence of PPI adverse effects is also low in quality. Because there is no high quality evidence on either side of this question, this is a weak recommendation and this decision should be individualized with patients. Advice 5 Patients at high risk for ulcer-related bleeding from NSAIDs should take a PPI if they continue to take NSAIDs. Rationale: PPIs are highly effective in preventing ulcer-related bleeding in appropriately selected patients who take NSAIDs, and this benefit is likely to outweigh PPI-related risks. Advice 6 The dose of long-term PPIs should be periodically reevaluated so that the lowest effective PPI dose can be prescribed to manage the condition. Rationale: Long-term PPI users often receive PPIs at doses higher than necessary to manage their condition. Since PPI reduction is often successful, it is logical to periodically reevaluate PPI dosing so that the minimum necessary dose is prescribed. Advice 7 Long-term PPI users should not routinely use probiotics to prevent infection. Rationale: There is no evidence for or against probiotics to prevent infections in long-term users of PPIs. 4

5 Advice 8 Long-term PPI users should not routinely raise their intake of calcium, vitamin B12 or magnesium beyond the Recommended Dietary Allowance (RDA). Rationale: There is no evidence for or against use of vitamins or supplements beyond the RDA in long-term users of PPIs. Many adults fall below the RDA in several vitamins or minerals and, in these adults, it is reasonable to raise intake to meet the RDA regardless of PPI use. Advice 9 Long-term PPI users should not routinely screen or monitor bone mineral density, serum creatinine, magnesium, or vitamin B12. Rationale: There is no evidence for or against dedicated testing for patients taking long-term PPIs. Such screening (eg, for iron or vitamin B12 deficiency) can be offered but is of no proven benefit. Advice 10 Specific PPI formulations should not be selected based on potential risks. Rationale: There is no convincing evidence to rank PPI formulations by risk. Who to refer for evaluation? Barrett s screening Chronic GERD > 5 years and 2 of: Age > 50 Male Tobacco usage Central obesity Caucasian Dysphagia Refractory GERD You can consider ordering 24 hr ph with impedance +/- manometry Check Celiac serology and trial Lactose free Functional GERD similar to IBS Am J Gastroenterol Jan;111(1):30-50; What to tell your patient Pearls GERD Complicated (Esophagitis, Stricture) Uncomplicated Short term PPI Identify the indication Strengthens argument for or against long term usage Reassurance and monitoring Barretts GERD no GERD Consider PPI Reassess dosing and duration Trials of discontinuation Rebound reflux: taper off NSAIDS Long term Short term No PPI Assess indications for endoscopy ASA Plavix Monotherapy PPI No PPI (unless history of PUD, GIB or GERD) Continue to assess lowest dose and duration 5

Appropriate Use of Proton Pump Inhibitors (PPIs) Anderson Mabour, Pharm.D., BCPS Clinical Pharmacy Specialist

Appropriate Use of Proton Pump Inhibitors (PPIs) Anderson Mabour, Pharm.D., BCPS Clinical Pharmacy Specialist Disclosures I have no actual or potential conflicts of interest to report in relation to this