proton pump inhibitor
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Indications
- peptic ulcer[5]; more effective than H2 blockers
- short-term treatment of severe erosive esophagitis
- short-term treatment of gastroesophageal reflux disease
- patients who respond should attempt to reduce dose or discontinue PPI[59]
- indications for long-term use of PPI[72]
- pathologic hypersecretory conditions
- long-term antiplatelet therapy if:[7]
- history of peptic ulcer
- history of gastrointestinal bleeding
- dual antiplatelet therapy or concomitant anticoagulation
- additional risk factors (age >= 60, steroid use, dyspepsia, or gastroesophageal reflux)
- Barrett's esophagus & symptomatic GERD[59]
- eosinophilic esophagitis
- peptic stricture
- possibly idiopathic pulmonary fibrosis
- component of combination therapy for Helicobacter pylori
Contraindications
- probably not indicated for routine treatment of asthma[9]
- not effective for unexplained throat symptoms (pain, hoarseness, excessive mucus, globus sensation)[70]
- probably overprescribed[14]
- not effective in infants[16]; may be effective in children & adolescents
- not effective in prevention of GI bleeding due to warfarin[39]
- discontinue if indication has resolved[19]
Benefit/risk
- proton pump inhibitor of no benefit for acute peptic ulcer bleeding or other cause of acute upper GI bleed before[24] or after endoscopy[25]
- post-endoscopy acute peptic ulcer bleeding
- number needed to treat (NNT)
- no benefit for reducing
- mortality
- neeed for blood transfusion
- need for repeat endoscopy
- need for surgery
- length of hospital stay[25]
- 15 to prevent rebleeding
- no benefit for reducing
- no harm noted[25]
- number needed to treat (NNT)
- number needed to harm
- 286 for 1 year to cause 1 case of chronic renal failure
Dosage
- administer in AM, 20-45 minutes before 1st meal
- efficacy of PPI maximum when taken before meals[63]
- pantoprazole (Protonix) available for IV injection
- omeprazole may be available for IV injection
- intravenous & oral administration equally effective[18][31] even for bleeding peptic ulcer[44]
- very high high doses (> 60 mg omeprazole) do not provide better acid suppression than lower doses[52]
- TID dosing has no benefit over BID dosing[52]
- BID dosing has no benefit over QD dosing[19]
- generic forms of PPIs most cost-effective[52]
- use lowest effective dose[59]
- for patients without esophagitis, attempt to discontinue or reduce dose of PPI after 1 year[19]* *
* see deprescribing proton-pump inhibitors
Pharmacokinetics
- bioavailability 35-90%
- highly protein bound (90-97%)
- rapidly metabolized in the liver (cyt P450)
- elimination 1/2life of 1-1.5 hours
- duration of acid inhibition: 48-72 hours
Monitor
- 24 hour esophageal pH monitoring not routinely indicated[19]
- pharmacy guidelines require reassessmen5 or need after 8 weeks
Adverse effects
- most common
- headache, diarrhea, abdominal pain (dyspepsia), constipation
- switching to another PPI is generally sufficient to reduce or eliminate the adverse effect(s)[19]
- increased risk of C difficile colitis[4][17][45]
- increased risk for pneumonia
- increased risk of community-acquired pneumonia
- increased risk likely due to confounding factors[41]
- increased risk of nosocomial pneumonia (HR=2.5)[11][12]
- increased risk of nosocomial pneumonia in stroke patients[22]
- no data shows stopping PPI reduces risk of pneumonia[35]
- increased risk of community-acquired pneumonia
- increased risk of serious infection, including severe or fatal COVID-19 (RR=1.46)[69], hepatic encephalopathy & bacterial peritonitis in cirrhotic patients with ascites[10][40]
- H2 receptor antagonists apparently safe[10]
- increased risk for multidrug-resistant organisms[68]
- rebound gastric hyperacidity may occur in patients when proton pump inhibitor is stopped after 2 months of use; best managed with antiacids[13]
- increased risk of acute interstitial nephritis[19][21][32] (hypersensitivity)
- increased risk for chronic renal failure (14.2 vs 10.7 per 1000 person-years, RR=1.3, NNH=286 for 1 year)[29]
- RR=1.3 for 2-fold increase in serum creatinine or 30% decrease in eGFR[47]
- 0.5% excess absolute risk for >50% reduction in GFR within 5 years[49]
- 2-fold increase in cardiovascular mortality with PPI use
- increased risk in MI (RR=1.16)[27]
- no increased risk in MI[54]
- H2-blockers not associated with increased risk
- increased risk of stroke within 180 days of initiation of PPI therapy (RR=1.28, RR=1.77 within 30 days)[46]
- not associated with increased risk for stroke[55]
- increase risk of all-cause mortality relative to use of H2-blockers or no acid suppression (RR=1.25)[48]
- excess mortality from CV disease & chronic kidney disease[65]
- increased risk of dementia in the elderly (RR=1.44)[30]
- increased risk for dementia (RR=1.85)[75]
- longer use of PPI associated with increased risk of dementia[76]
- no increased risk for Alzheimer's disease[50]
- PPI use associated with diminished risk of cognitive impairment[51]
- no increased risk of dementia[56][67]
- increased risk for dementia (RR=1.85)[75]
- hypomagnesemia[19]
- increased risk of fundic gland polyps (RR=2.46)[38]
- increased risk of gastric cancer
- 2-fold independent of prior H pylori infection[53]
- RR=1.45, number needed to harm 2100 in 5 years[71]
- not associated with changes in bone mineral density[42]
- association with risk of hip fracture inconsistent[19]
- no increased risk of hip fracture[57]
- fracture risk increased at higher PPI doses & for duration of therapy > 1 year[19]
- association with risk of hip fracture inconsistent[19]
- increased risk for iron deficiency anemia (RR=2.5)[43]
- vitamin B12 deficiency[19]
- use during the 1st 6 months of life associated with increased risk for food allergy during childhood (RR=2.6)[58]
- long-term use of PPIs is associated with increased risk of type 2 diabetes[74]
- long-term use of PPIs is associated with increased risk of NAFLD non-alcoholic fatty liver disease (RR=2.0 for use > 5 years)[73]
- 5-12 years of continuous PPI therapy presents no major safety concerns[26]
Drug interactions
- proton pump inhibitors may inhibit absorption of levothyroxine in tablet form[23]
- switching to oral solution corrects impaired absorption
- no increase in risk for adverse cardiovascular events with addition of a PPI to clopidogrel[28]
- drug interaction(s) of levothyroxine with proton pump inhibitors
- drug interaction(s) of palbociclib with proton pump inhibitors
- drug interaction(s) of methotrexate with proton pump inhibitors
- drug interaction(s) of bisphosphonates with proton pump inhibitors
- drug interaction(s) of aspirin with proton pump inhibitors
- drug interaction(s) of antiplatelet agents with proton pump inhibitors
- drug interaction(s) of clopidogrel with proton pump inhibitors
- drug interaction(s) of ginko biloba with proton pump inhibitors
Laboratory
- elevated serum gastrin[71]
Mechanism of action
- covalent binding to cysteine residues of the H+/K+ ATPase (proton pump)
- inhibition of the proton pump & gastric acid secretion
- esomeprazole (active stereoisomer of omeprazole) may be most effective PPI[3]
- no convincing evidence that any PPI more effective than another for any indication[34]
- more effecting than H2 blockers to peptic ulcer bleeding[5]
- PPIs don't provide continuous acid suppression... even with BID dosing - nighttime acid breakthrough occurs in > 70% of patients
- acid secretion triggered by histamine may not be effectively inhibited by proton pump inhibitors[6]
More general terms
More specific terms
- dexlansoprazole (Kapidex, Dexilant)
- lansoprazole (Prevacid)
- omeprazole (Prilosec, Zegerid, Losec, Medral)
- pantoprazole (Protonix)
- rabeprazole (Aciphex)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Barkun A et al, Ann Intern Med 139:843, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14623622
- ↑ 3.0 3.1 Journal Watch 24(2):19, 2004 Miner P et al, Am J Gastroenterol 98:2616, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14687806
- ↑ 4.0 4.1 Prescriber's Letter 11(8): 2004 Proton Pump Inhibitors Associated with Increased Risk of Clostridium difficile Diarrhea Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200804&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 5.0 5.1 5.2 Journal Watch 25(10):80, 2005 Leontiadis GI, Sharma VK, Howden CW. Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ. 2005 Mar 12;330(7491):568. Epub 2005 Jan 31. Review. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15684023 <Internet> http://bmj.bmjjournals.com/cgi/content/full/330/7491/568
- ↑ 6.0 6.1 Prescriber's Letter 14(3): 2007 What You Should Know About Proton Pump Inhibitors Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230307&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 Prescriber's Letter 16(3): 2009 Comparison of Proton Pump Inhibitors Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250304&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Bhatt DL et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use. Am J Gastroenterol 2008 Nov; 103:2890.
Bhatt DL et al, ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008 Oct 28;52(18):1502-17. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19017521
Bhatt DL et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation 2008 Oct 28; 118:1894. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18836135 - ↑ 9.0 9.1 Prescriber's Letter 16(6): 2009 Do Proton Pump Inhibitors (PPIs) Improve Asthma? Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250609&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 10.2 Bajaj JS et al Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol 2009 May; 104:1130. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19337238
Bajaj JS et al. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Aliment Pharmacol Ther 2012 Sep 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22966967 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/apt.12045/abstract;jsessionid=63AAEC22827345E993522335B4680B03.d02t03 - ↑ 11.0 11.1 Herzig SJ et al, Acid-Suppressive Medication Use and the Risk for Hospital- Acquired Pneumonia JAMA. 2009;301(20):2120-2128 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19470989
- ↑ 12.0 12.1 Prescriber's Letter 16(7): 2009 Overuse of Acid Suppressing Drugs in the Hospital Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250720&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 13.0 13.1 Reimer C et al. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009 Jul; 137:80. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19362552
McColl KEL and Gillen D. Evidence that proton-pump inhibitor therapy induces the symptoms it is used to treat. Gastroenterology 2009 Jul; 137:20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19482105 - ↑ 14.0 14.1 Yachimski PS et al Proton Pump Inhibitors for Prophylaxis of Nosocomial Upper Gastrointestinal Tract Bleeding Arch Intern Med. 2010;170(9):779-783. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458085 <Internet> http://archinte.ama-assn.org/cgi/content/short/170/9/779
Katz MH Failing the Acid Test: Benefits of Proton Pump Inhibitors May Not Justify the Risks for Many Users Arch Intern Med. 2010;170(9):747-748. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458079 <Internet> http://archinte.ama-assn.org/cgi/content/short/170/9/747 - ↑ Prescriber's Letter 17(7): 2010 COMMENTARY: Proton Pump Inhibitors: Appropriate Use and Safety Concerns CHART: Comparison of Proton Pump Inhibitors PATIENT HANDOUT: What You Should Know About Proton Pump Inhibitors Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260705&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 16.0 16.1 van der Pol RJ et al. Efficacy of proton-pump inhibitors in children with gastroesophageal reflux disease: A systematic review. Pediatrics 2011 May; 127:925. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21464183
- ↑ 17.0 17.1 FDA MedWatch: 02/08/2012 Proton Pump Inhibitors (PPIs) - Drug Safety Communication: Clostridium Difficile-Associated Diarrhea (CDAD) Can be Associated With Stomach Acid Drugs http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm290838.htm
- ↑ 18.0 18.1 Tsoi KKF et al. Meta-analysis: Comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther 2013 Aug 5 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23915096 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/apt.12441/abstract;jsessionid=E794CBFDD7F82B48FD8A6988F29BE49B.d04t04
- ↑ 19.00 19.01 19.02 19.03 19.04 19.05 19.06 19.07 19.08 19.09 19.10 Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18, 19. American College of Physicians, Philadelphia 2012. 2015, 2018, 2021.
- ↑ Heidelbaugh JJ. PPI therapy: when to worry about fracture risk. J Fam Pract. 2011 May;60(5):255-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21544271
- ↑ 21.0 21.1 Blank ML et al A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int 2014 Oct; 86:837 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24646856
Muriithi AK et al. Biopsy-proven acute interstitial nephritis, 1993 - 2011: A case series. Am J Kidney Dis 2014 Oct; 64:558 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24927897 - ↑ 22.0 22.1 Herzig SJ et al. Acid-suppressive medication use in acute stroke and hospital- acquired pneumonia. Ann Neurol 2014 Nov; 76:712 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25164323
- ↑ 23.0 23.1 Vita R et al. Switching levothyroxine from the tablet to the oral solution formulation corrects the impaired absorption of levothyroxine induced by proton-pump inhibitors. J Clin Endocrinol Metab 2014 Dec; 99:4481 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25259910 <Internet> http://press.endocrine.org/doi/abs/10.1210/jc.2014-2684
- ↑ 24.0 24.1 The NNT: Proton Pump Inhibitors (PPIs) Given for Acute Upper Gastrointestinal Bleeding Given Prior to Endoscopic Diagnosis. http://www.thennt.com/nnt/proton-pump-inhibitors-for-acute-upper-gi-bleeding/
Sreedharan A, Martin J, Leontiadis GI et al Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010 Jul 7;(7):CD005415 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20614440 - ↑ 25.0 25.1 25.2 25.3 The NNT: Proton Pump Inhibitors (PPIs) Given for Acute Peptic Ulcer Bleeding http://www.thennt.com/nnt/proton-pump-inhibitors-for-acute-peptic-ulcer-bleeding/
Leontiadis GI, McIntyre L, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database Syst Rev. 2004;(3):CD002094 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15266462 - ↑ 26.0 26.1 Attwood SE et al. Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: Data from the SOPRAN and LOTUS studies. Aliment Pharmacol Ther 2015 Apr 10; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25858519 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/apt.13194/abstract
- ↑ 27.0 27.1 Shah NH, LePendu P, Bauer-Mehren A et al Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLOS One. Published: June 10, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26061035 <Internet> http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124653
- ↑ 28.0 28.1 Cardoso RN et al. Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: An updated meta-analysis. Open Heart 2015; 2:e000248 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26196021 <Internet> http://openheart.bmj.com/content/2/1/e000248
- ↑ 29.0 29.1 Lazarus B, Chen Y, Wilson FP et al Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. Published online January 11, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26752337 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2481157
Schoenfeld AJ, Grady D Adverse Effects Associated With Proton Pump Inhibitors. JAMA Intern Med. Published online January 11, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26751904 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2481153 - ↑ 30.0 30.1 Gomm W, von Holt K, Thome F et al Association of Proton Pump Inhibitors With Risk of Dementia. A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. Published online February 15, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26882076 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2487379
Kuller LH Do Proton Pump Inhibitors Increase the Risk of Dementia? JAMA Neurol. Published online February 15, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26882528 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2487375 - ↑ 31.0 31.1 Jian Z et al. Is the era of intravenous proton pump inhibitors coming to an end in patients with bleeding peptic ulcers? Meta-analysis of the published literature. Br J Clin Pharmacol 2015 Dec 18 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26679691
- ↑ 32.0 32.1 Chang YS. Hypersensitivity reactions to proton pump inhibitors. Curr Opin Allergy Clin Immunol. 2012 Aug;12(4):348-53. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22744268
- ↑ Brewster UC, Perazella MA. Proton pump inhibitors and the kidney: critical review. Clin Nephrol. 2007 Aug;68(2):65-72. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17722704
- ↑ 34.0 34.1 Therapeutics Letter > [99] June 28, 2016 Comparative effectiveness of proton pump inhibitors. http://www.ti.ubc.ca/2016/06/28/99-comparative-effectiveness-proton-pump-inhibitors/
- ↑ 35.0 35.1 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
- ↑ Abrahamsen B, Vestergaard P. Proton pump inhibitor use and fracture risk - effect modification by histamine H1 receptor blockade. Observational case-control study using National Prescription Data. Bone. 2013 Nov;57(1):269-71. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23973557
- ↑ Reimer C. Safety of long-term PPI therapy. Best Pract Res Clin Gastroenterol. 2013 Jun;27(3):443-54. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23998981
- ↑ 38.0 38.1 Martin FC et al. Systematic review with meta-analysis: Fundic gland polyps and proton pump inhibitors. Aliment Pharmacol Ther 2016 Sep 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27634363
- ↑ 39.0 39.1 Ray WA, Chung CP, Murray KT et al. Association of proton pump inhibitors with reduced risk of warfarin-related serious upper gastrointestinal bleeding. Gastroenterology 2016 Sep 14 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27639805
- ↑ 40.0 40.1 Dam G, Vilstrup H, Watson H, Jepsen P. Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology. 2016 Oct;64(4):1265-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27474889
- ↑ 41.0 41.1 Othman F, Crooks CJ, Card TR Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study. BMJ 2016;355:i5813 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28715344 Free PMC Article <Internet> http://www.bmj.com/content/355/bmj.i5813
Filion KB, Chateau D, Targownik LE et al, CNODES Investigators.. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut. 2014 Apr;63(4):552-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23856153 Free PMC Article - ↑ 42.0 42.1 Targownik LE et al. Long-term proton pump inhibitor use is not associated with changes in bone strength and structure. Am J Gastroenterol 2016 Nov 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27845341
- ↑ 43.0 43.1 Lam JR et al. Proton pump inhibitor and histamine-2 receptor antagonist use and iron deficiency. Gastroenterology 2016 Nov 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27890768
- ↑ 44.0 44.1 Tringali A, Manta R, Sica M et al. Comparing intravenous and oral proton pump inhibitor therapy for bleeding peptic ulcers following endoscopic management. A systematic review and meta-analysis. Br J Clin Pharmacol 2017 Feb 9 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28181291 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/bcp.13258/abstract
- ↑ 45.0 45.1 Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of gastric acid suppression with recurrent Clostridium difficile infection: A systematic review and meta-analysis. JAMA Intern Med 2017 Mar 27 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28346595
- ↑ 46.0 46.1 Wang YF, Chen YT, Luo JC, Chen TJ, Wu JC, Wang SJ. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: A nationwide population- based study. Am J Gastroenterol 2017 Apr 11; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28397874
- ↑ 47.0 47.1 Klatte DCF, Gasparini A, Xu H et al. Association between proton pump inhibitor use and risk of progression of chronic kidney disease. Gastroenterology 2017 Jun 2 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28583827
- ↑ 48.0 48.1 Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017 Jul 4;7(6):e015735. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28676480 Free Article <Internet> http://bmjopen.bmj.com/content/7/6/e015735
- ↑ 49.0 49.1 Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int 2017 Jun; 91:1482. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28237709 Free Article
- ↑ 50.0 50.1 Taipale H, Tolppanen AM, Tiihonen M et al. No association between proton pump inhibitor use and risk of Alzheimer's disease. Am J Gastroenterol 2017 Jul 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28695906
Lochhead P, Hagan K, Joshi AD et al. Association between proton pump inhibitor use and cognitive function in women. Gastroenterology 2017 Jul 17; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28728964 - ↑ 51.0 51.1 Goldstein FC, Steenland K, Zhao L et al Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc 2017 Sep; 65:1969-1974 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28590010
- ↑ 52.0 52.1 52.2 52.3 Graham DY, Tansel A. Interchageable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol. 2017 Sep 28. pii: S1542-3565(17)31168-0 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28964908
- ↑ 53.0 53.1 Brooks M Gastric Cancer Risk Doubled With Long-term PPI Use. Medscape. Oct 31, 2017. https://www.medscape.com/viewarticle/887863
Cheung KS, Chan EW, Wong AYS et al Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. Nov 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29089382 <Internet> http://gut.bmj.com/content/early/2017/09/18/gutjnl-2017-314605 - ↑ 54.0 54.1 Landi SN, Sandler RS, Pate V, Lund JL. No increase in risk of acute myocardial infarction in privately insured adults prescribed proton pump inhibitors vs histamine-2 receptor antagonists (2002-2014). Gastroenterology 2017 Nov 6; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29122546 <Internet> http://www.gastrojournal.org/article/S0016-5085(17)36330-8/pdf
- ↑ 55.0 55.1 Nguyen LH, Lochhead P, Joshi AD et al. No significant association between proton pump inhibitor use and risk of stroke after adjustment for lifestyle factors and indication. Gastroenterology 2017 Dec 18 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29269313 <Internet> http://www.gastrojournal.org/article/S0016-5085(17)36710-0/pdf
- ↑ 56.0 56.1 Gray SL, Walker RL, Dublin S et al. Proton pump inhibitor use and dementia risk: Prospective population-based study. J Am Geriatr Soc 2018 Feb; 66:247. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29134629
- ↑ 57.0 57.1 Torvinen-Kiiskinen S, Tolppanen AM, Koponen M et al. Proton pump inhibitor use and risk of hip fractures among community-dwelling persons with Alzheimer's disease - A nested case-control study. Aliment Pharmacol Ther 2018 Apr; 47:1135; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29508411
- ↑ 58.0 58.1 Mitre E, Susi A, Kropp LE, et al Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood. JAMA Pediatr. Published online April 2, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29610864 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2676167
- ↑ 59.0 59.1 59.2 59.3 Freedberg DE, Kim LS, Yang Y. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017 Mar;152(4):706-715. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28257716
- ↑ Clooney AG, Bernstein CN, Leslie WD et al A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors. Aliment Pharmacol Ther. 2016 May;43(9):974-84. Epub 2016 Feb 29. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26923470 Free Article
- ↑ Lewis PO, Lundberg TS, Tharp JL, Runnels CW. Implementation of Global Strategies to Prevent Hospital-Onset Clostridium difficile Infection: Targeting Proton Pump Inhibitors and Probiotics. Ann Pharmacother. 2017 Oct;51(10):848-854. Epub 2017 Aug 18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28821215
- ↑ Farrell B, Pottie K, Thompson W et al Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician. 2017 May;63(5):354-364. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28500192 Free PMC Article
- ↑ 63.0 63.1 NEJM Knowledge+. Question of the Week. July 24, 2018 https://knowledgeplus.nejm.org/question-of-week/1678/
- ↑ Moledina DG, Perazella MA. PPIs and kidney disease: from AIN to CKD. J Nephrol. 2016 Oct;29(5):611-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27072818
- ↑ 65.0 65.1 Xie Y, Bowe B, Yan Y Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. BMJ 2019;365:l1580 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31147311 https://www.bmj.com/content/365/bmj.l1580
- ↑ Moayyedi P, Eikelboom JW, Bosch J et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019 Sept. 157(3):682-691. epub May 29. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31152740 https://www.gastrojournal.org/article/S0016-5085(19)40974-8/fulltext
Moayyedi P, Eikelboom JW, Bosch J et al. Pantoprazole to prevent gastroduodenal events in patients receiving rivaroxaban and/or aspirin in a randomized, double-blind, placebo-controlled trial. Gastroenterology 2019 Aug; 157:403 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31054846 https://www.gastrojournal.org/article/S0016-5085(19)36764-2/fulltext - ↑ 67.0 67.1 Khan MA, Yuan Y, Iqbal U et al. No association linking short-term proton pump inhibitor use to dementia: Systematic review and meta-analysis of observational studies. Am J Gastroenterol 2020 Jan 2. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31895707 https://journals.lww.com/ajg/Abstract/publishahead/No_Association_Linking_Short_Term_Proton_Pump.99461.aspx
- ↑ 68.0 68.1 Willems RPJ, van Dijk K, Ket JCF et al. Evaluation of the association between gastric acid suppression and risk of intestinal colonization with multidrug-resistant microorganisms: A systematic review and meta-analysis. JAMA Intern Med 2020 Feb 24; PMID 32091544 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2761273
Lee TC, McDonald EG. Deprescribing proton pump inhibitors: Overcoming resistance. JAMA Intern Med 2020 Feb 24; PMID: https://www.ncbi.nlm.nih.gov/pubmed/32091554 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2761268 - ↑ 69.0 69.1 Brooks M PPI Use Tied to Increased Risk of Severe or Fatal COVID-19 Outcome in Meta-Analysis. Medscape - Nov 04, 2020. https://www.medscape.com/viewarticle/940390
- ↑ 70.0 70.1 O'Hara J, Stocken DD, Watson GC et al Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial. BMJ 2021;372:m4903 Jan 7, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33414239 Free article https://www.bmj.com/content/372/bmj.m4903
- ↑ 71.0 71.1 71.2 Abrahami D et al. Proton pump inhibitors and risk of gastric cancer: Population-based cohort study. Gut 2022 Jan; 71:16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34226290 https://gut.bmj.com/content/71/1/16
- ↑ 72.0 72.1 Targownik LE et al. AGA clinical practice update on de-prescribing of proton pump inhibitors: Expert review. Gastroenterology 2022 Apr; 162:1334. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35183361 https://www.gastrojournal.org/article/S0016-5085(21)04083-X/fulltext
- ↑ 73.0 73.1 Huang H et al Long-term Use of Proton Pump Inhibitors is Associated With An Increased Risk of Nonalcoholic Fatty Liver Disease. J Clin Gastroenterol. 2023. March 31 Not indexed in PubMed https://journals.lww.com/jcge/Abstract/9900/Long_term_Use_of_Proton_Pump_Inhibitors_is.144.aspx
- ↑ 74.0 74.1 Loosen SH et al. Long-term use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes. Gut. 2022. Aug;71(8):1687-1688 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34725199
- ↑ 75.0 75.1 Ahn N, Wawro N, Baumeister SE et al Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany. Drug & Aging. 2023. May 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37178361 https://link.springer.com/article/10.1007/s40266-023-01031-7
- ↑ 76.0 76.1 George J Dementia Risk Linked With Cumulative Heartburn Med Use, Analysis Suggests. Study adds to the ongoing discussion about proton pump inhibitors and cognition. MedPage Today August 9, 2023 https://www.medpagetoday.com/neurology/dementia/105827
Northuis C, Bell E, Lutsey P et al Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. Neurology, 2023. August 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37558503 https://n.neurology.org/content/early/2023/08/09/WNL.0000000000207747
Ahn N, Wawro N, Baumeister SE et al Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany. Drug & Aging. 2023. May 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37178361 https://link.springer.com/article/10.1007/s40266-023-01031-7