Z Gastroenterol 2018; 56(03): 264-274
DOI: 10.1055/s-0043-125340
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Verordnungspraxis und Risiken von Protonenpumpenblockern – Fiktion und Fakten

Prescription and risks of proton pump inhibitor: fiction and facts
Herbert Koop
ehemals Klinik für Allgemeine Innere Medizin und Gastroenterologie, Helios Klinikum Berlin-Buch
› Author Affiliations
Further Information

Publication History

30 August 2017

21 December 2017

Publication Date:
16 January 2018 (online)

Zusammenfassung

Derzeit werden ein nicht-indikationsgerechter Einsatz und potenzielle Risiken einer Therapie mit Protonenpumpeninhibitoren (PPI) intensiv diskutiert. Diese Übersichtsarbeit beleuchtet kritisch das Verschreibungsverhalten bzgl. PPI in Praxis und Klinik, zeigt Exit-Strategien aus einer langfristigen PPI-Behandlung auf und evaluiert kritisch das Risikoprofil von PPI.

Abstract

There is substantial discussion about inappropriate prescriptions and risks of proton pump inhibitor (PPI) therapy. This review critically reviews prescription manners regarding PPI both by general practitioners and in hospitals, demonstrates exit strategies after prolonged PPI treatment and evaluates clinically relevant risks of PPI therapy.

 
  • Literatur

  • 1 Mössner J. Indikationen, Nutzen und Risiken von Protonenpumpeninhibitoren. Eine Bestandsaufnahme nach 25 Jahren. Dtsch Aerztebl Intern 2016; 113: 477-483
  • 2 https://www.dgvs.de/wp-content/uploads/2017/01/PM_2017_01_Protonenpumpeninhibitoren.pdf (eingesehen am 17.08.2017)
  • 3 Scarpignato C, Gatta L, Zullo A. et al. Effective and safe proton pump inhibitor therapy in acid related diseases – a position paper addressing the benefits and potential harms of acid suppression. BMC Medicine 2016; 14: 179
  • 4 Koop H, Fuchs KH, Labenz J. et al. S2k-Leitlinie: Gastroösophageale Refluxkrankheit unter Federführung der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten. Z Gastroenterol 2014; 52: 1299-1346
  • 5 Labenz J, Koop H. Gastroösophageale Refluxkrankheit: was tun, wenn PPI nicht ausreichend wirksam, verträglich oder erwünscht sind?. Dtsch med Wschr 2017; 142: 356-366
  • 6 Koop H, Labenz J. Ulkuskrankheit – update. Gastroenterol up2date 2016; 12: 193-208
  • 7 Pinto-Sanchez MI, Yuan y, Bercik P. et al. Proton pump inhibitors for functional dyspepsia. Cochrane Database Syst Rev 2017; 3: CD011194
  • 8 Malfertheiner P, Megraud F, O’Morain CA. et al. Management of Helicobacter pylori infection – the Maastricht V / Florence consensus report. Gut 2017; 66: 6-30
  • 9 Dellon ES, Gonsalves N, Hirano I. et al. ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis. Am J Gastroenterol 2013; 108: 679-692
  • 10 McDonald EG, Jones J, Green L. et al. Reduction of inappropriate exit prescriptions of proton pump inhibitors: a before-after study using education paired with a web-based quality-improvement tool. J Hosp Med 2015; 10: 281-286
  • 11 Heidelbaugh JJ, Metz DC, Yang YX. Proton pump inhibitors: are they overutilized in clinical practice and do they pose significant risk?. Intern J Clin Pract 2012; 6: 582-591
  • 12 Jacobsen BC, Ferris TG, Shea TL. et al. Who is using chronic acid suppression therapy and why?. Am J Gastroenterol 2003; 98: 51-58
  • 13 Batuwitage BT, Kingham JGC, Morgan NE. et al. Inappropriate prescribing of proton pump inhibitors in primary care. Postgrad Med J 2007; 83: 66-68
  • 14 Ahrens D, Chenot JF, Behrens G. et al. Appropriateness of treatment recommendations for PPI in hospital discharge letters. Eur J Clin Pharmacol 2010; 66: 1265-1291
  • 15 de Rijdt T, Spriet I, Willems L. et al. Appropriateness of acid suppression therapy. Ann Pharmacother 2017; 51: 125-134
  • 16 Kelly OB, Dillane C, Patchett SE. et al. The inappropriate prescription of oral proton pump inhibitors in the hospital setting: a prospective cross-sectional study. Dig Dis Sci 2015; 60: 2280-2286
  • 17 van Vliet EPM, Otten HJAM, Rudolphus A. et al. Inappropriate prescription of proton pump inhibitors on two pulmonary medicine wards. Eur J Gastroenterol Hepatol 2008; 20: 608-612
  • 18 Lødrup AB, Reimer C, Bytzer P. Systematic review: symptoms of rebound acid hypersecretion following proton pump inhibitor treatment. Sacnd J Gastroenterol 2013; 48: 515-522
  • 19 Krol N, Wending M, Haaijer-Ruskamp F. et al. Patient-directed strategy to reduce prescribing for patients with dyspepsia in general practice: a randomized trial. Aliment Pharmacol Ther 2004; 19: 912-922
  • 20 Björnsson E, Abrahamsson H, Simrén M. et al. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther 2006; 24: 945-954
  • 21 Reimer C, Bytzer P. Discontinuation of long-term proton pump inhibitor therapy in primary care patients: a randomized, placebo-controlled trial in patients with symptom relapse. Eur J Gastroenterol Hepatol 2010; 22: 1182-1188
  • 22 Haastrup P, Paulsen MS, Begtrup LM. et al. Strategies for discontinuation of proton pump inhibitors: a systematic review. Fam Pract 2014; 31: 625-630
  • 23 Grimes DA, Schulz KF. False alarms and pseudo-epidemics. The limitations of observational studies. Obstetr Gynecol 2012; 120: 920-927
  • 24 Othman F, Card TR, Crooks CJ. Proton pump inhibitor prescribing patterns in the U. K.: a primary care database study. Pharmacoepidem Drug Safety 2016; 25: 1079-1087
  • 25 Hvid-Jensen F, Nielsen RB, Pedersen L. et al. Lifestyle factors among proton pump inhibitor users and nonusers: a cross-sectional study in a population-based setting. Clin Epidemiol 2013; 5: 493-499
  • 26 Teramura-Grönblad M, Hosia-Randell H, Muurinen S. et al. Use of proton pump inhibitors and their associated risks among frail elderly nursing home residents. Scand J Prim Health Care 2010; 28: 154-159
  • 27 Lau AN, Tomizza M, Wong-Pack M. et al. The relationship of long-term proton pump inhibitor therapy and skeletal frailty. Endocrine 2015; 49: 606-610
  • 28 Kuschel BM, Laflamme L, Möller J. The risk of fall injury in relation to commonly prescribed medications in older people: a Swedish case-control study. Eur J Public Health 25: 527-532
  • 29 Ngamruengphong S, Leontiadis GI, Radhi S. et al. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol 2011; 106: 1209-1218
  • 30 Cai D, Feng W, Jiang Q. Acid suppressive medications and risk of fracture: an updated meta-analysis. Int J Clin Exp Med 2015; 8: 8893-8904
  • 31 Wright MJ, Sullivan RR, Gaffney-Stromberg E. et al. Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, cross-over, controlled clinical trial. J Bone Min Res 2010; 25: 2205-2211
  • 32 Hansen KE, Jones AN, Lindström MJ. et al. Do proton pump inhibitors decrease calcium absorption?. J Bone Min Res 2010; 25: 2786-2795
  • 33 Solomon DH, Diem SJ, Ruppert K. et al. Bone mineral changes among women initiating proton pump inhibitors or H2 receptor antagonists: a SWAN cohort study. J Bone Min Res 2015; 30: 232-239
  • 34 Targownik LE, Goertzen AL, Luo Y. et al. Long-term proton pump inhibitor use is not associated with bone strength and structure. Am J Gastroenterol 2017; 112: 95-101
  • 35 Frazer LA, Leslie WD, Targownik LE. et al. The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter osteoporosis Study. Osteopor Int 2013; 24: 1161-1168
  • 36 Freedberg DE, Kim LS, Yang YX. 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; 152: 706-715
  • 37 Lambert AA, Lam JO, Paik JJ. et al. Risk of community-acquired pneumonia with outpatient proton pump inhibitor therapy: a systematic review and meta-analysis. PLoS ONE 2015; 10: e0128004
  • 38 Fillon KB, Chateau D, Targownik LE. et al. Proton pump inhibitors and the risk of hospitalsation for community-acquired pneumonia: replicated cohort studies and meta-analysis. Gut 2014; 63: 552-558
  • 39 Estborn L, Joelsen S. Frequency and time of onset of community-acquired respiratory tract infection in patients receiving esomeprazole: a retrospective analysis of patient-level data in placebo-controlled studies. Aliment Pharmacol Ther 2015; 42: 607-613
  • 40 Wijarnpreecha K, Thongprayoon C, Chesdachai S. et al. Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis. Dig Dis Sci 2017; 62: 2821-2827
  • 41 Xie Y, Bowe B, Li T. et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int 2017; 91: 1482-1494
  • 42 Lazarus B, Chen Y, Wilson FP. et al. Proton pump inhibitor use and risk of chronic kidney disease. JAMA Intern Med 2016; 176: 238-246
  • 43 Antoniou T, MacDonald EM, Hollands S. et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open 2015; 3: E166-E171
  • 44 Park CH, Kim EH, Roh YH. et al. The association between the use of proton pump inhibitors and risk of hypomagnesemia: a systematic review and meta-analysis. PLoS ONE 2014; 11: e112558
  • 45 William JH, Danziger J. Magnesium deficiency and proton pump inhibitor use: a clinical review. J Clin Pharmacol 2016; 56: 660-668
  • 46 Atkinson NSS, Reynolds DJM, Travis SPL. ‘Lemonade legs‘: why do some patients get profound hypomagnesemia on proton pump inhibitors?. Intest Res 2015; 13: 227-232
  • 47 Haenisch B, von Holt K, Wiese B. et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci 2015; 265: 419-428
  • 48 Gomm W, von Holt K, Thomé F. et al. Association of proton pump inhibitors and dementia. A pharmacoepidemiological claims data analysis. JAMA Neurol 2016; 73: 410-416
  • 49 Tai SY, Chien CY, Wu DC. et al. Risk of dementia from proton pump inhibitor use in Asian population: a nationwide cohort study in Taiwan. PLoS ONE 2017; 12: e0171006
  • 50 Kuller LH. Do proton pump inhibitors increase the risk of dementia?. JAMA Neurol 2016; 73: 376-378
  • 51 Taipale H, Tolppanen AM, Tiihonen M. et al. No association of proton pump inhibitor use and risk of Alzheimer’s disease. Am J Gastroenterol 2017; 112: 1802-1808
  • 52 Lochhead P, Hagan K, Joshi AD. et al. Association between proton pump inhibitor use and cognitive function in women. Gastroenterology 2017; 153: 971-979
  • 53 Goldstein FC, Steenland K, Zhao L. et al. Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc 2017; 65: 1969-1974
  • 54 Sehested TS, Gerds TA, Frosbøl EL. et al. Long-term use of proton pump inhibitors, dose-response relationship, and associated risk of ischemic stroke and myocardial infarction. J Intern Med 2018; in press, DOI: 10.1111/joim 12698.
  • 55 Wang YF, Chen YT, Luo JC. et al. 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; 112: 1084-1093
  • 56 Ueberschaer H, Allescher HD. Protonenpumpenhemmer – Nebenwirkungen und Komplikationen der langfristigen Protonenpumpenhemmereinnahme. Z Gastroenterol 2017; 55: 63-71
  • 57 Shaw NH, LePendu P, Bauer-Mehren A. et al. Proton pump inhibitor usage and the risk of myocardial infarction in the general population. PLoS ONE 2015; 10: e0124653
  • 58 Jensen BES, Hansen JS, Larsen KS. et al. Randomized clinical trial: the impact of gastrointestinal risk factor screening and prophylactic proton pump inhibitor in patient receiving dual antiplatelet therapy. Eur J Gastroenterol Hepatol 2017; 29: 1118-1125
  • 59 Jackson LR II, Peterson ED, McCoy LA. et al. Impact of Proton Pump Inhibitor Use on the Comparative effectiveness and safety of prasugrel versus clopidogrel: insights from the treatment with adenosine diphosphate receptor inhibitors: longitudinal assessment of treatment patterns and events after acute coronary syndrome (TRANSLATE-ACS) Study. J Am Heart Assoc 2016; 5: e003824
  • 60 Koop H, Bachem J. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol 1992; 14: 288-292
  • 61 Steward CA, Termanini B, Sutliff VE. et al. Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy. Aliment Pharmacol Ther 1998; 12: 83-98
  • 62 Lam JR, Schneider JL, Quesenberry CP. et al. Proton pump inhibitor and histamine-2 receptor antagonist use and iron deficiency. Gastroenterology 2017; 152: 821-829
  • 63 Koop H, Kurz C. Befunde am gastroösophagealen Übergang. Gastroenterol up2date 2007; 3: 33-45
  • 64 Lam JR, Schneider JL, Zhao W. et al. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA 2013; 310: 2435-2442
  • 65 Linder L, Tamboue C, Clements JN. Drug-induced Vitamin B12 deficiency: a focus on proton pump inhibitors and histamine-2 antagonists. J Pharm Pract 2017; 30: 639-642
  • 66 Bavishi C, Du PontHL. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infections. Aliment Pharmacol Ther 2011; 34: 1269-1281
  • 67 Kvistholm JensenA, Simonsen J, Ethelberg S. Use of proton pump inhibitors and the risk of listeriosis: a nationwide registry-based case-control study. Clin Infec Dis 2017; 64: 845-851
  • 68 http://www.rki.de/DE/Content/Infekt/Jahrbuch/Jahrbuch_2016.pdf?blob=publicationFile (eingesehen am 17.8.2017)
  • 69 Brophy S, Jones KH, Rahman MH. et al. Incidents of Campylobacter and Salmonella infections following first prescriptions for PPI: a cohort study using routine data. Am J Gastroenterol 2013; 108: 1094-1100
  • 70 Deshpande A, Pasupuleti V, Thota P. et al. Risk factor for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infect Contr Hosp Epidemiol 2015; 36: 452-460
  • 71 Janarthanan S, Ditah I, Adler DG. et al. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol 2012; 107: 1001-1010
  • 72 Oshima T, Wu L, Li M. et al. Magnitude and direction of the association between Clostridium difficile infection and proton pump inhibitors in adults and pediatric patients: a systematic review and meta-analysis. J Gastroenterol 2018; 53: 84-94
  • 73 Wei L, Ratnayake L, Phillips G. et al. acid-suppression medication and bacterial gastroenteritis: apopulation-based cohort study. Brit J Clin Pharmacol 2017; 83: 1298-1308
  • 74 Lowe DO, Mamdani MM, Kopp A. et al. Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: a population-based study. Clin Infect Dis 2006; 43: 1272-1276
  • 75 Freedberg DE, Lamousé-Smith ES, Lightdale JR. et al. Use of acid suppression medication is associated with risk for C. difficile infection in infants and children: a population-based study. Clin Infect Dis 2015; 61: 912-917
  • 76 Adams DJ, Eberly MD, Rajnik M. et al. Risk factors for community-associated Clostridium difficile infection in children. J Pediatr 2017; 186: 105-109
  • 77 Freedberg DE, Abrams JA. Clostridium difficile infection in the community: are proton pump inhibitors to blame?. W J Gastroenterol 2013; 19: 6710-6713
  • 78 Tsai TS, Hung YP, Lee JC. et al. Community-onset Clostridium difficile infection at a tertiary medical center in southern Taiwan, 2007–2015. J Micobiol Infect Immunol 2016; xx: 1-8
  • 79 Garg S, Mirza YR, Girotra M. et al. Epidemiology of Clostridium difficile-associated disease (CDAD): a shift from hospital-acquired infection to long-term care facility-based infection. Dig Dis Sci 2013; 58: 3407-3412
  • 80 Chitnis AS, Holzbauer SM, Belflower RM. et al. Epidemiology of community-associated Clstridium difficileinfection, 2009 through 2011. JAMA Intern Med 2013; 173: 1359-1367
  • 81 Dam G, Vilstrup H, Watson H. et al. Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology 2016; 64: 1265-1272
  • 82 Tsai CF, Chen MH, Wang YP. et al. Proton pump inhibitors increase risk of hepatic encephalopathy in patients with cirrhosis in a population study. Gastroenterology 2017; 152: 134-141
  • 83 Yu T, Tang Y, Jiang L. et al. Proton pump inhibitor therapy and its association with spontaneous bacterial peritonitis incidence and mortality: a meta-analysis. Dig Liver Dis 2016; 48: 353-359
  • 84 Kim JH, Lim KS, Min YW. et al. Proton pump inhibitors do not increase the risk for recurrent spontaneous bacterial peritonitis in patients with cirrhosis. J Gastroenterol Hepatol 2017; 32: 1064-1070
  • 85 Garcia-Saints-de-Sicilia M, Sanchez-Avila F, Chavez-Tapia NC. et al. PPIs are not associated with a lower incidence of portal-hypertension-related bleeding in cirrhosis. World J Gastroenterol 2010; 16: 5869-5873
  • 86 Eckhardt VF, Grace ND. Gastroesophageal reflux and bleeding esophageal varices. Gastroenterology 1979; 75: 39-42
  • 87 Wee E. Management of nonvariceal upper gastrointestinal bleeding. J Postgrad Med 2011; 57: 161-167
  • 88 Shaheen NJ, Stuart E, Schmitz SM. et al. Pantoprazole reduces the size of postbanding ulcers after variceal band ligation: a randomized controlled trial. Hepatology 2005; 51: 588-594
  • 89 Garg PK, Sidhu SS, Bhargava DK. Role of omeprazole in prevention and treatment of postendoscopic variceal sclerotherapy esophageal complications: double-blind randomized study. Dig Dis Sci 1995; 40: 1569-1574
  • 90 Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology 2017; 153: 35-48
  • 91 Sehested TS, Frosbøl EL, Hansen PW. et al. Proton pump inhibitor use increases the associated risk of first-time ischemic stroke. A nationwide cohort study. Circulation 2016 134. A18462 (abtract)
  • 92 Johnson DA, Katz PO, Armstrong D. et al. The safety of appropriate use of over-the-counter proton pump inhibitors: an evidence-based review and Delphi consensus. Drugs 2017; 77: 547-561
  • 93 Jung N, Koop H, Riessen R. et al. „Klug entscheiden“ bei Infektionskrankheiten – zu häufig Antibiotika, zu wenig Impfungen. Internist 2016; 57: 527-531
  • 94 Dalleur O, Spinewine A, Henrard S. et al. Inappropriate prescribing and related hospital admissions in frail older persons according to the STOPP and START criteria. Drugs Aging 2012; 29: 829-837
  • 95 Han BH, Sutin D, Williamson JD. et al. Effect of statin treatment vs usual care on primary cardiovascular prevention among older subjects. The ALLHAT-LLT randomized clinical trial. JAMA Intern Med 2017; 177: 955-965
  • 96 Jerant A, Kravitz RL, Fernandez Y Garcia E. et al. Potential antidepressant overtreatment with office use of brief depression symptom measures. J Am Board Fam Med 2014; 27: 611-620