Proton pump inhibitors: side effects and interaction

Česká verzia

Authors: J. Špičák
Authors place of work: Klinika hepatogastroenterologie, IKEM, Praha
Published in the journal: Gastroent Hepatol 2013; 67(4): 289-297
Category: Clinical and Experimental Gastroenterology: Review Article

Summary

Proton pump inhibitors are the most important medicines in the treatment of acid related diseases. All proton pump inhibitors are weak bases being selectively metabolised in the acid environment and blocking the function of active proton pumps. Proton pump inhibitors provide efficient treatment for gastroesophageal reflux disease, Helicobacter pylori eradication, functional dyspepsia and NSAID gastropathy. Proton pump inhibitors differ in pharmacokinetc properties but these differences do not necessarily have clinically relevant consequences. Generally, 2^nd generation proton pump inhibitors provide faster onset of effect, longer gastric secretion inhibition, and specifically the effect of rabeprazole is less dependent on the method of administration and has less influence on the function of the cytochrome P450. The main effect of the 1st generation proton pump inhibitors is modified by the genetic variety of the enzyme CYP2C19 and it is significantly lower in rapid metabolizers. Proton pump inhibitors are very safe and immediate complications are exceptional. They can cause progression of gastritis in Helicobacter infection. In spite of hypergastrinemia they do not have malignant potential. Their long-lasting usage is associated with an increased risk of pelvis and hip fractures, community pneumonia, and clostridium infection. They decrease the effect of antiaggregant therapy with clopidogrel, and increase the risk of recurrent cardiovascular events. The instructions for patients are clearly presented and often important information is lacking.

Key words:
proton pump inhibitors – omeprazole – lansoprazole – pantoprazole – rabeprazole – esomeprazole – side effects – interactions

The author declares he has no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
25. 7. 2013

Accepted:
12. 8. 2013

Zdroje

1. Hatlebakk JG, Katz PO, Camacho-Lobato L et al. Proton pump inhibitors: better acid supression when taken before a meal than without a meal. Aliment Pharmacol Ther 2000; 14(10): 1267–1272.

2. Sachs G. Proton pump inhibitors and acid-related diseases. Pharmacotherapy 1997; 17(1): 22–37.

3. Huang JQ, Hunt RH. Pharmacological and pharmacodynamic essentials of H(2)-receptor antagonists and proton pump inhibitors for the practising physician. Best Pract Res Clin Gastroenterol 2001; 15(3): 355–370.

4. Klotz U. Proton pump inhibitors – their pharmacological impact on the clinical management of acid-related disorders. Arzneimittelforschung 2009; 59(6): 271–282.

5. Satoh H. Discovery of lansoprazole and its unique pharmacological properties independent from anti-secretory activity. Curr Pharm Des 2013; 19(1): 67–75.

6. Moreira Dias L. Pantoprazole: a proton pump inhibitor. Clin Drug Investig 2009; 29 (Suppl 2): 3–12.

7. Martínek J, Lukáš M. Inhibitory protonové pumpy – up to date. Gastroent Hepatol 2011; 65(6): 331–342.

8. Andersson T, Weidolf L. Stereoselective disposition of proton pump inhibitors. Clin Drug Investig 2008; 28(5): 263–279.

9. Horn J. Review article: Understanding the pharmacodynamic and pharmacokinetic differences between proton pump inhibitors – focus on pKa and metabolism. Aliment Pharmacol Ther 2006; 20: 340–350.

10. Marelli S, Pace F. Rabeprazole for the treatment of acid-related disorders. Expert Rev Gastroenterol Hepatol 2012; 6(4): 423–435.

11. Morelli G, Chen H, Rossiter G et al. An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers. Aliment Pharmacol Ther 2011; 33(7): 845–854.

12. Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors. J Neurogastroenterol Motil 2013; 19(1): 25–35.

13. Kukulka M, Eisenberg C, Nudurupati S. Comparator pH study to evaluate the single-dose pharmacodynamics of dual delayed-release dexlansoprazole 60 mg and delayed-release esomeprazole 40 mg. Clin Exp Gastroenterol 2011; 4: 213–220.

14. Li XQ, Andersson TB, Ahlström M et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004; 32(8): 821–827.

15. Friedlander EA, Pallentino J, Miller SK et al. The evolution of proton pump inhibitors for the treatment of gastroesophageal reflux disease. J Am Acad Nurse Pract 2010; 22(12): 674–683.

16. Kirchheiner J, Glatt S, Fuhr U et al. Relative potency of proton-pump inhibitors--comparison of effects on intragastric pH. Eur J Clin Pharmacol 2009; 65(1): 19–31.

17. Klotz U. Clinical impact of CYP2C19 polymorphism on the action of proton pump inhibitors: a review of a special problem. Int J Clin Pharmacol Ther 2006; 44(7): 297–302.

18. Chang YS. Hypersensitivity reactions to proton pump inhibitors. Curr Opin Allergy Clin Immunol 2012; 12(4): 348–353.

19. Lodato F, Azzaroli F, Turco L et al. Adverse effects of proton pump inhibitors. Best Pract Res Clin Gastroenterol 2010; 24(2): 193–201.

20. Malfertheiner P, Megraud F, O´Morain CA et al. Management of Helicobacter pylori infection – the Maastricht IV/ /Florence Consensus Report. Gut 2012; 61(5): 646–664.

21. Fiocca R, Mastracci L, Attwood SE et al. Gastric exocrine and endocrine cell morphology under prolonged acid inhibition therapy: results of a 5-year follow-up in the LOTUS trial. Aliment Pharmacol Ther 2012; 36(10): 959–971.

22. Laheij RJ, Sturkenboom MC, Hassing RJ et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 2004; 292(16): 1955–1960.

23. Jalving M, Koornstra JJ, Wesseling J et al. Increased risk of fundic gland polyps during long-term proton pump inhibitor therapy. Aliment Pharmacol Ther 2006; 24(9): 1341–1348.

24. Thomson AB, Sauve MD, Kassam N et al. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol 2010; 16(19): 2323–2330.

25. Wright MJ, Sullivan RR, Gaffney--Stomberg E et al. Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial. J Bone Miner Res 2010; 25(10): 2205–2211.

26. Hansen KE, Jones AN, Lindstrom MJ et al. Do proton pump inhibitors decrease calcium absorption? J Bone Miner Res 2010; 25(12): 2786–2795.

27. Yu EW, Bauer SR, Bain PA et al. Proton pump inhibitors and risk of fractures: a meta--analysis of 11 international studies. Am J Med 2011; 124(6): 519–526.

28. Khalili H, Huang ES, Jacobson BC et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study. BMJ 2012; 344: e372.

29. Targownik LE, Leslie WD, Davison KS et al. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos). Am J Gastroenterol 2012; 107(9): 1361–1369.

30. Jefferies KC, Cipriano DJ, Forgac M. Function, structure and regulation of the vacuolar (H+)-ATPases. Arch Biochem Biophys 2008; 476(1): 33–42.

31. U.S. Food and Drug Administration. Postmarket Drug Safety Information for Patients and Providers. Available from: http:/www.fda.gov/drugssafety/postmarketdrugssafetyinformationforpatientsandproviders/ucm2132056htm.

32. Shabajee N, Lamb EJ, Sturgess I et al. Omeprazole and refractory hypomagnesaemia. BMJ 2008; 337: a425.

33. Yang YX, Metz DC. Safety of proton pump inhibitor exposure. Gastroenterology 2010; 139(4): 1115–1127.

34. U.S. Food and Drug Administration. FDA Drug Safety Communication: Low magnesium levels can be associated with long--term use of Proton Pump Inhibitor drugs (PPIs). Available from: http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm.

35. Sultan N, Nazareno J, Gregor J et al. Association between proton pump inhibitors and respiratory infections: a systematic review and meta-analysis of clinical trials. Can J Gastroenterol 2008; 22(9): 761–766.

36. Eom CS, Jeon CY, Lim JW et al. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ 2011; 183(3): 310–319.

37. Giuliano C, Wilhelm SM, Kale-Pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol 2012; 5(3): 337–344.

38. Sarkar M, Hennessy S, Yang YX. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med 2008; 149(6): 391–398.

39. Cunningham R, Dale B, Undy B et al. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. J Hosp Infect 2003; 54(3): 243–245.

40. Khanna S, Aronson SL, Kammer PP et al. Gastric acid suppression and outcomes in Clostridium difficile infection: a population-based study. Mayo Clin Proc 2012; 87(7): 636–642.

41. Deshpande A, Pant C, Pasupuleti V et al. Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clin Gastgroenterol Hepatol 2012; 10(3): 225–233.

42. Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol 2013; 11(5): 483–490.

43. Bajaj JS, Zadvornova Y, Heuman DM et al. Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patiens with ascites. Am J Gastroenterol 2009; 104(5): 1130–1134.

44. Campbell MS, Obstein K, Reddy KR et al. Association between proton pump inhibitor use and spontaneous bacterial peritonitis. Dig Dis Sci 2008; 53(2): 394–398.

45. Trikudanathan G, Israel J, Cappa J et al. Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients – a systematic review and meta-analysis. Int J Clin Pract 2011; 65(6): 674–678.

46. Ogawa R, Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet 2010; 49(8): 509–533.

47. Johnson DA, Oldfield EC 4th. Reported side effects and complications of long-term proton pump inhibitor use: dissecting the evidence. Clin Gastroenterol Hepatol 2013; 11(5): 458–464.

48. Hulot JS, Collet JP, Silvain J et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration: a systematic meta-analysis. J Am Coll Cardiol 2010; 56(2): 134–143.

49. Parri MS, Gianetti J, Dushpanova A et al. Pantoprazole significantly interferes with antiplatelet effect of clopidogrel: Results of a pilot randomized trial. Int J Cardiol 2012.

50. Drepper MD, Spahr L, Frossard JL. Clopidogrel and proton pump inhibitors – where do we stand in 2012? World J Gastroenterol 2012; 18(18): 2161–2171.

51. Chen J, Yuan YC, Leontiadis GI et al. Recent safety concerns with proton pump inhibitors. J Clin Gastroenterol 2012; 46(2): 93–114.

52. Bhatt DL, Cryer BL, Contant CF et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363(20): 1909–1917.

53. Uotani T, Sugimoto M, Nishino M et al. Ability of rabeprazole to prevent gastric mucosal damage from clopidogrel and low doses of aspirin depends on CYP2C19 genotype. Clin Gasteroenterol Hepatol 2012; 10(8): 879–885.

54. El-Halabi MM, Zgheib N, Mansour NM et al. CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel. J Cardiovasc Pharmacol 2013; 62(1): 41–49.

55. Frelinger AL 3rd, Lee RD, Mulford DJ et al. A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and phartmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol 2012; 59(14): 1304–1311.

56. Petersen KU. Relevance of metabolic activation pathways: the example of clopidogrel and prasugrel. Arzneimittelforschung 2009; 59(5): 213–227.

57. O'Donoghue ML, Braunwald E, Antman EM et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009; 374(9694): 989–997.