Proton Pump Inhibitor Formulary Considerations in the Acutely Ill Part 2: Clinical Efficacy,Safety,and Economics

Abstract

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French

OBJECTIVE

To review, using an evidence-based approach, the clinical efficacy, safety, and cost-effectiveness of proton pump inhibitors (PPIs) for treatment of common acid peptic disorders in the acutely ill and provide clinicians with guidance when making hospital formulary decisions with this class of agents.

DATA SOURCES

MEDLINE (1966–May 2005) and the Cochrane Library databases were searched using the key words proton pump inhibitor, acid suppression, peptic ulcer disease, gastrointestinal bleeding, stress ulcer prophylaxis, critical care, safety, and cost-effectiveness. Bibliographies of cited references were reviewed, and a manual search of abstracts from recent gastroenterology, critical care, and surgery scientific meetings was completed.

STUDY SELECTION AND DATA EXTRACTION

All articles identified from the data sources were evaluated, and all information deemed relevant was included for this review.

DATA SYNTHESIS

PPIs have become a mainstay for acute acid suppression in hospitalized patients. Various commercially available PPI products are available either enterally or parenterally for administration to patients unable to swallow a tablet or capsule. The results of studies comparing the clinical efficacy of different PPI dosage forms and routes of administration, safety considerations, and cost-effectiveness analyses are among the factors to consider when making formulary decisions for this class of drugs.

CONCLUSIONS

While the introduction of new PPI products has expanded the therapeutic options for acid suppression in acutely ill patients, a number of unresolved questions remain surrounding the interchangeability of these products, the clinical significance of one PPI formulation over the other, and how oral/enteral therapy should be used as step-down therapy after parenteral therapy.

Keywords

proton pump inhibitors esomeprazole lansoprazole omeprazole pantoprazole rabeprazole stress ulcer prophylaxis

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References

1. Welage

, Berardi

. Evaluation of omeprazole, lansoprazole, pantoprazole and rabeprazole in the treatment of acid-related disorders. J Am Pharm Assoc 2000; 40: 52–62.

2. Metz

, Pratha

, Martin

, Paul

, Maton

, Lew

, Oral and intravenous dosage forms of pantoprazole are equivalent in their ability to suppress gastric acid secretion in patients with gastroesophageal reflux disease. Am J Gastroenterol 2000; 95: 626–33.

3. Pisegna

. Pharmacology of acid suppression in the hospital setting: focus on proton pump inhibition. Crit Care Med 2002; 30 (suppl): S356–61.

4. Conrad

. Acute upper gastrointestinal bleeding in critically ill patients: causes and treatment modalities. Crit Care Med 2002; 30 (suppl): S365–8.

5. Hellstrom

, Vitols

. The choice of proton pump inhibitor: does it matter? Basic Clin Pharmacol Toxicol 2004; 94: 106–11.

6. Pisegna

. Switching between intravenous and oral pantoprazole. J Clin Gastroenterol 2001; 32: 27–32.

7. Zuckerman

. A prescription for sanity. US News World Rep 2004;(Nov 22)137: 80.

8. Kaplan

, Bates

, McDonald

. Inappropriate use of intravenous proton pump inhibitors: problem extent and cost implications (abstract). Am J Gastroenterol 2002; 97 (suppl): S236.

9. Enns

, Andrews

, Fishman

, Hahn

, Atkinson

, Kwan

, Description of prescribing practices in patients with upper gastrointestinal bleeding receiving intravenous proton pump inhibitors: a multicenter study. Can J Gastroenterol 2004; 18: 561–71.

10.

10. Cornish

, Papastergiou

, Saibil

. Audit of IV pantoprazole: patterns of use and compliance with guidelines. Can J Hosp Pharm 2002; 55: 20–6.

11.

11. Devlin

, Welage

, Olsen

. Proton pump inhibitor formulary considerations in the acutely ill. Part 1: Pharmacology, pharmacodynamics, and available formulations. Ann Pharmacother 2005_____

12.

12. Package insert. Nexium (esomeprazole). Wilmington, DE: AstraZeneca PLC. www.astrazeneca-us.com/pi/Nexium.pdf (accessed 2005 May 12).

13.

13. Package insert. Prevacid (lansoprazole). Lake Forest, IL: TAP Pharmaceutical Products. www.pitap.abbott.com/prevacid.pdf (accessed 2005 May 12).

14.

14. Package insert. Prilosec (omeprazole). Wilmington, DE: AstraZeneca PLC. www.astrazeneca-us.com/pi/Prilosec.pdf (accessed 2005 May 12).

15.

15. Package insert. Aciphex (rabeprazole). Titusville, NJ: Janssen Pharmaceutica. www.janssen.com/active/janus/en_US/assets/jan/aciphex.pdf (accessed 2005 May 12).

16.

16. Package insert. Protonix (pantoprazole) delayed release tablet. Madison, WI: Wyeth Pharmaceuticals. www.wyeth.com/content/ShowLabeling.asp?id=135 (accessed 2005 May 12).

17.

17. DeVault

, Castell

, for the American College of Gastroenterology. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol 2005; 100: 190–200.

18.

18. Peura

. Prevention of nonsteroidal anti-inflammatory drug–associated gastrointestinal symptoms and ulcer complications. Am J Med 2004; 117 (suppl): 63S–71S.

19.

19. Package insert. Zegerid (omeprazole). San Diego: Santarus. www.santarus.com/pdf/package_insert.pdf (accessed 2005 May 12).

20.

20. Package insert. Protonix IV (pantoprazole). Madison, WI: Wyeth Pharmaceuticals. www.wyeth.com/content/ShowLabeling.asp?id=469 (accessed 2005 May 12).

21.

21. Package insert. Prevacid IV (lansoprazole). Lake Forest, IL: TAP Pharmaceutical Products. www.pitap.abbott.com/prevacidiv.pdf (accessed 2005 May 12).

22.

22. Kovacs

, Lee

, Chiu

, Pilmer

, Metz

. Intravenous and oral lansoprazole are equivalent in suppressing stimulated acid output in patient volunteers with erosive oesophagitis. Aliment Pharmacol Ther 2004; 20: 883–9.

23.

23. Package insert. Nexium IV (esomeprazole). Wilmington, DE: AstraZeneca PLC. www.astrazeneca-us.com/pi/Nexium.pdf (accessed 2005 May 12).

24.

24. Schneider

, Van Rensburg

, Schmidt

, Aboo

, Makela

, Naucler

, Esomeprazole 40 mg administered intravenously has similar safety and efficacy profiles to the oral formulation in patients with erosive esophagitis. Digestion 2004; 70: 250–6.

25.

25. Hung

, Schubert

, Mihas

. Zöllinger–Ellison syndrome. Curr Treat Options Gastroenterol 2003; 6: 163–70.

26.

26. Lew

, Pisegna

, Starr

, Soffer

, Forsmark

, Modlin

, Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zöllinger–Ellison syndrome. Gastroenterology 2000; 118: 696–704.

27.

27. Metz

, Forsmark

, Lew

, Starr

, Soffer

, Bochenek

, Replacement of oral proton pump inhibitors with intravenous pantoprazole to effectively control gastric acid hypersecretion in patients with Zöllinger–Ellison syndrome. Am J Gastroenterol 2001; 96: 3274–80.

28.

28. Schumann

, Schuster

, Zuckerman

. Prophylactic therapy for stress ulcer bleeding: a reappraisal. Ann Intern Med 1987; 106: 562–7.

29.

29. Cook

, Fuller

, Guyatt

, Marshall

, Leasa

, Hall

, Risk factors for gastrointestinal bleeding in critically ill patients. N Engl J Med 1994; 330: 377–81.

30.

30. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. Am J Health Syst Pharm 1999; 56: 347–79.

31.

31. Daley

, Rebuck

, Welage

, Rogers

. Prevention of stress ulceration: current trends in critical care. Crit Care Med 2004; 32: 2008–13.

32.

32. Lam

, Le

, Crawford

, Patel

. National survey of stress ulcer prophylaxis. Crit Care Med 1999; 27: 98–103.

33.

33. Martin

, Booth

, Karlstadt

, Silverstein

, Jacobs

, Hampsey

, Continuous intravenous cimetidine decreases stress-related upper gastrointestinal hemorrhage without promoting pneumonia. Crit Care Med 1993; 21: 19–30.

34.

34. Phillips

, Metzler

, Palmieri

, Huckfeldt

, Dahl

. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Crit Care Med 1996; 24: 1793–800.

35.

35. Lasky

, Metzler

, Phillips

. A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients. J Trauma 1998; 44: 527–33.

36.

36. Roberts

, Pitcher

, Cryer

. Effect of lansoprazole suspension versus continuous intravenous ranitidine on gastric pH of mechanically ventilated intensive care unit patients (abstract). Crit Care Med 2000; 28: 567.

37.

37. Phillips

, Metzler

, Huckfeldt

, Olsen

. A multicenter, prospective, randomized clinical trial of continuous infusion I.V. ranitidine vs. omeprazole suspension in the prophylaxis of stress ulcers (abstract). Crit Care Med 1998; 26 (suppl): A101.

38.

38. Levy

, Seelig

, Robinson

, Ranney

. Comparison of omeprazole and ranitidine for stress ulcer prophylaxis. Dig Dis Sci 1997; 42: 1255–9.

39.

39. Jung

, MacLaren

. Proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. Ann Pharmacother 2002; 36: 1929–37. DOI 10.1345/aph.1C151

40.

40. Conrad

, Gabrielli

, Margolis

, Quartin

, Hata

, Frank

, Randomized, double-blind comparison of immediate-release omeprazole-oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients. Crit Care Med 2005; 33: 760–5.

41.

41. Welage

, Ellis

, Alaniz

. Gastrointestinal alterations in the critically ill. Pharm Pract News 2003; 7 (8): 46–51.

42.

42. Somberg

, Karlstadt

, Blatcher

. Intermittent intravenous pantoprazole maintains control of gastric pH in intensive care unit patients (abstract). Am J Gastroenterol 2002; 97 (suppl): S47.

43.

43. Barkun

, Bardou

, Marshall

. Nonvariceal Upper GI Bleeding Consensus Conference Group. Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 2003; 139: 843–57.

44.

44. Green

, Kaplan

, Curtis

, Levine

. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor to prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978; 74: 38–43.

45.

45. Levine

, Leontiadis

, Sharma

, Howden

. Meta-analysis: the efficacy of intravenous H₂-receptor antagonists in bleeding peptic ulcer. Aliment Pharmacol Ther 2002; 16: 1137–42.

46.

46. Leontiadis

, McIntyre

, Sharma

, Howden

. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database Syst Rev 2004; (3): CD002094.

47.

47. Lau

, Leung

, Wu

, Chan

, Wong

, Hung

, Early administration of high-dose intravenous omeprazole prior to endoscopy in patients with upper gastrointestinal bleeding: a double-blind, placebo-controlled, randomized trial (abstract 347). Presented at: 2005 Digestive Disease Week Meeting, Chicago, IL, May 15–18, 2005.

48.

48. Erstad

. Proton-pump inhibitors for acute peptic ulcer bleeding. Ann Pharmacother 2001; 35: 730–40. DOI 10.1345/aph.10306

49.

49. Daneshmend

, Hawkey

, Langman

, Logan

, Long

, Walt

. Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. BMJ 1992; 304: 143–7.

50.

50. Villanueva

, Balanzo

, Torras

, Sainz

, Soriano

, Gonzalez

, Omeprazole versus ranitidine as adjunct therapy to endoscopic injection in actively bleeding ulcers: a prospective and randomized study. Endoscopy 1995; 27: 308–12.

51.

51. Lau

, Sung

, Lee

, Yung

, Wong

, Wu

, Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med 2000; 343: 310–6.

52.

52. Barkun

, Racz

, van Rensburg

, Beglinger

, Kupcinskas

, Schaefer-Preuss

, Prevention of peptic ulcer rebleeding using continuous infusion of pantoprazole vs ranitidine: a multicenter, multinational, randomized, double-blind, parallel-group comparison (abstract). Gastroenterology 2004; 126: A78.

53.

53. Hsu

, Lo

, Lin

, Chan

, Wu

, Intravenous pantoprazole versus ranitidine for prevention of rebleeding after endoscopic hemostasis of bleeding peptic ulcers. World J Gastroenterol 2004; 10: 3666–9.

54.

54. Chan

, Goebig

, Demers

, Katzka

, Metz

. Intravenous pantoprazole to prevent rebleeding after endoscopic hemostasis of bleeding ulcers: initial U.S. experience (abstract). Gastroenterology 2003; 124 (4 suppl 1): A626.

55.

55. Khuroo

, Yattoo

, Javid

, Khan

, Shah

, Gulzar

, A comparison of omeprazole and placebo for bleeding peptic ulcer. N Engl J Med 1997; 336: 1054–8.

56.

56. Javid

, Masoodi

, Zargar

, Khan

, Yatoo

, Shah

, Omeprazole as adjuvant therapy to endoscopic combination injection sclerotherapy for treating bleeding peptic ulcer. Am J Med 2001; 111: 280–4.

57.

57. Kaviani

, Hashemi

, Kazemifar

, Roozitalab

, Mostaghni

, Merat

, Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: a prospective, double-blind, randomized, clinical trial. Aliment Pharmacol Ther 2003; 17: 211–6.

58.

58. Nguyen

, Barletta

, Devlin

. Use of acid suppression agents following acute, non-variceal, upper gastrointestinal bleeding. Hosp Pharm 2004; 39: 970–5.

59.

59. McAndrews

Jr , Eastham

. Omeprazole and lansoprazole suspensions for nasogastric administration. Am J Health Syst Pharm 1999; 56: 81.

60.

60. Sandvik

, Brenna

, Waldum

. The pharmacologic inhibition of gastric acid secretion—tolerance and rebound. Aliment Pharmacol Ther 1997; 11: 1013–8.

61.

61. Dial

, Alrasadi

, Manoukian

, Huang

, Menzies

. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case–control studies. CMAJ 2004; 171: 33–8.

62.

62. Navab

, Steingrub

. Stress ulcer: is routine prophylaxis necessary? Am J Gastroenterol 1995; 90: 708–12.

63.

63. Cook

, Guyatt

, Marshall

, Leasa

, Fuller

, Hall

, A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. N Engl J Med 1998; 338: 791–7.

64.

64. Laheij

, Sturkenboom

, Hassing

, Dieleman

, Stricker

, Jansen

. Risk of community-acquired pneumonia and use of gastric acid–suppressive drugs. JAMA 2004; 292: 1955–60.

65.

65. Stedman

, Barclay

. Comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors. Aliment Pharmacol Ther 2000; 14: 963–78.

66.

66. Andersson

, Hassan-Alin

, Hasselgren

, Rohss

. Drug interaction studies with esomeprazole, the (S)-isomer of omeprazole. Clin Pharmacokinet 2001; 40: 523–37.

67.

67. Welage

. Pharmacologic properties of the proton pump inhibitors: comparing the agents. Pharmacotherapy 2003; 23 (suppl): 74S–80S.

68.

68. Welage

, Berardi

. Drug interactions with antiulcer agents: considerations in the treatment of acid-peptic disease. J Pharm Pract 1994; 6: 177–95.

69.

69. Andersson

, Andren

, Cederberg

, Lagerstrom

, Lundborg

, Skanberg

. Pharmacokinetics of omeprazole after single and repeated oral administration in healthy subjects. Br J Clin Pharmacol 1990; 29: 557–63.

70.

70. Hassan-Alin

, Andersson

, Bredberg

, Rohss

. Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects. Eur J Clin Pharmacol 2000; 56: 665–70.

71.

71. Schupp

, Schrand

, Mutnick

. A cost-effectiveness analysis of stress ulcer prophylaxis. Ann Pharmacother 2003; 37: 631–5. DOI 10.1345/aph.1C377

72.

72. Lee

, You

, Wong

, Kwong

, Lau

, Chan

, Cost-effectiveness analysis of high-dose omeprazole infusion as adjuvant therapy to endoscopic treatment of bleeding peptic ulcer. Gastrointest Endosc 2003; 57: 160–4.

73.

73. Spiegel

, Ofman

, Woods

, Vakil

. Minimizing recurrent peptic ulcer hemorrhage after endoscopic hemostasis: the cost-effectiveness of competing strategies. Am J Gastroenterol 2003; 98: 86–97.

74.

74. Barkun

, Herbá

, Adam

, Kennedy

, Fallone

, Bardou

, High-dose intravenous proton pump inhibition following endoscopic therapy in the acute management of patients with bleeding peptic ulcers in the USA and Canada: a cost-effectiveness analysis. Aliment Pharmacol Ther 2004; 19: 591–600.

75.

75. Enns

, Gagnon

, Rioux

, Levy

. Cost-effectiveness in Canada of intravenous proton pump inhibitors for all patients presenting with acute upper gastrointestinal bleeding. Aliment Pharmacol Ther 2003; 17: 225–33.

76.

76. Gagnon

, Levy AR Eloubeidi

. Cost implications of administering intravenous proton pump inhibitors to all patients presenting to the emergency department with peptic ulcer bleeding. Value Health 2003; 6: 457–65.

77.

77. Erstad

. Cost-effectiveness of proton pump inhibitor therapy for acute peptic ulcerrelated bleeding. Crit Care Med 2004; 32: 1277–83.

78.

78. Devlin

, Welage

. The cost-effectiveness of proton pump inhibitors for bleeding peptic ulcers: the unanswered questions. Crit Care Med 2004; 32: 1415.