Picking a PPI: It comes down to cost

,

Applied Evidence

Picking a PPI: It comes down to cost

J Fam Pract. 2008 April;57(4):231-235

By

Patricia R. Wigle, PharmD

No need to be bound to the PPI you’ve always prescribed—efficacy is similar, and all have good adverse-event profiles

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References

1. Top 200 Prescription Drugs of 2006. http://www.pharmacytimes.com/Article.cfm?Menu=1&ID=4629. Accessed August 28, 2007.

2. Berardi RR. A critical evaluation of proton pump inhibitors in the treatment of gastroesophageal reflux disease. Am J Manage Care. 2000;6(suppl):S491-505.

3. Guimaraes EV, Marguet C, Camargos PAM. Treatment of gastroesophageal reflux disease. J Pediatr (Rio J). 2006;82(5 Suppl):S133-145.

4. Hunt RH, Armstrong D, Yaghoobi M, et al. S-tenatoprazole-Na 30 mg, 60 mg and 90 mg versus esomeprazole (ESO) 40 mg in healthy male volunteers (hmv). Gastroenterology. 2007;132:A-488.

5. Klok RM, Postma MJ, Van Hout BA, Brouwers JRBJ. Meta-analysis: comparing the efficacy of proton pump inhibitors in short-term use. Aliment Pharmacol Ther. 2003;17:1237-1245.

6. McDonagh MS, Carson S. Drug Class Review on Proton Pump Inhibitors. 2006. http://www.ohsu.edu/drugeffectiveness/reports/final.cfm. Accessed December 18, 2007.

7. Dachs R, Darby-Stewart A, Graber M. Choosing one PPI treatment over another. Am Fam Phys. 2007;76:1273-1280.

8. Prilosec (package insert). Wilmington, DE: Astra-Zeneca LP; Sep 2006.

9. Prevacid (package insert). Lake Forest, IL: TAP Pharmaceuticals, Inc; Jun 2007.

10. Protonix (package insert). Philadelphia, PA: Wyeth Laboratories; Jun 2007.

11. Aciphex (package insert). Teaneck, NJ: Eisai, Inc; Aug 2003.

12. Nexium (package insert). Wilmington, DE: Astra-Zeneca LP; Apr 2007.

13. Jensen RT. Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas. Basic Clin Pharmacol Toxicol. 2006;98:4-19.

14. Laine L, Ahnen D, McClain C, Solcia E, Walsh JH. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther. 2000;14:651-668.

15. Robinson M. Review article: current perspectives on hypergastrinaemia and enterochromaffin-like cell hyperplasia. Aliment Pharmacol Ther. 1999;13 (Suppl 5):5-10.

16. Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of B12 deficiency in older adults. J Clin Epidemiol. 2004;57:422-428.

17. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947-2953.

18. Gulmez SE, Holm A, Frederiksen H, Jensen TG, Pedersen C, Hallas J. Use of proton pump inhibitors and the risk of community-acquired pneumonia. Arch Intern Med. 2007;167:950-955.

19. Mallow S, Rebuck JA, Osler T, Ahern J, Healey MA, Rogers FB. Do proton pump inhibitors increase the incidence of nosocomial pneumonia and related infectious complications when compared with histamine-2 receptor antagonists in critically ill trauma patients? Curr Surg. 2004;61:452-458.

20. Canani RB, Cirillo P, Roggero P, Romano C, Malamisura B, Terrin G, Passariello A, Manguso F, Morelli L, Guarino A. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006;117:e817-e820.

21. Dial S, Delaney C, Schneider V, Suissa S. Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy. CMAJ. 2006;175:745-748.

22. Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ 2004;171(1):33-38.

23. Lowe DO, Mamdani MM, Kopp A, Low DE, Juurlink DN. Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: a population-based study. Clin Infect Dis. 2006;43:1272-1276.

24. Health Canada reviewing new safety information on cardiac events in patients taking Losec (omeprazole) or Nexium (esomeprazole). http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/2007/2007_95_e.html. Accessed on August 28, 2007.

25. Vanderhoff BT, Tahboub RM. Proton pump inhibitors: an update. Am Fam Phys. 2002;66:273-280.

26. Kuipers EJ, Lundell L, Klinkenberg-Knol EC, et al. Atrophic gastritis and Helicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication. N Engl J Med. 1996;334:1018-1022.

27. Lundell L, Miettinen P, Myrvold HE, et al. Lack of effect of acid suppression therapy on gastric atrophy. Gastroenterology. 1999;117:319-326.

28. Hassall E, Kerr W, El-Serag HB. Characteristics of children receiving proton pump inhibitors continuously for up to 11 years duration. J Pediatr. 2007;150:262-267.

29. Clinical Pharmacology. http://cpip.gsm.com. Accessed on August 17, 2007.

30. Inadomi JM, et al. Step-down management of gastroesophageal disease. Gastroenterology. 2001;121:1095-1100.

31. Tytgat GNJ. Review article: management of mild and severe gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2003;17(Suppl 2):52-56.

32. Ofman JJ, Dorn GH, Fennerty MB, Fass R. The clinical and economic impact of competing management strategies for gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2002;16:261-273.

33. Gerson LB, Robbins AS, Garber A, Hornberger J, Tridafilopoulos G. A cost-effectiveness analysis of prescribing strategies in the management of gastroesophageal reflux disease. Am J Gastroenterol. 2000;95:395-407.

34. Zimmermann AE, Walters JK, Katona BG, Souney PF, Levine D. Review of omeprazole use in the treatment of acid-related disorders in children. Clin Ther. 2001;23:660-679.

35. Humphries TJ, Merritt GJ. Review article: drug interactions with agents used to treat acid-related diseases. Aliment Pharmacol Ther. 1999;23(Suppl 3):18-26.

Rx recommendations

Treatment strategy

Choose the least expensive product available to the patient.
Differences in drug interactions, efficacy, and adverse events are not significant. (A)

Dose and duration

Use PPIs at the lowest effective dose for the minimum duration. (C)
Since many indications for PPI therapy are for a finite duration, attempt to “step down” therapy to a lower dose or try switching to an H2 receptor antagonist periodically, to achieve the goal of minimum effective dose. (C)
If stress ulcer prophylaxis was started in the hospital, re-evaluate the need for continued use of PPIs after hospital discharge. (C)

Safety

PPIs have been on the market for more than 15 years and have a good adverse-event profile, which is comparable to placebo. (A)
Limited data which attempt to link PPIs to several rare adverse events do not establish a cause-effect relationship. (B)

Strength of recommendation (SOR)

Good quality patient-oriented evidence
Inconsistent or limited-quality patient-oriented evidence
Consensus, usual practice, opinion, disease-oriented evidence, case series

THE PATIENT

A 33-year-old man returns to see you about his bothersome heartburn, which tends to occur after lunch and dinner. He says the trouble began about 2 weeks ago. Chewing Tums tablets after meals relieves his symptoms, but he does not like the chalky taste or frequent dosing. He tried OTC Pepcid, but it relieved his symptoms only occasionally. He says he has not lost weight or had nausea, vomiting, bleeding, or dysphagia. Since you saw him the previous month, he has been trying to exercise and watch his diet, to help manage his hypertension, as you advised. His blood pressure has improved, but his heartburn has not.

THE DILEMMA

You decide to start a PPI, but wonder whether there are significant differences in PPIs, and whether there are long-term health consequences.

The last time you wrote a prescription for a proton pump inhibitor, what came to mind? Did you write a prescription for the PPI you always use? Did you prescribe Prilosec because it is available in generic form? Did you decide on Prevacid because the patient had responded well to it before? Did you consider cost, even if the patient was insured? Was your main concern side effects?

Nexium, Prevacid, and Protonix were among the 25 most commonly dispensed medications in 2006.¹ With multiple indications, high clinical efficacy, low incidence of adverse events, convenient dosing, and few drug interactions, it is understandable why PPIs are popular with physicians and patients. Use of prescription PPIs has continued to increase even after Prilosec OTC became available.

TABLES 1–3 give recommended dosing for PPI indications, formulations, drug interactions, cost, and adverse event profiles.

Drug action and efficacy. PPIs have a pharmacokinetic elimination half-life of 30 minutes to 2 hours, but once-daily dosing is possible due to long-lasting inactivation of the proton pump.²

Genetic polymorphism. Up to 6% of Caucasian and 23% of Asian patients are CYP P450 2C19 poor metabolizers.^2,3 This is the common hepatic clearance pathway for currently available PPIs. However, due to PPI efficacy, low potential for drug interactions, and infrequent adverse events, this genetic polymorphism is not likely to affect the vast majority of patients on PPI therapy.

Are differences clinically significant? Many trials have compared PPIs using a variety of surrogate endpoints. A new PPI, S-tenatoprazole [not available in the US] has shown greater acid suppression than esomeprazole.⁴ However, no single agent has proven more efficacious than other PPIs at equipotent doses.^5,6 Even though lansoprazole and omeprazole have the most FDA-approved indications, this should not discourage you from using any PPI for a variety of gastrointestinal indications. For example, lansoprazole and esomeprazole are the only PPIs approved for healing or risk reduction of NSAID-related gastric ulcers. Yet other PPIs have been used for this indication without any reason to suspect lack of effectiveness. A meta-analysis of 41 randomized, double-blind studies evaluated head-to-head clinical trials for many conditions, including Helicobacter pylori, gastroesophageal reflux disease (GERD) and peptic ulcer disease.⁵ No clinically important differences were noted when equipotent doses were used.^5-7

Only 1 difference in the treatment of GERD was noted between esomeprazole 40 mg and omeprazole 20 mg in the pooled results (relative risk 1.18; 95% confidence interval 1.14-1.23). This is not surprising because the 2 medications were not given at equipotent doses.

All PPIs are well tolerated. The most common adverse effects are headache, diarrhea, and abdominal pain.^8-12 The side-effect profile is consistent among PPIs. An exception is dose-related increases in the frequency of diarrhea reported with lansoprazole (ranging from 1.4% to 7.4%) and higher dose omeprazole therapy.^2,8

Although considered relatively safe, several considerations have arisen from clinical trials. Some (occurrence of rebound acid hypersecretion after PPI discontinuation) are better documented than others.¹³ Additional data are needed to determine whether there is any significant association with PPI-induced elevated serum gastrin levels and neoplastic changes or an increased risk of hip fracture, community-acquired pneumonia, Clostridium difficile infection, vitamin B₁₂ anemia, iron malabsorption, and atrophic gastritis (TABLE 3).^13-27