Esomeprazole for Injection

06 January 2009

Products Affected - Description

Esomeprazole for Injection (Nexium I.V.), AstraZeneca
20 mg single dose vials, package of 10 (NDC 00186-6020-01)

Lansoprazole for injection (Prevacid I.V.), TAP Pharmaceuticals - discontinued
30 mg single dose vials, package of 10 (NDC 00300-3954-25)

Reason for the Shortage

• Nexium I.V. had been in short supply due to increased demand for product.¹
• TAP Pharmaceuticals discontinued Prevacid I.V. in 2007.²

Estimated Resupply Dates

• AstraZeneca has available the 40 mg single dose vial (NDC 00186-6040-01) and the 20 mg single dose vial (NDC 00186-6020-01).¹ Oral Nexium is available.
• Wyeth has pantoprazole injection (Protonix I.V.) available.³

Implications for Patient Care

• Esomeprazole injection is labeled for the short-term treatment (up to 10 days) of erosive esophagitis, as an alternative to oral medications.⁴
• Pantoprazole injection is labeled for the short-term treatment (7 to 10 days) of gastroesophageal reflux disease (GERD) associated with erosive esophagitis as an alternative to oral therapy in patients who are unable to take pantoprazole delayed-release tablets.⁵ Pantoprazole injection is also labeled for the treatment of pathological hypersecretory conditions associated with neoplasia, such as Zollinger-Ellison syndrome.⁵
• While not among the FDA-approved indications, the injectable proton pump inhibitors are also used to treat gastrointestinal bleeding and prevent gastrointestinal rebleeding.^6-7

Safety

• Pantoprazole injection contains edetate disodium (EDTA), which is a potent chelator of zinc. For patients prone to zinc deficiency, zinc supplementation should be considered while patients are receiving IV pantoprazole.⁵
• The dose of IV esomeprazole is different from the dose of IV pantoprazole.^4,5

Alternative Agents & Management

• During this shortage, clinicians may consider using other injectable proton-pump inhibitors, injectable histamine H₂-receptor antagonists, or oral proton pump inhibitor (PPI) preparations. Table 1 provides alternatives to esomeprazole injection for selected clinical situations.
• Dosage equivalences among the oral PPIs have been established in clinical trials. The following doses administered at the same interval give approximately equivalent therapeutic results: esomeprazole 20 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, or rabeprazole 20 mg.⁸ A 40-mg dose of pantoprazole IV is approximately equivalent to a 40-mg oral dose.⁵
• Oral esomeprazole, lansoprazole, omeprazole, and pantoprazole may be given by the enteral route to patients with a swallowing difficulty or enteral feeding tube.^9-13 Rabeprazole is formulated as delayed-release, enteric-coated tablet and cannot be crushed.¹⁴
• Special procedures must be used for administering these agents by feeding tubes, as shown in Table 2. Use of simplified oral suspensions may be a preferred method both for convenience and to avoid tube clogging. Simplified PPI suspensions are effective when administered into the stomach, although some drug degradation may occur.^15,16 When maximal efficacy is required, simplified PPI suspensions should be administered only into the intestine (ie, Dobhoff®, Miller-Frederick®) and intact granules should be administered only into the stomach (ie, 8 French or larger NG or G tube).^{17, 18} See Table 3 for further information on simplified suspensions.

Related Shortages

• Lansoprazole Injection— No Longer Available
• Omeprazole Tablets— Resolved
• Pantoprazole Sodium Injection— Resolved
• Ranitidine Injection

1. AstraZeneca, (personal communications). August 20, September 3 and 16, October 27, and December 10, 2008; and January 6, 2009.
2. TAP Pharmaceuticals, (personal communications). July 30, 2007.
3. Wyeth, (personal communication). August 20, September 16, October 27, and December 10, 2008; and January 6, 2009.
4. Nexium I.V. [product information]. Wilmington, DE: AstraZeneca; April 2007.
5. Protonix I.V. [product information]. Philadelphia, PA: Wyeth Laboratories; December 2007.
6. Boparai V, Rajagopalan J, Triadafilopoulos G. Guide to the use of proton pump inhibitors in adult patients. Drugs. 2008;68(7):925-947.
7. Sung JJ, Mossner J, Barkun A, et al. Intravenous esomeprazole for prevention of peptic ulcer re-bleeding: rationale/design of Peptic Ulcer Bleed study. Aliment Pharmacol Ther. Apr 2008;27(8):666-677.
8. Williams DB, Schade RR. Gastroesophageal Reflux Disease. In: Dipiro, JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy, A Pathologic Approach. 6th Ed. New York, NY: McGraw Hill; 2005: 613-28.
9. Nexium oral [product information]. Wilmington, DE: AstraZeneca; February 2008.
10. Prevacid [product information]. Lake Forest, IL: TAP Pharmaceuticals; July 2007.
11. Prilosec [product information]. Wilmington, DE: AstraZeneca; March 2008.
12. Zegerid [product information]. San Diego, CA: Santarus, Inc.; January 2008.
13. Protonix oral [product information]. Philadelphia, PA: Wyeth Laboratories; May 2008.
14. Aciphex [product information]. Woodcliff Lake, NJ: Eisai Inc.; June 2008.
15. Sharma VK, Vasudeva R, Howden CW. Simplified lansoprazole suspension—a liquid formulation of lansoprazole—effectively suppresses intragastric acidity when administered through a gastrostomy. Am J Gastroenterol. 1999;94:1813-1817.
16. Phillips JO, Metzler MH. The stability of simplified lansoprazole suspension (SLS). Gastroenterology. 1999;116(4 part 2):A89.
17. Song JC, Quercia RA, Fan C, Tsikouris J, White CM. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Am J Health-Syst Pharm. 2001;58:689-694.
18. Sharma VK, Peyton B, Spears T, Raufman JP, Howden CW. Oral pharmacokinetics of omeprazole and lansoprazole after single and repeated doses as intact capsules or as suspensions in sodium bicarbonate. Aliment Pharmacol Ther. 2000;14:887-892.
19. McEvoy GK, ed. Antiulcer agents and acid suppressants. AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2008:3009-3058.
20. Bajaj JS, Dua KS, Hanson K, Presberg K. Prospective, randomized trial comparing effect of oral versus intravenous pantoprazole on rebleeding after nonvariceal upper gastrointestinal bleeding: a pilot study. Dig Dis Sci. Sep 2007;52(9):2190-2194.
21. Hartmann D, Eickhoff A, Damian U, Riemann JF, Schilling D. Effect of intravenous application of esomeprazole 40 mg versus pantoprazole 40 mg on 24-hour intragastric pH in healthy adults. Eur J Gastroenterol Hepatol. Feb 2007;19(2):133-137.
22. Tsibouris P, Zintzaras E, Lappas C, et al. High-dose pantoprazole continuous infusion is superior to somatostatin after endoscopic hemostasis in patients with peptic ulcer bleeding. Am J Gastroenterol. Jun 2007;102(6):1192-1199.
23. Zargar SA, Javid G, Khan BA, et al. Pantoprazole infusion as adjuvant therapy to endoscopic treatment in patients with peptic ulcer bleeding: prospective randomized controlled trial. J Gastroenterol Hepatol. Apr 2006;21(4):716-721.
24. Rohss K, Wilder-Smith C, Kilhamn J, Fjellman M, Lind T. Suppression of gastric acid with intravenous esomeprazole and omeprazole: results of 3 studies in healthy subjects. Int J Clin Pharmacol Ther. Jun 2007;45(6):345-354.
25. Armstrong D. Intravenous proton pump inhibitor therapy: a rationale for use. Rev Gastroenterol Disord. 2005;5 Suppl 2:S18-30.
26. Beejay U, Wolfe MM. Acute gastrointestinal bleeding in the intensive care unit. Gastroenterology Clinics. 2000;29(2):309-336.
27. Reynolds MS, Petros BA. H2-Antagonists: Continuous infusion for Stress Ulcer Prophylaxis (Drug Consult). In: Klasco RK (Ed): DRUGDEX® System (electronic version). Thomson Micromedex, Greenwood Village, Colorado, USA. (cited: August 20, 2008).
28. Donnelly AJ, Baughman VL, Gonzales JP, et al. Anesthesiology and Critical Care Drug Handbook. 6th ed. Hudson, OH: Lexi-Comp; 2005.
29. American Society of Health-System Pharmacists. ASHP therapeutic guidelines on stress ulcer prophylaxis. Am J Health-Syst Pharm. 1999;56:347-379.
30. Leontiadis GI, Sreedharan A, Dorward S, et al. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technol Assess. Dec 2007;11(51):iii-iv, 1-164.
31. AstraZeneca Medical Information. Nexium-alternate methods of administration [written communication]. August 21, 2008.
32. White CW, Kalus JS, Quercia R, Fortier C, et al. Delivery of esomeprazole magnesium enteric-coated pellets through small caliber and standard nasogastric tubes and gastrostomy tubes in vitro. Am J Health-Syst Pharm. 2002;59(1):2085-8.
33. Sostek MB, Chen Y, Skammer W, Winter H et al. Esomeprazole administered through a nasogastric tube provides bioavailability similar to oral dosing. Aliment Pharmacol Ther 2003;18:581-6.
34. DiGiacinto JL, Olsen KM, Bergman KL, Hoie EB. Stability of suspension formulations of lansoprazole and omeprazole stored in amber-colored plastic oral syringes. Ann Pharmacother. 2000;34:600-605.
35. McAndrews KL, Eastham JH. Omeprazole and lansoprazole suspensions for nasogastric administration. Am J Health-Syst Pharm. 1999;56:81.
36. Phillips JO, Metzler MH, Palmieri TL, Huckfeldt RE, Dahl NG. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Crit Care Med. 1996;24:1793-1800.
37. Safety briefs. ISMP Medication Safety Alert! 2002; 7(12):1-2.
38. Quercia RA, Fan C, Liu X, Chow MSS. Stability of omeprazole in an extemporaneously prepared oral liquid. Am J Health-Syst Pharm. 1997;54:1833-1836.
39. Ferron GM, Ku Sherry, Abell M, et al. Oral bioavailability of pantoprazole suspended in sodium bicarbonate solution. Am J Health-Syst Pharm. 2003; 60:1324-9.
40. Zimmermann A, Walters JK, Katona B, Souney P. Alternative methods of proton pump inhibitor administration. Consult Pharm. 1997;12:990-998.

Updated

Updated January 6, 2009 by Michelle Wheeler, Pharm.D., Drug Information Specialist. Created August 21, 2008 by Jane Chandramouli, Pharm.D., Drug Information Specialist. Copyright 2008, Drug Information Service, University of Utah, Salt Lake City, UT.

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