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Pancreatic Enzyme Replacement Products containing Lipase, Protease, and Amylase

Last Updated: December 12, 2012
Status: Resolved

Products Affected - Description

Unapproved products
Lipase / Protease / Amylase pancreatic enzyme replacement products; Ethex, Major, X-Gen, various – discontinued
Creon 5, Creon 10, Creon 20; Solvay – discontinued
Pangestyme; Ethex – discontinued
Pancrease MT 4, Pancrease MT 10, Pancrease MT 16, Pancrease MT 20; Johnson Ortho McNeil
Pancrecarb MS-4, Pancrecarb MS-8, Pancrecarb MS-16; Digestive Care
Ultrase; Axcan Scandipharm
Ultrase MT12, Ultrase MT18, Ultrase MT20; Axcan Scandipharm
Viokase 8, Viokase 16; Axcan Scandipharm

Reason for the Shortage

  • FDA issued a mandate in 2004 requiring manufacturers of pancreatic enzyme replacement products to seek approval through the New Drug Application (NDA) process, in response to concerns about potential for patient harm and lack of ingredient standardization. At that time, all marketed pancreatic enzyme products were unapproved drugs. The manufacturers were given until April 28, 2010 to obtain NDA approval, in order to continue marketing their products. In addition, manufacturers are required to implement risk evaluation and management strategy (REMS) programs and a Medication Guide must be dispensed to the patient with each new or refill prescription.1-3
  • Solvay discontinued their unapproved Creon Minimicrospheres products in 2009. They will continue marketing their FDA-approved Creon product.4-7
  • X-Gen stopped distributing their unapproved pancreatic enzyme replacement products in November 2009, although they now distribute an authorized generic product.8-10
  • Several other manufacturers have discontinued their unapproved pancreatic enzyme replacement products, including Ethex and Major.

Estimated Resupply Dates

  • Unapproved pancreatic enzyme replacement products other than Pancrease MT may not be marketed or distributed after April 28, 2010.1-3,11
  • There are no approved pancreatic enzyme powders.
  • Solvay has available the new FDA-approved formulation of Creon.4-7
  • Eurand has FDA-approved Zenpep available.12,13
  • X-Gen has available the 5,000 unit strength of Zenpep as an authorized generic product.8-10
  • Pancrease MT products may no longer be distributed by wholesalers or dispensed by pharmacies and health-care systems. McNeil Pediatrics has the new FDA-approved formulation of Pancreaze available. Now that Pancreaze is available, pharmacies and health-care systems should return any remaining inventory of Pancrease MT to the manufacturer.11,14-16
  • Aptalis has received FDA approval for Ultresa and Viokace. Both Viokace and Ultresa are available.17-19
  • Digestive Care has received FDA approval for Pertzye. This product is available.20,21

Implications for Patient Care

  • Pancreatic enzyme replacement products are labeled for the treatment of pancreatic enzyme deficiency caused by cystic fibrosis or other disorders.6,8,12 Patients currently receiving therapy with unapproved pancreatic enzyme replacement products will need to switch to an FDA-approved product.22
  • Six pancreatic enzyme replacement products have been FDA-approved. Creon and Zenpep were approved in 2009.1-7,9,12 Pancreaze was approved in April 2010,11,14,15 Ultresa and Viokace were approved in March 2012,17,18 and Pertzye was approved in May 2012. These are the only FDA-approved products, although they are not AB-rated to each other.23
  • X-Gen distributes the 5,000 unit strength of Zenpep as an authorized generic product. This product cannot be AB-rated to Zenpep because it is the identical product. (sam manufacturer, same production line).8,9,12
  • Pancrease MT and Pancreaze are identical products; however, the product packaging for Pancreaze complies with FDA requirements for reporting of enzyme contents.11,15
  • Ultresa and Ultrace MT are identical products; however, the product packaging for Ultresa complies with FDA requirements for reporting of enzyme contents17,19,24
  • Viokace and Viokase are identical products; however, the product packaging for Viokace complies with FDA requirements for reporting of enzyme contents. The new formulation Viokace tablets are not enteric coated and must be given concomitantly with a proton pump inhibitor (PPI) to ensure efficacy.18, 19, 22
  • All other marketed pancreatic enzyme replacement products are unapproved drugs, which are not AB-rated and may not be interchanged.18 Unapproved pancreatic enzyme replacement products may no longer be marketed.1-3,11,14

Safety

Use caution when switching patients between pancreatic enzyme replacement products and monitor patients closely after any change in therapy. No dosage recommendations are available for switching between products from different manufacturers and labeled enzyme contents may differ between FDA-approved products and unapproved products.25,26

Alternative Agents & Management

Switching Between Pancreatic Enzyme Products

  • Patients currently receiving therapy with pancreatic enzyme replacement products will need a new prescription when they switch to another product.23
  • There are no recommendations for switching patients between products from different manufacturers.
  • Clinicians may consider switching the patient to another product with a similar amount of enzymes, then adjusting the dose based on patient response. However, the labeled enzyme contents may differ between FDA-approved products and unapproved products, which may make it more difficult to switch between products.25,26
  • The labeled contents of FDA-approved products reflect the actual enzyme content of the product, while the labeled contents of unapproved products excludes overfill and underestimates the actual lipase content.1-4
  • The Table shows the recently available agents, along with any available equivalents.

Feeding Tube Administration

  • There are no approved pancreatic enzyme powders suitable for patient administration via feeding tubes.
  • Eurand has developed two procedures for administering Zenpep through enteral feeding tubes which are currently under review by FDA.27 Contact Eurand at 1-888-936-7371 for more detailed information.
    • The contents of Zenpep 5,000 lipase unit capsules may be mixed with applesauce at a ratio of 1 capsule per 5 mL applesauce and administered via gastrostomy tube (14 French or greater). Do not crush the contents of the Zenpep capsules.27
    • For patients with smaller gauge gastrostomy, nasogastric, or jejunal tubes, the contents of Zenpep capsules may be blended with enteral formula using a household blender. Any of the 4 Zenpep capsule strengths may be mixed with a commercial non-elemental enteral formula. Blend the enteric-coated beads from the Zenpep capsule with the enteral formula until no bead fragments are visible and use immediately following preparation. A dose of 2,000 lipase units per gram of fat is the recommended starting dose for Zenpep when mixed with enteral formulas.27,28
  • Some information is available regarding the administration of Creon through enteral feeding tubes in an unpublished in vitro study. The contents of 1 Creon Delayed Release Capsule were sprinkled onto 15 mL of acidic baby food (applesauce or bananas), gently stirred, and allowed to sit for 15 minutes. The mixture was then poured into a 35 mL syringe and administered into a gastric tube (size 18 French or larger), giving approximately 15 mL every 10 to 15 seconds. The tube was then flushed with 10 to 30 mL of water. The mixture retained more than 85% of lipase activity for 30 minutes after dissolution and did not clog or stick to the gastric tube. This procedure has not been evaluated in human clinical trials.29,30
  • Aptalis Pharma may have some information regarding administration of Viokace through enteral feeding tubes. Contact Aptalis Pharma at 1-800-472-2634 for details.
  • There is no data available regarding administration of any other FDA approved pancreatic enzyme product via enteral feeding tubes, including Pancreaze Delayed Release Capsules, Ultresa Delayed Release Capsules, or Pertzye Delayed-Release Capsules.19,21,29,31
Patients with Swallowing Difficulties
  • Creon may be used in patients who are unable to swallow an intact capsule. The contents of Creon capsules may be sprinkled on a small amount of acidic, soft food (eg, applesauce) immediately prior to ingestion. The patient should swallow the mixture without crushing or chewing the capsule contents, then follow the mixture with water or juice to ensure that the entire dose is ingested.27
  • Ultresa may be used in patients who are unable to swallow an intact capsule. The contents of Ultresa capsules may be sprinkled on a small amount of acidic, semisoft food (eg, applesauce, yogurt) immediately prior to ingestion. The patient should swallow the mixture without crushing or chewing the capsule contents, then follow the mixture with water or juice to ensure that the entire dose is ingested.17
  • Pertzye may be used in patients who are unable to swallow an intact capsule. The contents of Pertzye capsules may be sprinkled on a small amount of acidic, soft food (eg, applesauce) immediately prior to ingestion. The patient should swallow the mixture without crushing or chewing the capsule contents, then follow the mixture with water or juice to ensure that the entire dose is ingested.20
  • Aptalis Pharma may have information regarding administration of Viokace to patients with swallowing difficulties. Contact Aptalis Pharma at 1-800-472-2634 for details. 

Related Shortages

References

  1. Food and Drug Administration. FDA Guidance for Industry on Pancreatic Enzymes. Accessed January 22, 2010.
  2. Food and Drug Administration. Exocrine pancreatic insufficiency drug products; extension to obtain marketing approval. Federal Register. 2007;72(207):60860-60862. Accessed March 4, 2010. 
  3. Solvay Pharmaceuticals. Pancreatic Enzyme Information. Accessed March 11, 2010.
  4. Solvay Pharmaceuticals, Medical Information (written communication). Comparison between Creon formulations. July 2, 2009.
  5. Solvay Pharmaceuticals. Creon Frequently-Asked Questions. Accessed March 11, 2010.
  6. Creon Delayed-Release Capsules product information. North Chicago, IL: Abbott Laboratories; 2011 July.
  7. Solvay Pharmaceuticals, Customer Service (personal communication). May 11, 2010.
  8. X-Gen Pharmaceuticals. Pancrelipase Enzyme Products (PEP’s). Accessed March 11, 2010.
  9. Pancrelipase product information. Milan, Italy / Big Flats, NY: Eurand / X-Gen Pharmaceuticals. 2009 August.
  10. X-Gen Pharmaceuticals, Customer Service (personal communication). May 11, 2010.
  11. Ortho-McNeil-Janssen, Scientific Affairs (personal communication). April 15 and 29, May 11, and June 3 and 4, and July 15, 2010.
  12. Zenpep product information. Yardley, PA: Eurand Pharmaceuticals. 2011 July.
  13. Eurand Pharmaceuticals, Customer Service (personal communication). May 11, and June 3, 2010.
  14. Johnson & Johnson. FDA Approves New Drug Application for PANCREAZE™, press release. Accessed April 15, 2010.
  15. Pancreaze product information. Titusville, NJ: Ortho-McNeil-Janssen. 2010 April.
  16. Johnson & Johnson, Trade Relations (written communication). April 27, 2010.
  17. Ultresa Delayed-Release Capsules product information. Birmingham, AL: Aptalis Pharma; 2012 March.
  18. Viokace Tablets product information. Birmingham, AL: Aptalis Pharma; 2012 March.
  19. Aptalis Pharma, Customer Service (personal communications). March 2 and 5, April 24, July 6 and 9, September 18, and December 12, 2012.
  20. Pertzye Delayed-Release Capsules product information. Bethlehem, PA: Digestive Care; 2012 May.
  21. Digestive Care, Customer Service (personal communication). May 22, July 10, and September 18, 2012. 
  22. Food and Drug Administration. Updated Questions and Answers for Healthcare Professionals and the Public: Use an Approved Pancreatic Enzyme Product (PEP). Accessed May 22, 2012. 
  23. Food and Drug Administration. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Accessed March 11, 2010.
  24. Gannon S, Aptalis Pharma. Current Report to United States Securities and Exchange Commission. Form 8-K. Updated March 1, 2012. Accessed July 12, 2012.
  25. Murray L, ed. 2009 Red Book. Montvale, NJ: Thomson PDR; 2009.
  26. Wickersham RM, Novak KK, managing eds. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health, Inc.; 2009.
  27. Eurand Pharmaceuticals, Medical Affairs (written communication). August 16, 2010.
  28. Eurand Pharmaceuticals, Medical Affairs (personal communication). August 17, 2010.
  29. Abbott Pharmaceuticals, Medical Information (personal communications). August 17, 2010; and March 5, 2012.
  30. Shlieout, G, Koerner A, Maffert M, Forssmann K, Caras S. Administration of pancrelipase delayed-release pellets (Creon®) via gastrostomy tube is feasible with no loss of gastric resistance or lipase activity. Poster presented at: Digestive Disease Week; May 7-10, 2011; Chicago, IL. Poster Su1030. Available online. Accessed March 5, 2012.   
  31. Ortho-McNeil-Janssen, Scientific Affairs (personal communications). August 17, 2010; and March 5, 2012.
  32. Red Book Online. via Drugdex System [internet database]. Greenwood Village, CO: Thomson Healthcare; 2012.

Updated

Updated December 12, 2012 by M. Christina Beckwith, PharmD, Drug Information Specialist. Created March 11, 2010 by M. Christina Beckwith, PharmD, Drug Information Specialist. Copyright 2012, Drug Information Service, University of Utah, Salt Lake City, UT.

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