This set of Questions and Answers was originally posted on April 12, 2010, and updated on May 24, 2010, March 1, 2012 and May 17, 2012. It is being updated to provide additional information to healthcare professionals and the public about the safe use of approved pancreatic enzyme products.
Q1. What are pancreatic enzyme products?
Q2. Why has FDA been concerned about the PEPs that are not approved?
Q3. Which PEPs are approved by the FDA?
Q4. What is FDA doing to ensure that the public is aware of the changes in PEP availability?
Q5. For patients who need a PEP, but cannot take one by mouth, are any of the PEPs approved for use in a gastrostomy tube (G-tube)?
Q6. What are the key points patients need to know about PEPs?
Q7. What are the key points for healthcare professionals to know about PEPs?
A. Pancreatic enzyme products (PEPs) contain the active ingredient pancrelipase, a mixture of the digestive enzymes amylase, lipase, and protease. These digestive enzymes are used to improve food digestion in patients whose bodies do not produce enough pancreatic enzymes. PEPs have been used to treat patients with various pancreatic disorders, including cystic fibrosis, Shwachman-Diamond syndrome, chronic pancreatitis, pancreatic tumors, or removal of all or a part of the pancreas. Although PEPs have been used for several decades, they have been marketed in the U.S. as unapproved products.
A. Several years ago, FDA became aware that unapproved PEPs contained variable amounts of the therapeutic enzymes (lipase, amylase, and protease), which were causing patients to notice changes in their ability to digest food due to under-dosing, or adverse events due to overdosing. An important characteristic of the drug approval process is that companies must demonstrate they are able to manufacture their products with sufficient consistency and quality to ensure patients do not experience problems due to dose variation.
In July 1991, FDA announced that all PEPs must be approved, and that any company that wished to newly market or continue to market a PEP would have to submit a New Drug Application (NDA). This was done to assure the safety, effectiveness, and product quality for the PEPs. Some companies began the application process soon after this announcement. In 2004, FDA notified PEP manufacturers of its intent to permit marketing of unapproved products while the companies worked on their applications. However, FDA required approval of all marketed PEPs by April 28, 2008.
In 2006, FDA issued a guidance that described the requirements manufacturers would have to meet to ensure that a PEP product was effective, safe and of sufficient quality for FDA approval. In 2007, because of the difficulties encountered in manufacturing these products, FDA extended the deadline for approval to April 28, 2010.
Despite FDA's technical assistance to all manufacturers of PEPs and extension of the approval deadline, some of the products did not receive FDA approval for marketing prior to the April 28, 2010 deadline.
The FDA found quality problems with the unapproved PEPs and has worked intensively with the manufacturers of these products towards approval.
A. As of May 17, 2012, FDA has approved six PEPs because they meet the regulatory standards for quality, safety, and effectiveness. Creon and Zenpep were approved for marketing in 2009, Pancreaze was approved in April 2010, Ultresa and Viokace were approved in March 2012 and Pertzye was approved May 17, 2012. All approved PEP products have drug labels with important information for healthcare professionals and Medication Guides for patients that explain the product's risks and benefits.
A. The agency continues to work with patient advocacy groups and healthcare professional organizations to help ensure the public is aware of the six approved products and changes in PEP availability.
Q5. For patients who need a PEP, but cannot take one by mouth, are any of the PEPs approved for use in a gastrostomy tube (G tube)?
A. FDA is aware that some patients may not be able to take PEPs by mouth. Although PEPs are not approved for administration via gastrostomy tubes, a small number of patients may require PEPs to be given through this route. Manufacturers of approved PEPs are currently conducting tests to evaluate the feasibility of administering PEPs via gastrostomy tubes. FDA is committed to assuring that recommendations for gastrostomy tube administration techniques become available in the near future for all patients requiring use of these approved products.
A. FDA recommends that patients:
- Know that Creon, Zenpep, Pancreaze, Ultresa, Viokace, and Pertzye are currently the only FDA-approved PEPs sold in the United States.
- Know that Creon, Zenpep, Pancreaze, Ultresa, and Pertzye are used to treat people who cannot digest food normally because their pancreas does not make enough pancreatic enzymes due to cystic fibrosis or other conditions.
- Know that Creon, Zenpep, Pancreaze, Ultresa, and Pertzye have a special coating on the drug, known as enteric coating, that helps prevent the drug from breaking down in the stomach, and delays the release of the drug until it reaches the lower digestive tract.
- Know that Viokace is the only PEP without an enteric coating. Viokace must be taken with a drug known as a proton pump inhibitor (PPI). The PPI decreases stomach acid to help prevent the drug from breaking down in the stomach, and delays the release of the drug until it reaches the lower digestive tract.
- Know that Viokace, taken with a PPI, is used to treat adults who cannot digest food normally. Adults with swelling of the pancreas that lasts a long time (chronic pancreatitis), or who have had some or all of their pancreas removed (pancreatectomy) may not digest food normally because they do not make enough enzymes or because their enzymes are not released into the bowel (intestine).
- Recognize that it may take 1-2 weeks to adjust the dose of the new PEP.
- Take their PEP as prescribed.
- Read the Medication Guide given with each prescription of an FDA-approved PEP. The Medication Guide is written for patients to help them understand the benefits and risks of using PEPs.
- Talk with their healthcare professional about any concerns they have about PEPs.
A. FDA recommends that healthcare professionals:
- Be aware that Creon, Zenpep, Pancreaze, Ultresa, Viokace, and Pertzye are currently the only FDA-approved PEPs that are marketed in the United States.
- Be aware that PEPs are not interchangeable at the pharmacy. Patients currently taking an unapproved PEP will require a new prescription for Creon, Zenpep, Pancreaze, Ultresa, Viokace, or Pertzye.
- Be aware that the approved PEPs are different from their unapproved versions because changes were made in their formulations to meet FDA's standards for safety, effectiveness, and product quality.
- Be aware that Creon, Zenpep, Pancreaze, Ultresa, and Pertzye are indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions.
- Be aware that Creon, Zenpep, Pancreaze, Ultresa, and Pertzye are enteric coated to help prevent the drug from breaking down in the stomach, and delay the release of the drug until it reaches the lower gastrointestinal tract.
- Be aware that Viokace is the only non-enteric coated pancrelipase product. Viokace must be taken in combination with a PPI to help prevent the drug from breaking down in the stomach, and delay the release of the drug until it reaches the lower gastrointestinal tract.
- Be aware that Viokace, in combination with a proton pump inhibitor (PPI), is indicated in adults for the treatment of exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatectomy.
- When switching a patient to another PEP, consider starting with a similar amount of lipase enzyme, then adjust the dose based on the patient's response.
- Recognize that the labeled contents of FDA-approved PEPs reflect the actual enzyme content of the product, whereas the labeled contents of unapproved PEPs underestimate the actual lipase content.
- Recognize that it may take 1-2 weeks for a patient to adjust their dose of the new PEP. Individual patient response should be monitored when switching from an unapproved PEP to an approved one.
- Follow the dosing recommendations in the labeling for the FDA-approved PEPs.
- Instruct patients and caregivers that PEPs should only be taken as directed.
- Although PEPs are not approved for administration via gastrostomy tubes, a small number of patients may require PEPs to be given through this route. Manufacturers of approved PEPs are conducting tests to evaluate the feasibility of administering PEPs via gastrostomy tubes, and FDA is committed to assuring that data-driven recommendations are available to guide the use for all patients requiring use of these approved products.
Pancrelipase (marketed as Pancreaze, Creon and Zenpep) Information Exocrine Pancreatic Insufficiency Drug Products; Extension to Obtain Marketing Approval
October 2007 Federal Register Notice
Exocrine Pancreatic Insufficiency Drug Products; Draft Guidance for Submitting New Drug Applications; Notices
April 2004 Federal Register Notice