What is a Good Substitute for CREON? Exploring Pancreatic Enzyme Alternatives

October 11, 2025 •

4 min read

More than 50% of pancreatic enzyme replacement therapy (PERT) prescriptions in the US are for CREON. For patients with exocrine pancreatic insufficiency (EPI), understanding what is a good substitute for CREON is essential due to varying costs, insurance coverage, or tolerability.

Quick Summary

Explore prescription and over-the-counter alternatives for CREON, including FDA-approved options like Zenpep, Pancreaze, Pertzye, and Viokace, for managing pancreatic enzyme insufficiency.

Key Points

Prescription Alternatives: FDA-approved prescription substitutes for CREON include Zenpep, Pancreaze, Pertzye, and Viokace, all containing the enzyme mixture pancrelipase.
Not Interchangeable at the Pharmacy: Different pancrelipase brands have unique formulations and release mechanisms, meaning they are not interchangeable and require a doctor's guidance to adjust dosage safely.
Over-the-Counter Supplements: OTC fungal-based or porcine-based enzyme supplements are not FDA-regulated for efficacy and consistency and are not a reliable replacement for prescription PERT.
Viokace Requires a PPI: Viokace is an uncoated tablet formulation that must be taken with a proton pump inhibitor to prevent the enzymes from being destroyed by stomach acid.
Consider Cost and Coverage: Insurance coverage varies for different pancrelipase brands, so checking your plan and exploring manufacturer assistance programs can be crucial for affordability.

Understanding Pancreatic Enzyme Replacement Therapy (PERT)

Pancreatic Enzyme Replacement Therapy (PERT) is a crucial treatment for individuals with exocrine pancreatic insufficiency (EPI), a condition where the pancreas does not produce enough of the digestive enzymes (lipase, protease, and amylase) needed to break down food. This can result from conditions such as cystic fibrosis, chronic pancreatitis, or pancreatic cancer. CREON is one of the most widely known brand names for pancrelipase, the mixture of these enzymes. However, patients may need to consider alternatives due to factors like cost, insurance coverage, tolerability, or dietary preferences.

FDA-Approved Prescription Alternatives to CREON

All FDA-approved pancreatic enzyme products (PEPs) contain pancrelipase derived from porcine (pig) pancreatic glands, though their specific formulations and delivery mechanisms differ. This means they are not interchangeable at the pharmacy and a doctor's guidance is necessary when switching.

Zenpep (Pancrelipase)

Zenpep is a common alternative to CREON and has been shown in clinical studies to be comparable in efficacy. Both drugs are enteric-coated capsules designed to protect the enzymes from stomach acid until they reach the small intestine. While the active ingredients are the same, the specific manufacturing and coating can affect absorption and tolerability for some patients. Zenpep offers a comprehensive range of dosage options and is approved for use in both adults and pediatric patients.

Pancreaze (Pancrelipase)

Like Zenpep, Pancreaze is another porcine-based, enteric-coated capsule formulation of pancrelipase. It is also FDA-approved for treating EPI in both adult and pediatric populations. Some patients may find Pancreaze to be more affordable, depending on their insurance plan and available patient assistance programs.

Pertzye (Pancrelipase)

Pertzye is another FDA-approved pancrelipase product. One distinguishing feature is that its package insert contains specific information for administration via a gastrostomy (G)-tube, which may be a critical factor for certain patients. It is available in different strengths to meet varying dosage needs.

Viokace (Pancrelipase)

Viokace stands apart from the others because it is an uncoated tablet formulation. Because of this, it must be taken in combination with a proton pump inhibitor (PPI) to protect the enzymes from being degraded by stomach acid. This may be a suitable option for patients who experience issues with the dissolution of enteric-coated capsules. Viokace is indicated for use in adults with EPI caused by chronic pancreatitis or pancreatectomy.

Over-the-Counter (OTC) and Dietary Options: A Cautious Approach

For those seeking alternatives outside of prescription medications, OTC options exist, but they come with significant caveats. Neither OTC animal-based nor fungal-based enzyme supplements are regulated with the same rigor as FDA-approved medications.

OTC Animal-Based Enzymes: These may not be enteric-coated, which is crucial for protecting enzymes from stomach acid and delivering them effectively to the small intestine. As a result, they may be less effective and require a higher dose to achieve a similar result as a prescription product.
Fungal-Based Enzymes: Made from fungi, these are an option for individuals who wish to avoid animal products. However, there are no FDA-approved prescription fungal enzymes, and OTC versions are not subject to the same quality standards.
Dietary Supplements: Natural supplements like ginger and turmeric may help with some gastrointestinal symptoms, but they are not a substitute for prescription pancreatic enzyme formulations for people with true EPI.

Key Factors When Considering a CREON Substitute

When discussing a switch with your healthcare provider, several factors should be weighed:

Insurance Coverage and Cost: The cost of PERT can vary greatly based on your insurance plan and whether it covers a specific brand. Checking with your provider about coverage and exploring manufacturer assistance programs is essential.
Tolerability: Minor differences in formulation can affect how a patient tolerates a medication. While many patients tolerate different brands similarly, some may find that one brand causes fewer side effects.
Specific Needs: Some patients may require the tablet form of Viokace, while others may need G-tube administration and find Pertzye or specific handling instructions for CREON or Viokace useful.

Comparison of Pancrelipase Products


Feature	CREON	Zenpep	Pancreaze	Viokace	OTC Enzymes (Fungal/Porcine)
Formulation	Enteric-coated capsule	Enteric-coated capsule	Enteric-coated capsule	Uncoated tablet	Variable (often not enteric-coated)
Need for PPI?	No	No	No	Yes	No
Source	Porcine	Porcine	Porcine	Porcine	Fungal or Porcine
FDA-Approved?	Yes	Yes	Yes	Yes	No
Pediatric Use	Yes	Yes (1+ year)	Yes	No	Varies (not FDA approved)

How to Switch Safely Under a Doctor's Guidance

Switching between pancrelipase products is not a simple one-to-one exchange. Due to differences in formulation, release mechanisms, and enzyme concentrations, a healthcare provider must guide the transition. The new dosage may need to be adjusted over one to two weeks, and patient response should be closely monitored. Never attempt to switch your medication without medical supervision.

Conclusion

While CREON is a widely used and effective pancreatic enzyme replacement, several viable prescription alternatives are available for patients with EPI. FDA-approved options like Zenpep, Pancreaze, Pertzye, and Viokace offer similar benefits with distinct formulations that may suit different patient needs, tolerability profiles, or insurance plans. Over-the-counter enzymes exist but lack the rigorous FDA regulation and quality control of prescription products, making them an unreliable substitute. The most critical step is to consult your doctor to find the most effective and appropriate alternative for your specific situation. For more information on pancreatic enzymes, financial support resources, or related topics, consult the Pancreatic Cancer Action Network (PanCAN).

Summary of Prescribed and OTC Options

Prescription Alternatives: Zenpep, Pancreaze, Pertzye, and Viokace are FDA-approved pancrelipase products.
OTC Options: Fungal-based or porcine-based supplements are available but are not FDA-regulated and may be less effective.
Viokace Specifics: Viokace is an uncoated tablet that requires co-administration with a PPI.
Non-Interchangeable: Pancrelipase products are not interchangeable at the pharmacy; dosage must be re-evaluated and adjusted by a healthcare provider.
Factors to Consider: Cost, insurance coverage, tolerability, and the specific delivery mechanism (capsule vs. tablet) are all important factors when switching.
Important Note: Dietary changes and natural remedies are not a substitute for prescription PERT.

Frequently Asked Questions

Patients might switch from CREON due to issues with cost, insurance coverage limitations, intolerability or side effects, or a preference for a non-porcine-based product, although all prescription options are porcine-derived.

There is currently no FDA-approved generic version of CREON (pancrelipase) available on the market. All prescription pancrelipase products are brand-name.

No. While they contain the same active enzymes, their specific formulations, coatings, and concentrations differ, which is why they are not considered interchangeable without a doctor's guidance.

It is not recommended to use OTC supplements as a replacement for prescription pancreatic enzymes. They are not FDA-regulated for efficacy and consistency and are typically less effective because they are often not enteric-coated.

Both Zenpep and CREON are enteric-coated pancrelipase capsules with similar efficacy. The main differences are in their dosage options, cost based on insurance coverage, and specific formulation, which can affect patient tolerability.

Viokace is an uncoated tablet, so it needs a PPI to reduce stomach acid, which protects the enzymes from being destroyed before they can reach the small intestine and become active.

Common side effects, including stomach pain, bloating, or diarrhea, are often mild and can occur with any pancrelipase product. They may indicate the need for a dosage adjustment, which should be done under a doctor's supervision.

If your insurance stops covering CREON, you should talk to your doctor and pharmacist. They can help you explore covered alternatives like Zenpep or Pancreaze and discuss appealing the insurance company's decision or using manufacturer assistance programs.