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Drugs and Health Products

Monograph: Pancreatic Enzymes

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This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLAs) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient.

Notes

  • The term "pancreatic enzymes" is used as a collective term for various enzyme preparations derived from animal pancreas. For pharmacopoeial grade ingredients, the applicant must use the proper name and common name as provided in the pharmocopoeia.
  • To ensure consistent representation of enzyme-containing products, pancreatic enzyme activity must be expressed in USP units in the PLA and label.
  • Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant’s discretion.
  • The solidus (/) indicates that the terms and/or the statements are synonymous. Either term or statement may be selected by the applicant.

Date

February 13, 2014

Proper name(s)

Pancreatic enzymes (US FDA 2010; WHO 2011)

Common name(s)

Pancreatic enzymes (US FDA 2010; WHO 2011)

Source material(s)

  • Bovine (Bos taurus (Bovidae)) pancreas (BP 2012; Ph.Eur. 2012; USP 35; Bisby et al. 2011)
  • Porcine (Sus scrofa (Suidae)) pancreas (BP 2012; Ph.Eur. 2012; USP 35; Bisby et al. 2011)

Route(s) of administration

Oral

Dosage form(s)

  • The only acceptable pharmaceutical dosage forms are delayed-release capsules, tablets, or granules (e.g. enteric-coated tablets, capsules containing enteric-coated granules/(mini)microspheres) (Friess et al. 1999; Suarez et al. 1999; Sharpé et al. 1997).
  • The dosage form must be qualified with an additional term to describe the delayed release (e.g. enteric-coated capsules, gastro-resistant tablets, microencapsulated pancreatic enzymes) (WHO 2011).
  • This monograph standard is not intended to include foods or food-like dosage forms such as bars, chewing gums or beverages.

Use(s) or Purpose(s)

Statement(s) to the effect of:

  • Digestive aid (Cichoke 2006).
  • Digestive aid to help decrease bloating after high caloric, high fat meals (Suarez et al. 1999).
  • Digestive enzyme (Cichoke 2006).
  • Helps to decrease bloating after high caloric, high fat meals (Suarez et al. 1999).

Dose(s)

Subpopulation(s)

Adults (≥ 18 years)

Quantity(ies)

Dose information must include the quantities of both the enzyme preparation and its enzymatic activity:

  • Enzyme preparation (lipase, amylase, and protease) per dosage unit; and
  • Enzyme activity providing all the following, one to four times per day (USP 35; Suarez et al. 1999; Domínguez-Muñoz et al. 1997):
    • amylase: 1.7 x 104 – 1.49 x 105 amylase units per day, not to exceed 3.7 x 104USP units per single dose
    • lipase: 5.0 x 103 – 4.0 x 104 USP lipase units per day, not to exceed 2.0 x 104USP units per single dose
    • protease: 1.6 x 104 – 1.25 x 105USP protease units per day, not to exceed 3.8 x 104USP units per single dose

Note:
Pharmacopoeial units other than USP may be represented on the label as additional information. The following approximate conversion factors can be used to convert the activities of pancreatic enzymes into USP units (Scharpé et al. 1997):
For amylase: 1 Ph.Eur. Unit = 1 BP Unit = 1 FIP Unit ~ 4.15 USP Units
For lipase: 1 Ph.Eur. Unit = 1 BP Unit = 1 FIP Unit ~ 1 USP Unit
For protease: 1 Ph.Eur. Unit = 1 BP Unit = 1 FIP Unit ~ 62.5 USP Units

Directions for use

All products:

  • Use the smallest effective dose which controls symptoms (CPS 2008; Sharpé et al. 1997).
  • Take with or immediately before a meal/food (Ferrone et al. 2007; Suarez et al. 1999; Friess et al. 1998; Domínguez-Muñoz et al. 1997).

Enteric-coated products:
Swallow whole/do not crush or chew (CPS 2008).

Capsule products containing (mini)microspheres and delayed-release granules:
(For individuals who experience difficulties swallowing capsules, the capsules may be opened and) the granules/(mini)microspheres may be mixed with soft food or fluid. Use immediately after mixing (Martindale 2011; CPS 2008).

Duration of use

Consult a health care practitioner for use beyond four weeks (Friess et al. 1998).

Risk information

Statement(s) to the effect of:

Caution(s) and warning(s)

  • If symptoms persist or worsen, consult a health care practitioner.
  • If you are pregnant or breastfeeding, consult a health care practitioner prior to use.
  • If you have diabetes, consult a health care practitioner prior to use.
  • If you have pancreatitis, pancreatic exocrine insufficiency or cystic fibrosis, consult a health care practitioner prior to use (Halm et al. 1999; Delhaye et al. 1996; Guarner et al. 1993).

Contraindication(s)

All products:
If you are sensitive to pancreatic enzymes, do not use this product (Martindale 2011; CPS 2008).

Products from hog/pig pancreas:
If you are sensitive to pork proteins, do not use this product (Martindale 2011; CPS 2008).

Known adverse reaction(s)

Nausea, vomiting, abdominal pain/epigastric pain and/or heartburn have been known to occur, in which case discontinue use (and consult a health care practitioner) (Friess et al. 1998).

Non-medicinal ingredients

Must be chosen from the current NNHPD Natural Health Products Ingredients Database and must meet the limitations outlined in the database.

Storage conditions

Statement(s) to the effect of:

Store in a tightly closed, light-resistant container in a cool, dry place (BP 2012; Ph.Eur. 2012; USP 35).

Specifications

  • The finished product specifications must be established in accordance with the requirements described in the NNHPD Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredients Database (NHPID).
  • The specifications must include testing for enzymatic activity of the medicinal ingredient at appropriate stages of formulation and manufacturing using the assay outlined in the current United States Pharmacopeia (USP):
    Pancrelipase – assay for amylase, lipase and protease activity.
  • The medicinal ingredient may comply with the pancreatic enzyme preparation specifications outlined in the current British, European and United States pharmacopoeial monographs:
    BP: Pancreatin; Pancreatic extract; Pancreas Powder
    Ph.Eur.: Pancreas powder / Pancreatis pulvis
    USP: Pancrelipase
  • Overages to compensate for the loss of activity during manufacturing and shelf-life of the finished product are permitted as per the pharmacopoeial standard.
  • Where published methods are not suitable for use, manufacturers will use due diligence to ensure that the enzymes remain active to the end of the shelf life indicated on the product label.

References cited

  • Bisby FA, Roskov YR, Orrell TM, Nicolson D, Paglinawan LE, Bailly N, Kirk PM, Bourgoin T, Baillargeon G, Ouvrard D, editors.Next link will take you to another Web site Species 2000 & ITIS Catalogue of Life, 15th March 2012 [Internet]. Reading (GB): Species 2000. [Source database: ITIS: The Integrated Taxonomic Information System, Version Apr 2011; Accessed 2012 March 16].
  • BP 2012: British Pharmacopoeia 2012. Volume II. London (GB): The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA); 2012.
  • Cichoke AJ. Pancreatic Enzymes. In: Pizzorno JE, Murray MT, editors. Textbook of Natural Medicine, Third edition, volume 1. St. Louis (MI): Churchill Livingstone Elsevier; 2006. p. 1131-1146.
  • CPS 2008: Compendium of Pharmaceuticals and Specialties: The Canadian Drug Reference for Health Professionals. Ottawa (ON): Canadian Pharmacists Association; 2008.
  • Delhaye M, Meuris S, Gohimont AC, Buedts K, Cremer M. Comparative evaluation of a high lipase pancreatic enzyme preparation and a standard pancreatic supplement for treating exocrine pancreatic insufficiency in chronic pancreatitis. European Journal of Gastroenterology and Hepatology 1996;8:699-703.
  • Domínguez-Muñoz JE, Birckelbach U, Glasbrenner B, Sauerbruch T, Malfertheiner P. Effect of oral pancreatic enzyme administration on digestive function in healthy subjects: comparison between two enzyme preparations. Alimentary Pharmacology and Therapeutics 1997;11(2):403-408.
  • Ferrone M, Raimondo M, Scolapio JS. Pancreatic enzyme pharmacotherapy. Pharmacotherapy 2007;27(6):910-920.
  • Friess H, Kleeff J, Malfertheiner P, Müller MW, Homuth K, Büchler MW. Influence of high-dose pancreatic enzyme treatment on pancreatic function in healthy volunteers. International Journal of Pancreatology 1998;23(2):115-123.
  • Guarner L, Rodríguez R, Guarner F, Malagelada JR. Fate of oral enzymes in pancreatic insufficiency. Gut 1993;34:708-712.
  • Halm U, Löser C, Löhr M, Katschinski M, Mössner J. A double-blind, randomized, multicentre, crossover study to prove equivalence of pancreatin minimicrospheres versus microspheres in exocrine pancreatic insufficiency. Alimentary Pharmacology and Therapeutics 1999;13(7):951-957.
  • Martindale 2011:Sweetman SC, editor.Next link will take you to another Web site Martindale: The Complete Drug Reference [Internet]. London (GB): Pharmaceutical Press; 2011. [Pancreatic enzymes: latest modification 09-Apr-2011; Accessed 2012 March 16].
  • Ph.Eur. 2012: European Pharmacopoeia. 7th edition. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM), 2012.
  • Scharpé S, Uyttenbroeck W, Samyn N. Pancreatic Enzyme Replacement. In: Lauwers A, Scharpé S, editors. Pharmaceutical Enzymes. London (GB): Taylor & Francis, Inc; 1997. p. 187-221.
  • Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Digestive Diseases and Sciences 1999;44(7):1317-1321.
  • US FDA 2010:Next link will take you to another Web site Postmarket Drug Safety Information for Patients and Providers. Updated Questions and Answers for Healthcare Professionals and the Public: Use an Approved Pancreatic Enzyme Product (PEP), Page last updated: 05/24/2010. [Internet] [Accessed 2012 March 16].
  • USP 35: United States Pharmacopeia and the National Formulary (USP 35 - NF 30). Rockville (MD): The United States Pharmacopeial Convention; 2012.
  • WHO 2011:Next link will take you to another Web site WHO Model List of Essential Medicines, 17th edition, March 2011 [Internet]. [Accessed 2012 March 16].

References reviewed