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Drugs and Health Products

Monograph: Papain

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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: (i) Text in parentheses is additional optional information which can be included on the PLA and product label at the applicant's discretion. (ii) The solidus (/) indicates that the terms and/or the statements are synonymous. Either term or statement may be selected by the applicant.

Date: 2012-07-10

NHPID Name

Papain (IUBMB 2007)

Proper Name(s)

Papain ( IUBMB 2000 )

Common Name(s)

Papain ( IUBMB 2000 )

Source Material


Route Of Administration

Oral

Dosage Form(s)

  • The acceptable pharmaceutical dosage forms include, but are not limited to capsules, chewables (e.g. gummies, tablets), liquids, powders, strips or tablets.
  • This monograph 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 enzyme  (Merck 2012)

Dose(s)

Adults:

Dose(s):
not to exceed 1200 Milligrams per day of enzyme preparation of latex from papaya leaf and/or unripe fruit , not to exceed 400 Milligrams per single dose
 (Dorr and Herrmann 2007, Martin et al. 2002, Dale et al. 2001, Morton 1987)

Directions For Use: Take with food/meal

Dose(s):
not to exceed 7200000 FCC papain units per day , not to exceed 2400000 FCC papain units per single dose
 (Martin et al. 2002, Dale et al. 2001)

Directions For Use: Take with food/meal


  • Dose unit information must include the quantities of both the enzyme preparation (mg or ml) and its enzymatic activity (FCC or USP units). When submitting by ePLA, please put the enzymatic activity quantity in the Quantity/Unit fields (field 77) and the quantity of enzyme preparation in mg or ml in the Additional Quantity/Unit fields.
  • For multi-ingredient products containing both papain and bromelain (fruit and/or stem), the combined proteolytic activity should not exceed the maximum proteolytic activity of 130 000 000 FCC PU per day.
  • One FCC papain unit is approximately equivalent to one USP papain unit (1 FCC PU approx. 1 USP PU).
  • One papain unit (PU) is defined as that quantity of enzyme that liberates the equivalent of 1 microgram of tyrosine per hour under the conditions of the assay (FCC 8).

Duration of use

For prolonged use, consult a health care practitioner.

Risk Information

Statement(s) to the effect of:

Caution(s) and Warning(s):
  • If you are pregnant or breastfeeding, consult a health care practitioner prior to use
  • If you have a gastrointestinal lesion/ulcer, are taking an anticoagulant/ blood thinner or an anti-inflammatory, or are having surgery, consult a health care practitioner prior to use.  (Martindale 2011)
  • If you have allergy to latex or fruits (such as avocado, banana, chestnut, passion fruit, fig, melon, mango, kiwi, pineapple, peach, and tomato), consult a health care practitioner prior to use  (US FDA 2008, APhA 2006, Brehler et al. 1997)

Contraindication(s):
No statement is required

Known Adverse Reaction(s):
Hypersensitivity/allergy has been known to occur; in which case, discontinue use  (HC 2011, Martindale 2011, US FDA 2008)

Non-medicinal ingredients

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

Specifications

  • The finished product specifications must be established in accordance with the requirements described in the NHPD Quality of Natural Health Products Guide.
  • The medicinal ingredient must comply with the requirements outlined in the Natural Health Products Ingredient Database (NHPID).
  • Details of the manufacturing of the enzyme at the raw material stage should include fermentation medium and the isolation process of the medicinal ingredient.
  • The medicinal ingredient may comply with the specifications outlined in the current United States Pharmacopeia (USP): Papain.
  • 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 Food Chemicals Codex (FCC): PLANT PROTEOLYTIC ACTIVITY.
  • Where published methods are not suitable for use, manufacturers will use due diligence to ensure that the enzymes remain active to the end of their shelf life indicated on the product label.

References cited

  • APhA 2006: Berardi RR, Kroon LA, McDermott JH, Newton GD, Oszko MA, Popovich NG, Remington TL, Rollins CJ, Shimp LA, Tietze KJ, editors. Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care, 15th edition. Washington (DC): APhA Publications; 2006.
  • Brehler R, Theissen U, Mohr C, Luger T. 1997. ''Latex-fruit syndrome'': frequency of cross-reacting IgE antibodies. Allergy 52(4):404-410.
  • Dale PS, Tamhankar CP, George D, Daftary GV. Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects. Cancer Chemotherapy and Pharmacology 2001;47(Suppl):S29-S34.
  • Dörr W, Herrmann T. Efficacy of Wobe-Mugos® E for reduction of oral mucositis after radiotherapy. Strahlentherapie und Onkologie 2007;183:121-127.
  • FCC 8: Food Chemicals Codex, Eighth edition. Rockville (MD): The United States Pharmacopeial Convention; 2012.
  • HC 2011: Canada Vigilance Adverse Reaction Online Database. Search Criteria: Papain. [Accessed 2012 March 16]. Available from: http://www.hc-sc.gc.ca/dhp-mps/medeff/databasdon/index-eng.php
  • IUBMB 2000: Nomenclature Committee of the International Union of Biochemistry and Molecular Biology. [Internet]. London (GB): Queen Mary, University of London [papain: CAS 9001-73-4, EC 3.4.22.2 created 1961 as EC 3.4.4.10, transferred 1972 to EC 3.4.22.2, modified 1976, modified 2000; Accessed 2012 March 16]. Available from: http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/4/22/2.html
  • Martin T, Uhder K, Kurek R, Roeddiger S, Schneider L, Vogt HG, Heyd R, Zamboglou N. Does prophylactic treatment with proteolytic enzymes reduce acute toxicity of adjuvant pelvic irradiation? Results of a double-blind randomized trial. Radiotherapy and Oncology 2002;65:17-22.
  • Martindale 2011: Sweetman SC, editor. 2011. Martindale: The Complete Drug Reference. [Internet]. London (GB): Pharmaceutical Press. [Papain: CAS 9001-73-4, syn: EC 3.4.22.2, latest modification: 10-Oct-2011; Accessed 2012 July 9]. Available from: http://www.medicinescomplete.com
  • Merck 2012: The Merck Index Version 14.1 [Internet]. Whitehouse Station (NJ): Merck & Co., Inc. [Published 2006; Updated 2012; Accessed 2012 July 10]. Available from: http://www.medicinescomplete.com/mc/merck/current/monographs.htm
  • Morton J. 1987. Papaya. In: Morton JF. Fruits of Warm Climates. Miami (FL): Julia F. Morton; p. 336-346. [Accessed 2012 March 16]. Available from: http://www.hort.purdue.edu/newcrop/morton/papaya_ars.html
  • US FDA 2008: Topical Drug Products Containing Papain; Enforcement Action Dates. Department of Health and Human Services. Docket No. FDA-2008-N-0481.
  • USDA 2011: United States Department of Agriculture, Agricultural Research Service, National Genetic Resources Program. Germplasm Resources Information Network (GRIN) [online database]. Beltsville (MD): National Germplasm Resources Laboratory. [Carica papaya L. (Caricaceae): Last updated 09-May-2011; Accessed 2012 March 16]. Available from: http://www.ars-grin.gov/cgi-bin/npgs/html/tax_search.pl
  • USP 35: United States Pharmacopeia and the National Formulary (USP 35 - NF 30). Rockville (MD): The United States Pharmacopeial Convention; 2012.

References reviewed

  • Evidence for Quality of Finished Natural Health Products, Version 2.0 [Internet]. Ottawa (ON): Natural Health Products Directorate, Health Canada. 2007. [Accessed 2012 March 28]. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/legislation/docs/eq-paq-eng.php
  • Repchinsky C, editor-in-chief. Patient Self-Care: Helping Patients Make Therapeutic Choices, 1st edition. Ottawa (ON): Canadian Pharmacists Association; 2002.