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Drugs and Health Products

Monograph: Pseudoephedrine for children 6-12 years

COMPLIANCE WITH PRECURSOR CONTROL REGULATIONS: The Precursor Control Regulations (PCR) (JC 2010a) allows Canada to fulfill its international obligations with respect to the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988, and provides a framework for the regulation of activities involving precursor chemicals which can be used in the production of illicit drugs and substances. Under the PCR, regulated chemicals are grouped into two classes: Class A and Class B. For class A precursors such as pseudoephedrine and/or products containing them, persons wishing to be involved in activities such as importation, exportation, production, packaging, selling, and/or providing must first obtain a licence. Further information regarding compliance with the PCR, including application forms and guidance documents pertaining to the application for a Class A precursor licence, is available at: http://www.healthcanada.gc.ca/precursors.

Date: 2010-06-09

NHPID Name

Pseudoephedrine (O'Neil et al. 2012)

Proper Name(s)

Common Name(s)

Pseudoephedrine ( NLM 2009 , O'Neil et al. 2009 )

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:

Dose(s)

Children 6 - 12 years:

Dose(s):
30 - 120 Milligrams per day , not to exceed 30 Milligrams per single dose
 (Simons et al. 1996, Dickerson et al. 1978)

Directions For Use:
  • Do not give with any other cough and cold medications since harm may occur (HC 2009)
  • Take every 4-6 hours


See Appendices 1 and 2 for dosage information.

Duration of use

Consult a health care practitioner for use beyond 7 days.  (HC 2009, US FDA 2004)

Risk Information

Statement(s) to the effect of:

Caution(s) and Warning(s):

Contraindication(s):
No statement is required

Known Adverse Reaction(s):
  • Allergic reactions, breathing difficulties, convulsions, drowsiness, hallucinations, and rapid heart rate have been known to occur; in which case, discontinue use.  (HC 2009, Blumenthal et al. 2000)
  • Rapid heartbeat has been known to occur; in which case, discontinue use.  (Dickerson et al. 1978)

Non-medicinal ingredients

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

Storage Conditions

Store protected from light and moisture (BP 2009, USP 32, Ph. Eur. 2007).

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).
  • The medicinal ingredient may comply with the specifications outlined in the following monographs: (i) Pseudoephedrine Hydrochloride published in the European Pharmacopoeia (Ph. Eur. 2007) and (ii) Pseudoephedrine Hydrochloride and Pseudoephedrine Sulfate monographs published in the U.S. Pharmacopeia (USP 32).

References cited

  • Bensky D, Clavey S, Stoger E. Gamble A. 2004. Chinese Herbal Medicine: Materia Medica, 3RD Edition. Seattle (WA): Eastland Press.
  • Blumenthal M, Goldberg A, Brinkmann J, editors. 2000. Herbal Medicine: Expanded Commission E Monographs. Boston (MA): Integrative Medicine Communications.
  • BP 2009: British Pharmacopoeia Commission. 2009. British Pharmacopoeia, 2009, Volume 1. London (GB): The Stationary Office on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA).
  • Bright TP, Sandage Jr BW, Fletcher HP. 1981. Selected cardiac and metabolic responses to pseudoephedrine with exercise. The Journal of Clinical Pharmacology 21:488-492.
  • Brinker F. 2001. Herb Contraindications and Drug Interactions, Third Edition. Sandy (OR): Eclectic Medical Publications.
  • Brinker F. 2008. Online Updates and Additions to Herb Contraindications and Drug Interactions, 3rd edition. Sandy (OR): Eclectic Medical Publications. [Accessed 2009 November 20]. Available from: http://www.eclecticherb.com/emp/updatesHCDI.html
  • Bye CE, Cooper J, Empey DW, Fowle ASE, Hughes DTD, Letley E, O'Grady J. 1980. Effects of pseudoephedrine and tripolidine, alone and in combination, on symptoms of the common cold. British Medical Journal 281(6234):189-190.
  • Dickerson J, Perrier D, Mayersohn M, Bressler R. 1978. Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man. European Journal of Clinical Pharmacology 14:253-259.
  • Eccles R. 2006. Substitution of phenylephrine for pseudoephedrine as a nasal decongestant. An illogical way to control methamphetamine abuse. British Journal of Clinical Pharmacology 63(1):10-14.
  • Greenway FJ, de Jonge L, Blanchard D, Frisard M, Smith, SR. 2004. Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition. Obesity Research 12(7):1152-1157.
  • HC 2009: Health Canada Guidance Document: Nonprescription oral paediatric cough and cold labelling standard. Health Products and Food Branch (HPFB). Minister of Public Works and Government Services Canada.
  • JC 2010a: Justice Canada. 2010. Precursor Control Regulations. Part 1 - Class A Precursors [online]. Ottawa (ON) Department of Justice Canada. [Accessed February 19, 2010]. Available from: http://laws.justice.gc.ca/eng/SOR-2002-359/index.html
  • JC 2010b: Justice Canada. 2010. Food and Drug Regulations. Sections C.01.029, C.01.031 and C.01.031.2 (1). Cautionary Statements and Child Resistant Packages. [online]. Ottawa (ON): Department of Justice Canada. [Accessed 2010 January 08]. Available from: http://laws.justice.gc.ca/en/F-27/C.R.C.-c.870/text.html
  • Lambert MT. 1987. Paranoid psychoses after abuse of proprietary cold remedies. British Journal of Psychiatry 151:548-550.
  • Mills S, Bone K. 2000. Principles and Practice of Phytotherapy. Toronto (ON): Churchill Livingstone.
  • Mills S, Bone K. 2005. The Essential Guide to Herbal Safety. St. Louis (MO): Elsevier Churchill Livingstone.
  • Naik SJ, Freudenberger RS. 2004. Ephedra-associated cardiomyopathy. The Annals of Pharmacotherapy 38:400-403.
  • NLM 2009: United States National Library of Medicine. ChemIDplus Advanced [online]. 2009. Search terms: Pseudoephedrine, Pseudoephedrine Hydrochloride, Pseudoephedrine Sulfate. Bethseda (MD): Specialized Information Services, United States National Library of Medicine, National Institutes of Health, United States Department of Health & Human Services. [Accessed 2009 November 20]. Available from: http://chem.sis.nlm.nih.gov/NLM/chemidheavy.jsp
  • O'Neil MJ, Smith A, Heckelman PE, Budavari S, editors. 2009. The Merck Index [Online]: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14th edition. Whitehouse Station (NJ): Merck & Co., Inc. [Accessed 2010 February 01]. Available from: http://www.medicinescomplete.com/mc/merck/current/03608.htm?q=ephedrine&t=search&ss=text&p=1#_hit
  • Ph. Eur. 2007: European Pharmacopoeia Commission. 2007. European Pharmacopoeia, 6th edition. Strasbourg (FR): Directorate for the Quality of Medicines and HealthCare of the Council of Europe (EDQM).
  • Simons FE, Gu X, Watson WT, Simons KJ. 1996. Pharmacokinetics of the orally administered decongestants pseudoephedrine and phenylpropanolamine in children. Journal of Pediatrics 129(5):729-734.
  • US FDA 2004: United States Food and Drug Administration. Final Rules Declaring Dietary Supplements Containing Ephedrine Alkaloids Adulterated Because They Present an Unreasonable Risk; Final Rule [online]. Federal Register, Volume 69, Number 28, February 11, 2004, Rules and Regulations, Docket Number 1995N-0304. Rockville (MD): United States Department of Health and Human Services, U.S. Food and Drug Administration. [Accessed 2009 November 23]. Available from: http://frwebgate5.access.gpo.gov/cgi-bin/PDFgate.cgi?WAISdocID=999692306001+0+2+0&WAISaction=retrieve
  • USP 32: United States Pharmacopeial Convention. 2009. United States Pharmacopeia and the National Formulary (USP 32 - NF 27). Rockville (MD): The United States Pharmacopeial Convention.
  • Williamson EM. 2003. Potter's Herbal Cyclopaedia: The Authoritative Reference work on Plants with a Known Medical Use. Saffron Walden (GB): The C.W. Daniel Company Limited.

References reviewed

  • Aaronson AL, Ehrlich NJ, Frankel DB, Gutman AA, Aaronson DW. 1968. Effective oral nasal decongestion. A double-blind crossover analysis. Annals of Allergy 26(3):145-150.
  • Burke LM. 2000. Positive drug tests from supplements. Sportscience 4(3):1-5.
  • CRN 2000: Council for Responsible Nutrition. Safety Assessment and Determination of a Tolerable Upper Limit for Ephedra. [online] Mississauga (ON): Cantox Health Sciences International. [Accessed 2009 November 23]. Available from: http://www.crnusa.org/pdfs/Cantoxreport.doc
  • Dawson JK, Earnshaw SM, Graham CS. 1995. Dangerous monoamine oxidase inhibitor interactions are still occurring in the 1990s. Journal of Accident and Emergency Medicine 12:49-51.
  • Dingemanse J, Guentert T, Gieschke R, Stabl M. 1996. Modification of the cardiovascular effects of ephedrine by the reversible monoamine oxidase A-inhibitor moclobemide. Journal of Cardiovascular Pharmacology 28(6):856-861.
  • Drew CD, Knight GT, Hughes DT, Bush M. 1978. Comparison of the effects of D-(-)-ephedrine and L-(+)-pseudoephedrine on the cardiovascular and respiratory systems in man. British Journal of Clinical Pharmacology 6(3):221-225.
  • Elis J, Laurence DR, Mattie H, Prichard BNC. 1967. Modification by monoamine oxidase inhibitors of the effect of some sympathomimetics on blood pressure. British Medical Journal 2:75-78.
  • Empey DW, Young GA, Letley E, John GC, Smith P, McDonnell KA, Bagg LR, Hughes DTD. 1980. Dose-response study of the nasal decongestant and cardiovascular effects of pseudoephedrine. British Journal of Clinical Pharmacology 9:351-358.
  • Farel RM, Fanta CH. 2009. Drug therapy for asthma. New England Journal of Medicine 360(24):2578-2579.
  • Gurley BJ, Gardner SF, White LM, Wang PL. 1998. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Therapeutic Drug Monitoring 20(4):439-445.
  • Haller CA, Jacob P 3rd, Benowitz NL. 2004. Enhanced stimulant and metabolic effects of combined ephedrine and caffeine. Clinical Pharmacology and Therapeutics 75(4):259-273.
  • HC 1996: TPD/NHPD Category IV Labelling Standard, Ephedrine/Pseudoephedrine [online]. Ottawa (ON): Therapeutic Products Directorate, Health Canada.
  • HC 2006: A Summary of NHP/DRUG Classification of TPD Category IV Labelling Standards Ingredients. Natural Health Products Directorate, Health Canada [Accessed 2009 December 23]. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/monograph/list_mono4-eng.php
  • HC 2009: First Nations, Inuit & Aboriginal Health. Drug Benefit List 04:00 Anthistamine Drugs. [Accessed 23 December 2009]. Available from: http://www.hc-sc.gc.ca/fniah-spnia/nihb-ssna/provide-fournir/pharma-prod/med-list/04-00-eng.php
  • HC 2009: Natural Health Products Ingredients Database. Ingredient Search: ephed [online]. Ottawa (ON). Natural Health Products Directorate, Health Canada. [Accessed 2009 November 27]. Available from: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/ingredsReq.do?srchRchTxt=ephed&srchRchRole=-1&lang=eng
  • Herridge CF, A'Brook MF. 1968. Ephedrine psychosis. British Medical Journal 2:160.
  • Hoffman D. 2003. Medical Herbalism: The Science and Practice of Herbal Medicine. Rochester (VT): Healing Arts Press.
  • IOM 2002: Institute of Medicine. 2002. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington: The National Academy of Sciences.
  • Jacobs KM, Hirsch KA. 2000. Psychiatric complications of ma-huang. Psychosomatics 41(1):58-62.
  • JC 2009. Justice Canada. Food and Drug Regulations C.R.C., c. 870. Minister of Justice. Available from http://laws.justice.gc.ca/en/showtdm/cr/C.R.C.-c.870.
  • Laitinen LA, Empey DW, Bye C, Britton MG, McDonnell K, Hughes DTD. 1982. A comparison of the bronchodilator action of pseudoephedrine and ephedrine in patients with reversible airway obstruction. European Journal of Clinical Pharmacology 23:107-109.
  • MHRA 2005: Medicines and Healthcare products Regulatory Agency. The Medicines (Retail Sale or Supply of Herbal Remedies) Order 1977; S.I. 1977/2130 (UK).Available from: http://www.mhra.gov.uk/home/groups/es-herbal/documents/websiteresources/con009294.pdf
  • MHRA 2009: MHRA Public Assessment Report - Controlling the risk of misuse of medicines containing pseudoephedrine and ephedrine. 2009. Medicines and Healthcare products Regulatory Agency. London (UK).
  • Mizoguchi H, Wilson A, Jerdack GR, Hull JD, Goodale M, Grender JM, Tyler BA. 2007. Efficacy of a single evening dose of syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate in subjects with multiple common cold symptoms. International Journal of Clinical Pharmacology and Therapeutics 45(4):230-236.
  • Mortimer EA. 1977. Drug toxicity from breast milk? Pediatrics 60(5):780-781.
  • NAPRA 2009: Outline of National Drug Schedules. Search: ephedr [online]. Ottawa (ON). National Association of Pharmacy Regulatory Authorities. [Accessed 2009 December 17]. Available from: http://napra.ca/pages/Schedules/Search.aspx
  • Salem CB, Slim R, Denguezli M, Sriha B, Hmouda H, Bouraoui K. 2008. Pseudoephedrine-induced acute generalized exanthematous pustulosis. The International Society of Dermatology 47:418-419.
  • Slodki SJ, Montgomery CA. 1965. Clinical comparison of oxymetazoline and ephedrine in nasal congestion. Current Therapeutic Research, Clinical and Experimental 7:19-22.
  • TGA 2008: Australian Therapeutic Goods Administration. Personal Import Scheme for Unapproved Medicines [online]. Symonston (AU): Australian Government Department of Health and Ageing, Therapeutic Goods Administration. [Accessed 2009 November 23]. Available from: http://www.tga.gov.au/import/persimp.htm
  • Theoharides TC. 1997. Sudden death of a healthy college student related to ephedrine toxicity from a ma huang-containing drink. Journal of Clinical Psychopharmacology 17(5)437-439.
  • US FDA 1993: United States Food and Drug Administration. Cold, Cough, Allergy, Bronchodilator and Antiasthmatic Drug Products for Over-the-Counter Human Use; Amendment of Final Monograph for OTC Bronchodilator Drug Products [online]. Federal Register, Volume 58, Number 201, October 20,1993, Final Rule. Docket Number 91N-0323. Rockville (MD): Department of Health and Human Services, U.S. Food and Drug Administration. [Accessed 2009 November 23]. Available from: http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm116064.pdf
  • US FDA 1997: United States Food and Drug Administration. Dietary Supplements Containing Ephedrine Alkaloids [online]. Federal Register, Volume 62, Number 107, June 4,1997, Proposed Rule. Docket Number 95N-0304. Rockville (MD): Department of Health and Human Services, U.S. Food and Drug Administration. [Accessed 2009 November 23]. Available from: http://frwebgate1.access.gpo.gov/cgi-bin/TEXTgate.cgi?WAISdocID=999886443355+0+1+0&WAISaction=retrieve
  • White LM, Gardner SF, Gurley BJ, Marx MA, Wang PL, Estes M. 1997. Pharmacokinetics and cardiovascular effects of ma huang (Ephedra sinica) in normotensive adults. The Journal of Clinical Pharmacology 37:116-122.
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Appendix 1: Derivation of dosage quantities for Pseudoephedrine

Minimum dosage:

children 6-12 years: 30 mg (Simons et al. 1996)

Maximum dosage:

children 6-12 years: 120 mg
24 h 6 h half life x 30 mg per single dosage (Simons et al. 1996; Dickerson et al. 1978)

.

Appendix 2: Information from Pediatric Cough and Cold Guidance Document Regarding Pseudoephedrine Usage (HC 2009).

PHARMACEUTICAL FORMS

The acceptable dosage forms are as follows:

  • Immediate release solid oral dosage forms such as tablets, caplets, chewable tablets, effervescent tablets, powders.
  • Oral liquid formulations such as suspension, syrup, elixir, tincture or drops.
  • Single ingredient thin strips.

Unacceptable dosage forms are as follows:

  • Modified dose release (e.g. liquid extended release, solid oral sustained release, bi-layer formulations or enteric coated products).
  • Products that require evaluation of animal sourced ingredients (e.g. animal tissue based gelatin capsules).
  • Novel dosage forms: e.g., multiple ingredient thin strips, lollipops, popsicles/freezer pops.

INDICATIONS

Acceptable Indications

  • to temporarily relieve the symptoms of the common cold
  • temporary relief of nasal congestion/pressure due to common colds.
  • temporary relief of stuffiness due to common colds.

Unacceptable Indications

  • relief of nasal symptoms other than runny nose and sneezing (for antihistamine)
  • alleviate nasal congestion (for antihistamine)
  • treat lower respiratory tract conditions (including infections and asthma)
  • bronchitis
  • sinusitis
  • relief of sinus pressure/congestion (for decongestant)
  • promote sinus drainage
  • coughs due to allergies or inhaled irritants (for antitussives and expectorants)
  • chest coughs (for antitussives and expectorants)
  • influenza/flu
  • allergy/hay fever symptoms
  • relief of wet cough (for antitussives)
  • relief of dry cough (for expectorant)
  • sleep aid (e.g., relieves sneezing, runny nose and helps you get to sleep)

DOSAGE DIRECTIONS

Dosage for Children 6 to under 12 years

Pseudoephedrine hydrochloride and sulphate 30mg every 4-6 hours 120mg

.

Appendix 3: Background on Monograph

This monograph is intended to serve as a guide to industry for the preparation of Product Licence Applications (PLA) and labels for natural health product market authorization. It is not intended to be a comprehensive review of the medicinal ingredient. It is a referenced document to be used as a labelling standard. Note: Text in parentheses is additional optional information which can be included on the PLA and product labels at the applicant's discretion. The solidus (/) indicates that the terms are synonyms or that the statements are synonymous. Either term or statement may be selected by the applicant.