PSEUDOEPHEDRINE

Children 6-11 years

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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

• 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 statements are synonymous. Either term or statement may be selected by the applicant.

Compliance with Precursor Control Regulations:

The Precursor Control Regulations (PCR) (JC 2018a) 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

September 25, 2018

Proper name(s), Common name(s), Source material(s)

Table 1. Proper name(s), Common name(s), Source material(s)

Proper name(s)	Common name(s)	Source material(s)
		Common name(s)
(1S,2S)-2-Methylamino-1-phenylpropan-1-ol (alphaS)-alpha-[(1S)-1-(Methylamino)ethyl]benzenemethanol d-psi-Ephedrine	Pseudoephedrine	Pseudoephedrine Pseudoephedrine hydrochloride Pseudoephedrine sulfate

References: Proper names: NLM 2018, O'Neil et al. 2018; Common name: NLM 2018, O'Neil et al. 2018; Source materials: NLM 2018, O'Neil et al. 2018.

Route of Administration

Oral

Dosage Form(s)

This monograph excludes foods or food-like dosage forms as indicated in the Compendium of Monographs Guidance Document.

Acceptable dosage forms for any age category listed in this monograph for the specified route of administration are listed in the Compendium of Monographs Guidance Document.

Use(s) or Purpose(s)

• Used as a decongestant (for common cold) (O'Neil et al. 2018; HC 2009; Williamson 2003; Mills and Bone 2000; Bright et al. 1981; Bye et al. 1980).
• Used to relieve nasal congestion (due to the common cold) (O'Neil et al. 2018; HC 2009; Williamson 2003; Mills and Bone 2000; Bright et al. 1981; Bye et al. 1980).
• Nasal decongestant (O'Neil et al. 2018; HC 2009; Williamson 2003; Mills and Bone 2000; Bright et al. 1981; Bye et al. 1980).

Dose(s)

Subpopulation(s)

Children 6 to 11 years

Quantity(ies)

30-120 milligrams pseudoephedrine per day; Not to exceed 30 milligrams per single dose (Simons et al. 1996; Dickerson et al. 1978).

Direction(s) for use

• Take a single dose every 4-6 hours up to 4 times a day (HC 2009).
• Do not give with any other cough and cold medications since harm may occur (HC 2009).

Duration(s) of Use

Consult a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 7 days (HC 2009; US FDA 2004).

Risk Information

Caution(s) and warning(s)

• Keep out of reach of children (HC 2009).
• Consult a health care practitioner/health care provider/health care professional/doctor/ physician if symptoms persist or worsen.
• Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to combining this product with other medications, including natural health products, prescription drugs or non-prescription drugs (HC 2009).
• Consult a health care practitioner/health care provider/health care professional/doctor/ physician prior to use if the child has cardiovascular disease, diabetes, glaucoma, pre-existing psychiatric/behavioural conditions, renal dysfunction, seizure/central nervous system disorders or thyroid problems (Brinker 2010; HC 2009; Eccles 2006; Bensky et al. 2004; Williamson 2003; Blumenthal et al. 2000; Mills and Bone 2000; Simons et al. 1996; Lambert 1987).
• Consult a healthcare practitioner/health care provider/health care professional/doctor/ physician prior to use if the child is taking other products which contain caffeine, ephedrine, phenylpropanolamine or pseudoephedrine (Brinker 2010; Mills and Bone 2005; Greenway et al. 2004; Naik and Freudenberger 2004).
• Call a Poison Control Centre or health care practitioner/health care provider/health care professional/doctor/physician immediately in case of overdose, even if you do not notice any signs or symptoms (HC 2009).
• To mitigate the potential risk to the health of children, it is recommended that child resistant packaging/containers be used as described in Sections C.01.001(2) to (4), and subsection C.01.031(1) (a) (i) of the Food and Drug Regulations (JC 2018b).

Contraindication(s)

No statement required.

Known adverse reaction(s)

Stop use if allergic reactions, breathing difficulties, convulsions, drowsiness, hallucinations or rapid heart rate occur (Blumenthal et al. 2000; Dickerson et al. 1978).

Non-medicinal ingredients

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

Storage conditions

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

Specifications

• The finished product specifications must be established in accordance with the requirements described in the Natural and Non-prescription Health Product Directorate (NNHPD) Quality of Natural Health Products Guide.
• The medicinal ingredient must comply with the requirements outlined in the NHPID.

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. Herb Contraindications and Drug Interactions, 4^th edition. Sandy (OR): Eclectic Medical Publications; 2010.
• 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 2018a: Justice Canada. 2018. Precursor Control Regulations. Part 1 - Class A Precursors [online]. Ottawa (ON) Department of Justice Canada. [Accessed 2018 July 13]. Available from: http://laws-lois.justice.gc.ca/eng/regulations/SOR-2002-359/index.html
• JC 2018b: Justice Canada. 2018. 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 2018 July 13]. Available from: http://laws-lois.justice.gc.ca/eng/regulations/c.r.c.,_c._870/page-97.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 2018: United States National Library of Medicine. ChemIDplus Advanced [online]. 2018. 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 2018 July 13]. Available from: https://chem.nlm.nih.gov/chemidplus/
• O'Neil MJ, Smith A, Heckelman PE, Budavari S, editors. 2018. The Merck Index [Online]: An Encyclopedia of Chemicals, Drugs, and Biologicals, 14^th edition. Whitehouse Station (NJ): Merck & Co., Inc. [Accessed 2018 July 13]. Available from: http://www.medicinescomplete.com/mc/merck/current/03608.htm?q=ephedrine&t=search&ss=te xt&p=1#_hit
• Ph. Eur. 2007: European Pharmacopoeia Commission. 2007. European Pharmacopoeia, 6^th 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 2018 July 13]. Available from: https://www.gpo.gov/fdsys/pkg/FR-2004-02-11/pdf/04-2912.pdf
• USP 32 2009: 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

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• 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 12:4951.
• 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.
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• HC 1996: 1996 TPD Labelling Standard Ephedrine/Pseudoephedrine. Ottawa (ON): Therapeutic Products Directorate, Health Canada.
• HC 2006: A Summary of NHP/DRUG Classification of TPD Category IV Monographs and Labelling Standards Ingredients. Natural Health Products Directorate, Health Canada [Accessed 2009 December 23]. Available from: http://www.hc-sc.gc.ca/dhpmps/prodnatur/applications/licen-prod/monograph/list_mono4-eng.php
• HC 2009: First Nations, Inuit & Aboriginal Health. Drug Benefit List 04:00 Anthistamine Drugs. [Accessed 2009 December 23]. Available from: http://www.hc-sc.gc.ca/fniah-spnia/nihbssna/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
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• 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
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