Counterirritants

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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.

Definition of Counterirritant

An externally applied substance that causes irritation or mild inflammation of the skin for the purpose of relieving pain in muscles or joints by reducing inflammation in deeper adjacent structures (Medline 2012; MediLexicon 2012; US FDA 1983).

Notes

Date

April 29, 2019

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

Table 1. Proper name(s), Common name(s), Source material(s) - Medicinal ingredients
Proper name(s) Common name(s) Source Ingredient(s) Source material(s)1
Common name(s) Proper name(s) Part(s)
  • 3-isothiocyanato-1-propene
  • Allyl isothiocyanate
  • Isothiocyanic acid allyl ester
Allyl isothiocyanate

Allyl isothiocyanate

N/A

N/A

Ammonium hydroxide

  • Ammonia water
  • Ammonium hydroxide

Ammonium hydroxide

N/A

N/A

  • (1R, 4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one
  • d-camphor
  • (+)- Camphor
  • Camphor
  • d-camphor
  • natural camphor

d-camphor

N/A

N/A

  • (1RS, 4RS)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one
  • dl-camphor
  • (+-)- camphor
  • dl-camphor
  • Racemic camphor

dl-camphor

N/A

N/A

  • (6E)-N-[(4-Hydroxy-3-methoxyphenyl) methyl]-8-methyl-6-nonenamide
  • (E)-8-methyl-N-vanillyl-6- nonenamide

Capsaicin

Capsaicin

N/A

N/A

Eucalyptus globulus

  • Eucalyptus essential oil
  • Eucalyptus Globulus Leaf essential oil

N/A

Eucalyptus globulus

Leaf

  • 1,3,3-Trimethyl-2-oxabicyclo(2.2.2) octane
  • 1,8 Cineole
  • 1,8-Epoxy-p-menthane
  • Cineole
  • Eucalyptol

Eucalyptol

N/A

N/A

  • 1H-imidazole-4-ethanamine, dihydrochloride
  • 2-imidazol-4-ylethylamine dihydrochloride
  • 4-(2-aminoethyl) imidazole dihydrochloride

Histamine dihydrochloride

Histamine dihydrochloride

N/A

N/A

  • (1R,2S,5R)-rel-5-methyl-2-(1-methylethyl)-cyclohexanol
  • (1RS,2RS,5RS)-(±)-5-methyl-2-(1-methylethyl) cyclohexanol
  • dl-Menthol
  • dl-Menthol
  • Racemic Menthol

dl-menthol

N/A

N/A

  • (1R,2S,5R)-5-Methyl-2-(1-methylethyl) cyclohexane
  • (1R,2S,5R)-5-methyl-2-(propan-2 yl) cyclohexan-1-ol
  • l-Menthol
  • l-menthol
  • Menthol

l-menthol

N/A

N/A

3-pyridinecarboxylic acid methyl ester

Methyl nicotinate

Methyl nicotinate

N/A

N/A

  • 2-(Methoxycarbonyl) phenol
  • 2-Hydroxybenzoic acid methyl ester
  • Methyl 2-hydroxybenzoate

Methyl salicylate

Methyl salicylate

N/A

N/A

Turpentine essential oil

  • Turpentine essential oil
  • Turpentine oil

Turpentine essential oil

N/A

N/A

Table 1 footnotes

Table 1 footnote 1

All ingredients, except ammonium hydroxide, must be pharmacopoeial grade (see Table 6 in the specifications below).

Return to table 1 footnote 1 referrer

References: Ph.Eur. 2013, BP 2012, Merck 2012, NLM 2012, USP 36, ChEBI 2011, CTFA 2008, Bruneton 1999.

Table 2. Proper name(s), Common name(s), Source material(s) - Complementary ingredients (safety only)
Proper name(s) Common name(s) Source Ingredient(s) Source material(s)1
Common Name(s) Proper name(s) Part(s)

Syzygium aromaticum

Clove essential oil

N/A

Syzygium aromaticum

Flower bud

  • 1-methyl-3-hydroxy-4- isopropylbenzene
  • 5-methyl-2-(propan-2-yl) phenol
  • 5-methyl-2-(1-methylethyl)-phenol
  • 5-methyl-2-isopropyl -1-phenol

Thymol

Thymol

N/A

N/A

Table 2 footnotes

Table 1 footnote 1

All ingredients must be pharmacopoeial grade (see Table 6 in the specifications below).

Return to table 1 footnote 1 referrer

References: Proper name: Ph.Eur. 2013, BP 2012, Merck 2012, NLM 2012, USP 36 2013, ChEBI 2011, Bruneton 1999.

Route of Administration

Topical

Dosage Form(s)

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

Plaster, compress or patch

Menthol, methyl salicylate, eucalyptus oil and eucalyptol are the only medicinal ingredients allowed in these forms (Higashi et al. 2010).

Use(s) or Purpose(s)

Products containing an ingredient in Table 1

Temporarily relieves aches and pains of muscles and joints associated with one or more of the following: simple backache, lumbago, strains and sprains (involving muscles, tendons, and/or ligaments), and arthritis.

Dose(s)

Subpopulation(s)

Children 2 to 11 years, Adolescents 12 to 17 years and Adults 18 years and older

Quantity(ies)

Table 3. Medicinal Ingredient Doses
Medicinal Ingredients Doses

Allyl isothiocyanate

0.5 - 5.0 %

Ammonium hydroxide

1.0 - 2.5 %

d-camphor

3 - 11 %

dl-camphor

3 - 11 %

Capsaicin

0.025 - 0.25 %

Eucalyptus essential oil

0.5 - 25.0 %

Eucalyptol

0.5 - 20.0 %

Histamine dihydrochloride

0.025 - 0.1 %

l-menthol

1.25 - 16 %

dl-menthol

1.25 - 16 %

Methyl nicotinate

0.25 - 1.0 %

Methyl salicylate

10 - 30 %

Turpentine essential oil

6 - 50 %

References: JC 2012, AU TGA 2007, Janjua et al. 2004, ESCOP 2003, APhA 2002, WHO 2002, Blumenthal et al. 2000, CPhA1996, Mathias et al. 1995, US FDA 1983, 1979.

Table 4. Complementary Ingredients Doses (Safety only)
Complementary Ingredients Doses

Clove essential oil

0.1 - 2.0 %

Thymol

0.1 - 2.0 %

References: US FDA 1979.

Permitted combinations

Table 5. Permitted combinations1
Groups2 Ingredients

A

Allyl isothiocyanate, ammonium hydroxide, methyl salicylate, turpentine essential oil

B1

Camphor, menthol

B2

Eucalyptus essential oil, eucalyptol

C

Histamine dihydrochloride, methyl nicotinate

D

Capsaicin

E

Thymol, clove essential oil

Table 5 footnotes

Table 5 footnote 1

See Appendix 1 for grouping rationale.

Return to table 1 footnote 1 referrer

Table 5 footnote 2

Permitted combinations for all groups are supported by US FDA 1979, except for Group E which is supported by Merck 2012, Martindale 2010, and Leung and Foster 2003.

Return to table 2 footnote 2 referrer

Direction(s) for use

All products

For children and adolescents 2-12 years

Application should be supervised by an adult (Ragucci et al. 2007; Love et al. 2004).

Products in liquid or semi-solid form

Apply thinly and evenly to affected area up to 3-4 times per day. Rub and/or massage into skin until solution vanishes (US FDA 1979).

Products in compress, plaster or patch form

Do not leave on skin for more than 8 hours (Higashi et al. 2010).

Products in pump spray form

Do not inhale (APhA 2002).

Duration(s) of Use

Products containing capsaicin as a single medicinal ingredient

All other products (including multiple ingredient products containing capsaicin)

Consult a health care practitioner/health care provider/health care professional/doctor/physician for use beyond 7 days (US FDA 1983).

Risk Information

Caution(s) and warning(s)

All products

Products containing camphor, menthol, and/or methyl salicylate

Consult a health care practitioner/health care provider/health care professional/ doctor/physician prior to use if you are pregnant or breastfeeding (Brinker 2001).

Products containing methyl salicylate and/or methyl nicotinate

Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are taking anticoagulant medications (Martindale 2010; APhA 2002).

Products containing methyl nicotinate

Consult a health care practitioner/health care provider/health care professional/doctor/physician prior to use if you are taking medication or natural health products that cause dilation of blood vessels (APhA 2002).

Contraindication(s)

No statement required.

Known adverse reaction(s)

All products

Stop use if hypersensitivity/allergy, rashes and/or burning discomfort occur (Martindale 2010; Zhang et al. 2008; Hoffman 2003; APhA 2002; McCleane 2000).

Products containing capsaicin

Stop use if headache and/or redness occur (Zhang et al. 2008; APhA 2002; McCleane 2000).

Products containing menthol

Stop use and get medical help right away if you experience pain, swelling or blistering (HC 2017).

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 in airtight, light-resistant container at room temperature (Ph.Eur. 2013; BP 2012; USP 36).

Specifications

Table 6. Monographs published in the British (BP), European (Ph.Eur.), and American (USP) Pharmacopoeias
Pharmacopoeia Monographs

BP 2012

  • Natural Camphor
  • Racemic Camphor
  • Cineole
  • Histamine Dihydrochloride
  • Methyl Nicotinate
  • Methyl Salicylate
  • Thymol

Ph.Eur. 2013

  • D-Camphor
  • Camphor, racemic
  • Cineole
  • Clove Oil
  • Eucalyptus Oil
  • Histamine dihydrochloride
  • Menthol, Racemic
  • Methyl Nicotinate
  • Methyl Salicylate
  • Thymol
  • Turpentine Oil

USP 36 - NF 31

  • Allyl isothiocyanate
  • Camphor
  • Capsaicin
  • Clove oil
  • Eucalyptol
  • Menthol
  • Methyl Salicylate
  • Thymol

References Cited

References Reviewed

Appendix 1

Table 7. Groupings based on effects/modes of action (US FDA 1983; US FDA 1979)
Groups Ingredients Effects/Modes of action1

A

Allyl isothiocyanate, ammonium hydroxide, methyl salicylate, turpentine essential oil

Redness, irritation; relatively more potent than other commonly used counterirritants

B1

Camphor, menthol

Cooling/warmth/tingling sensation, organoleptic properties

B2

Eucalyptus essential oil, eucalyptol

Cooling/warmth/tingling sensation, organoleptic properties

C

Histamine dihydrochloride, methyl nicotinate

Vasodilation, vasoactive properties

D

Capsaicin

Irritation without rubefaction, although about equal in potency to Group A do not produce redness

Table 7 footnotes

Table 7 footnote 1

These are not uses or purposes.

Return to table 7 footnote 1 referrer