You are here

Consultation: Proposed amendments to the Poisons Standard - ACMS, ACCS and Joint ACMS/ACCS meetings, November 2020

16 September 2020

We have changed the way to make submissions.

Submissions now should be provided through our consultation hub. Any submission about any of the proposals to amend the Poisons Standard will be considered at the next meeting of the Advisory Committee on Medicines Scheduling (ACMS), meeting of the Advisory Committee on Chemicals Scheduling (ACCS), or a joint meeting of these two committees.

This consultation closes on 28 September 2020.

Scheduling amendments referred to expert advisory committee

Subdivision 3D.2 of the Therapeutic Goods Regulations 1990 (the Regulations) sets out the procedure to be followed where the Secretary receives an application under section 52EAA of the Therapeutic Goods Act 1989 (the Act) to amend the current Poisons Standard or decides to amend the Poisons Standard on his or her own initiative and decides to refer the proposed amendment to an expert advisory committee. These include, under regulation 42ZCZK, that the Secretary publish (in a manner the Secretary considers appropriate) the proposed amendment to be referred to an expert advisory committee, the committee to which the proposed amendment will be referred, and the date of the committee meeting. The Secretary must also invite public submissions to be made to the expert advisory committee by a date mentioned in the notice as the closing date, allowing at least 20 business days after publication of the notice.

In accordance with regulation 42ZCZK of the Regulations, the Secretary invites public submissions on scheduling proposals referred to the November 2020 meetings of the Advisory Committee on Medicines Scheduling (ACMS #32), the Advisory Committee on Chemical Scheduling (ACCS #29) and the Joint Advisory Committee on Medicines and Chemicals Scheduling (Joint ACMS-ACCS #26).

Submissions must be received by close of business 28 September 2020.

Note

New text is shown as green, larger font, with a horizontal line above it.

Deleted text is shown as red, smaller font, with a strikethrough.

1 Proposed amendments referred for scheduling advice to ACMS #32

CAS Number:

Amygdalin: 29883-15-6

Hydrocyanic acid: 74-90-8

Alternative names

Amygdalin: D-mandelonitrile-β-D-glucoside-6-β-glucoside; mandelonitrile-&bet;-gentiobioside; Vitamin B17

Hydrocyanic acid: Hydrogen cyanide; formonitrile; prussic acid

Applicant

Private applicant

Current scheduling

Amygdalin

Schedule 10

AMYGDALIN for therapeutic use.

Index

AMYGDALIN

Schedule 10

Hydrocyanic acid

Schedule 7

HYDROCYANIC ACID except:

  1. when included in Schedule 4; or
  2. its salts and derivatives other than cyanides separately specified in this Schedule.

Schedule 4

HYDROCYANIC ACID for therapeutic use.

Appendix F, Part 3
Poison Warning Statements Safety Directions
HYDROCYANIC ACID when included in Schedule 7. 13 (May be fatal if inhaled, swallowed or absorbed through skin) 4 (Avoid contact with skin), 8 (Avoid breathing dust (or) vapour (or) spray mist)
Appendix G
Poison Concentration (quantity per litre or kilogram)
HYDROCYANIC ACID 1 microgram
Appendix J, Part 2
Poisons Authorisation Considerations
HYDROCYANIC ACID AND CYANIDES P (additional restrictions on possession)

Index

HYDROCYANIC ACID
cross reference: CYANIDES

Schedule 7
Schedule 4
Appendix F, Part 3
Appendix J, Part 2

Proposed scheduling

A request has been made to amend the Poisons Standard as follows:

Amygdalin

Schedule 10 - Amend Entry

AMYGDALIN for therapeutic use except when included in or expressly excluded from Schedule 4.

Schedule 4 - New Entry

AMYGDALIN when included as a natural component in traditional Chinese medicines for oral use in adults except when the maximum recommended daily dose is equivalent to no greater than 5 mg of amygdalin.

Index

AMYGDALIN

Schedule 10

Schedule 4

Hydrocyanic acid

Schedule 4 - Amend Entry

HYDROCYANIC ACID for therapeutic use except when present as a natural component of amygdalin in traditional Chinese medicines for oral use in adults.

Index - Amend Entry

HYDROCYANIC ACID
cross reference: CYANIDES

Schedule 7
Schedule 4
Appendix F, Part 3
Appendix G
Appendix J, Part 2

Key uses / expected use

Medicines

Reasons for proposal put forward by the applicant

  • Amygdalin is a cyanogenic glycoside found naturally in many plants including cassava, sorghum, lima beans, bitter almonds, apricot kernels and seeds of other plants in the Prunus genus.
  • Many traditional Chinese medicines are formulated to include one or more of these plant ingredients, usually in combination with other traditional Chinese herbs. Under the current scheduling arrangements, products that contain amygdalin in any quantity cannot be used in therapeutic goods, which means that many formulated TCM products that are freely available in other countries are not available to Australian TCM practitioners.
  • This application proposes excluding amygdalin from Schedule 10 when included as a natural component in traditional Chinese medicines for oral use in adults and including it in Schedule 4 with a cut-off to unscheduled at a maximum daily adult dose of 5 mg or less.
  • The selected cut-off of 5 mg per maximum daily dose is based on animal studies and assessment by a wide range of regulatory and expert committees that an oral intake of 5 to 20 µg/kg/d cyanide (equivalent to 5.1 to 20.3 mg/d amygdalin for a 60 kg adult) is considered to present no appreciable risk. It is substantially less than the legal limit in many foods for human consumption in Australia and New Zealand.
  • By way of comparison 100 g of confectionary could legally contain more than 8 times this proposed maximum daily dose and one standard drink of red wine could legally contain more than 4 times this dose.
  • An associated change to exclude hydrocyanic acid from Schedule 4 when present as a natural component of amygdalin in traditional Chinese medicines for oral use in adults is also proposed.
  • The effect of the changes would be:
    • To make traditional Chinese medicine products containing very low doses of amygdalin available without prescription; and
    • To allow medically qualified traditional Chinese medicine practitioners to prescribe traditional Chinese medicines containing higher doses of amygdalin as Schedule 4 medicines (e.g. in registered complementary medicines or via the TGA's Special Access Scheme).

Australian regulations

International regulations

  • Amygdalin has not been approved for use by the U.S Food and Drugs Administration or the European Commission. Import of amygdalin is prohibited in the U.S, UK and Europe.
  • In Canada, no health products containing B17 or amygdalin have been authorised to treat cancer or any other condition.
  • Amygdalin was first entered in the New Zealand Inventory of Chemicals (NZIoC) on 1 December 2006. According to the New Zealand Medicines and Medical Devices Safety Authority (MedSafe) amygdalin is available as follows in New Zealand:
    Ingredient Conditions Classification
    Amygdalin At all strengths Prescription

Footnotes

CAS Number:

13956-29-1

Alternative names

CBD; 2-(6-Isopropenyl-3-methyl-2-cyclohexen-1-yl)-5-pentyl-1,3-benzenediol

Applicant

Private applicant

Current scheduling

Schedule 4

CANNABIDIOL in preparations for therapeutic use where:

  1. cannabidiol comprises 98 per cent or more of the total cannabinoid content of the preparation; and
  2. any cannabinoids, other than cannabidiol, must be only those naturally found in cannabis and comprise 2 per cent or less of the total cannabinoid content of the preparation.

Index

CANNABIDIOL
cross reference: NABIXIMOLS, CANNABIS, TETRAHYDROCANNABINOLS

Schedule 4

Proposed scheduling

A request has been made to amend the Poisons Standard as follows:

Schedule 4 - Amend Entry

CANNABIDIOL in preparations for therapeutic use where:

  1. cannabidiol comprises 98 per cent or more of the total cannabinoid content of the preparation; and
  2. any cannabinoids, other than cannabidiol, must be only those naturally found in cannabis and comprise 2 per cent or less of the total cannabinoid content of the preparation; or
  3. cannabidiol is a synthetic or semi-synthetic copy of the molecule and comprises 98 per cent or more of the total cannabinoid content of the preparation and any other synthetic or semi-synthetic cannabinoids; and
  4. any impurities in the synthesis of the cannabidiol, other than cannabidiol, must comprise 2 per cent or less of the total cannabinoid content of the preparation.

Key uses / expected use

Medicines

Reasons for proposal put forward by the applicant

  • CBD can be obtained from synthetic sources. There is no mention of CBD from synthetic sources in the Schedule 4 entry although the chemical structure is the same as that found naturally in the Cannabis sativa plant.
  • Synthetic (-) CBD has a similar safety profile when compared with naturally derived CBD, related substances and impurities considered.
  • Natural and synthetic (-) CBD show identical biological activities. The impurity profile and related substances were studied in detail before the release of 'Safety of low dose Cannabidiol' by TGA. We propose that the amended entry to Schedule 4 would benefit from having mention of other impurities.

Australian regulations

International regulations

  • In a letter dated 24 Jan 2019 from the Director General of the WHO to the Secretary General of the United Nations, on the basis of the 12 to 16 November 2018 reviews conducted by the WHO's Expert Committee on Drug Dependence (ECDD) on cannabis and cannabis related substances (including CBD), the WHO recommended that preparations containing predominantly CBD with not more than 0.2% THC should not be placed under international drug control (WHO 2019)[14]:

    "To give effect to the recommendation of the fortieth meeting of the ECDD that preparations considered to be pure cannabidiol (CBD) should not be scheduled within the International Drug Control Conventions by adding a footnote to the entry for cannabis and cannabis resin in Schedule I of the Single Convention on Narcotic Drugs (1961) to read "Preparations containing predominantly cannabidiol and not more than 0.2 percent of delta-9-tetrahydrocannabinol are not under international control".

  • The European Medicines Agency (EMA)[15] has authorised one prescription cannabidiol medicines for the treatment of Lennox-Gastaut syndrome and Dravet syndrome (two rare and severe forms of epilepsy) patients aged 2 years and older.
  • The European Union guides all member states that hemp should not exceed a THC limit of 0.2%. In January 2019, European Union's Novel Food regime, led to the classification of all extracted cannabinoids as "novel". Novel Food is defined as food that had not been used for human consumption to a significant degree in the European Union before 15th May 1997. According to this new classification, CBD products require pre-market authorisation[16].
  • In the United States (U.S.), the FDA has approved one CBD prescription product for the treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age or older. It is currently illegal to market CBD by adding it to a food or labelling it as a dietary supplement. Some CBD products are being marketed with unproven medical claims and are of unknown quality. In 2018, the Farm Bill[17] legalized the production and sale of hemp and its extracts. Hemp derived CBD containing less than 0.3 percent THC, is exempted under federal law, however some states still have legal restrictions on the possession of CBD.
  • In Canada, there is one approved product containing a CBD/THC combination, available as a prescription medicine. Phytocannabinoids are regulated under the Cannabis Act[18]. Under the Cannabis Act, CBD products remain strictly regulated and are only legal when sold in compliance with the Act and its regulations. The provinces and territories are responsible for determining how cannabis is distributed and sold within their jurisdictions. CBD and products containing CBD, such as cannabis oil, may only be sold by a provincially or territorially-authorised cannabis retailer or a federally-licensed seller of cannabis for medical purposes.
  • In the United Kingdom (U.K), CBD in its pure form is not classed as a controlled drug under the Misuse of Drugs Act (MDA) 1971/Misuse of Drugs Regulations (MDR) 2001. However, noting the difficulty to isolate pure CBD, based on the precautionary principles, a CBD containing product would be controlled under the MDA 1971/MDR 2001 as a result if it's other cannabinoid content.[19] The UK Food Standards Agency confirmed the novel food status of CBD extracts in January 2019 and has set a deadline of 31 March 2021 for companies marketing CBD extracts as foods or foods supplements, to submit Novel Food approval applications.[20]
  • In New Zealand, cannabinol is classified as a prescription only medicine, where the tetrahydrocannabinols (THCs) and specified substances within the product must not exceed 2 percent of the total CBD, tetrahydrocannabinol (THC) and other specified substances. If a product contains CBD but does not meet the definition of a CBD product, it is a 'controlled drug' and is subject to the regulatory requirements of the Misuse of Drugs Act.[21]

Footnotes

CAS Number:

202189-78-4

Alternative names

2-[4-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)piperidin-1- yl)ethyl)phenyl]-2-methylpropionic acid; p-[2-[4-[1-(2-ethoxyethyl)-2-benzimidazolyl]piperidino]ethyl]-α-methylhydratropic acid

Benzeneacetic acid, 4-[2-[4-[1-(2-ethoxyethyl)-1H-benzimidazol-2-yl]-1-piperidinyl]ethyl]-α,α-dimethyl-

Applicant

Private applicant

Current scheduling

Bilastine is not specifically scheduled in the Poisons Standard. However, bilastine is captured by the current Schedule 4 and Appendix F, Part 3 entries for antihistamines as follows:

Schedule 4

ANTIHISTAMINES except:

  1. when included in Schedule 2 or 3; or
  2. when separately specified in this Schedule.
Appendix F, Part 3
Poison Warning Statements Safety Directions

ANTIHISTAMINES not separately specified in this Appendix except:

  1. dermal, ocular, parenteral and paediatric preparations;
  2. oral preparations of astemizole, azelastine, desloraradine, fexafendadine, loratadine, terfenadine or cetirizine; or
  3. nasal preparations of azelastine; or
  4. preparations for the treatment of animals.

39 (This medication may cause drowsiness. If affected do not drive a vehicle or operate machinery. Avoid alcohol) or

40 (This medication may cause drowsiness and may increase the effects of alcohol. If affected do not drive a motor vehicle or operate machinery).

Index

ANTIHISTAMINES
cross reference: ASTEMIZOLE, AZELASTINE, DESLORATADINE, FEXOFENADINE, LORATADINE, TERFENADINE, CETIRIZINE

Schedule 4
Appendix F, Part 3

Proposed scheduling

A request has been made to amend the Poisons Standard as follows:

Schedule 2 - New Entry

BILASTINE in preparations for oral use.

Schedule 4 - New Entry

BILASTINE except when included in Schedule 2.

Appendix F, Part 3 - Amend Entry
Poison Warning Statements Safety Directions

ANTIHISTAMINES not separately specified in this Appendix except:

  1. dermal, ocular, parenteral and paediatric preparations;
  2. oral preparations of astemizole, azelastine, desloraradine, fexafendadine, loratadine, terfenadine, bilastine or cetirizine; or
  3. nasal preparations of azelastine; or
  4. preparations for the treatment of animals.

39 (This medication may cause drowsiness. If affected do not drive a vehicle or operate machinery. Avoid alcohol) or

40 (This medication may cause drowsiness and may increase the effects of alcohol. If affected do not drive a motor vehicle or operate machinery).

Index - New Entry

BILASTINE

Schedule 4
Schedule 2
Appendix F, Part 3

Index - Amend Entry

ANTIHISTAMINES
cross reference: ASTEMIZOLE, AZELASTINE, BILASTINE, DESLORATADINE, FEXOFENADINE, LORATADINE, TERFENADINE, CETIRIZINE

Schedule 4
Appendix F, Part 3

Key uses / expected use

Medicine

Reasons for proposal put forward by the applicant

  • This application seeks an amendment to the Poisons Standard to enable the supply of bilastine in oral preparations as Schedule 2 (Pharmacy Only) medicines.
  • Bilastine is a new, second-generation non-sedating antihistamine (NSAH) molecule in Australia. It belongs to the same pharmacological class as fexofenadine, loratadine and cetirizine and is similarly used for the symptomatic treatment of allergic rhinitis (AR) and urticaria.
  • NSAHs are very well-established OTC medicines in Australia and the availability of bilastine as a Schedule 2 medicine is considered appropriate given its risk-benefit and safety profiles are equivalent to existing Schedule 2 and unscheduled molecules in its class.
  • Bilastine has a well-defined safety and tolerability profile, with a wide therapeutic index. As bilastine is highly selective for peripheral H1-receptors and does not cross the blood-brain barrier, incidence of sedation is very low. At the therapeutic dose of 20 mg/day, bilastine does not impact psychomotor performance, enhance the depressant effect of alcohol or lorazepam, nor does it affect the ability to drive and/or operate machinery.
  • The nature of the conditions bilastine is proposed to treat are generally intermittent and self-limiting, and the safe and effective use of second-generation NSAHs for such conditions with minimal instances of misuse and/or abuse has been widely established in Australia for over 20 years.
  • Bilastine is regarded as having a very low risk of harm from inappropriate use and the availability of only a single strength and dosage form for use in all indications with no dose modification recommendations will assist in minimising risks associated with potential medication error.
  • Given the nature of the condition (readily self-diagnosable, commonly intermittent) and the patient population (excellent awareness of their disease and expectations regarding symptomatic relief, rarely consult their doctor about their treatment), the availability of bilastine as a Schedule 2 medicine ensures that those patients who require assistance have access to an appropriately qualified and informed health professional.

Australian regulations

  • According to the TGA Ingredient Database[22], bilastine is:
    • Available for use as an active ingredient in export only and prescription medicines;
    • Not available as an excipient or an equivalent ingredient in any application.
  • As of August 2020, there were no medicines currently active on the Australian Register of Therapeutic Goods (ARTG)[23] that contain bilastine as an active ingredient.
  • Bilastine is not permitted to be included in listed medicines as it is not included in the Therapeutic Goods (Permissible Ingredients) Determination[24] No.3 of 2020.
  • Bilastine is not included in the TGA prescribing medicines in pregnancy database[25].
  • While there are no warning statements pertaining specifically to bilastine in the Therapeutic Goods (Medicines Advisory Statements) Specification 2019[26],the following warning statements pertaining to antihistamines are required to be included on the labelling:
    Substance Conditions Required statement(s)

    Antihistamines

    (Entry 1 of 5)

    including:

    • Alimemazine (trimeprazine)
    • Brompheniramine
    • Chlorphenamine
    • Dexchlorpheniramine
    • Diphenhydramine
    • Doxylamine
    • Pheniramine
    • Promethazine
    • Triprolidine

    when NOT separately specified in this table

    In oral medicines that include dosage instructions for adults and children aged from 'x' years (where 'x' must not be less than 2) when NOT separately specified in this table

    either

    • This medication may cause drowsiness. If affected do not drive a vehicle or operate machinery. Avoid alcohol.

    or

    • This medication may cause drowsiness and may increase the effects of alcohol. If affected do not drive a motor vehicle or operate machinery.
    • Do not give to children under 'x' years of age.
    • and ( if 'x' < 12)
      • Do not give to children between 'x' and 11 years of age, except on the advice of a doctor, pharmacist or nurse practitioner.

    Antihistamines

    (Entry 2 of 5)

    including:

    • Alimemazine (trimeprazine)
    • Brompheniramine
    • Chlorphenamine
    • Dexchlorpheniramine
    • Diphenhydramine
    • Doxylamine
    • Pheniramine
    • Promethazine
    • Triprolidine

    when NOT separately specified in this table

    In oral medicines that ONLY include dosage instructions for CHILDREN aged between 'x' and 'y' years (where 'x' must not be less than 2, and 'y' must not be more than 11) when NOT separately specified in this table

    • This medication may cause drowsiness.
    • Do not give to children under 'x' years of age.
    • Do not give to children between 'x' and 'y' years of age, except on the advice of a doctor, pharmacist or nurse practitioner

    Antihistamines

    (Entry 3 of 5)

    including:

    • Brompheniramine
    • Chlorphenamine
    • Dexchlorpheniramine
    • Diphenhydramine
    • Doxylamine
    • Pheniramine
    • Promethazine
    • Triprolidine

    when NOT separately specified in this table

    In oral preparations indicated for COUGH, COLD OR FLU:

    • which include dosage instructions for adults and children aged from 'x' years (where 'x' must not be less than 6)

    either

    • This medication may cause drowsiness. If affected do not drive a vehicle or operate machinery. Avoid alcohol.

    or

    • This medication may cause drowsiness and may increase the effects of alcohol. If affected do not drive a motor vehicle or operate machinery.
    • Do not give to children under 'x' years of age.
    • and (if 'x' < 12)
      • Do not give to children between 'x' and 11 years of age, except on the advice of a doctor, pharmacist or nurse practitioner.

    Antihistamines

    (Entry 4 of 5)

    including:

    • Brompheniramine
    • Chlorphenamine
    • Dexchlorpheniramine
    • Diphenhydramine
    • Doxylamine
    • Pheniramine
    • Promethazine
    • Triprolidine

    when NOT separately specified in this table

    In oral preparations indicated for COUGH, COLD OR FLU:

    • which ONLY include dosage instructions for CHILDREN aged between 'x' and 'y' years (where 'x' must not be less than 6 and 'y' must not be more than 11)

    This medication may cause drowsiness.

    • Do not give to children under 'x' years of age.
    • and (if 'x' < 12)
      • Do not give to children between 'x' and 11 years of age, except on the advice of a doctor, pharmacist or nurse practitioner.

    Antihistamines

    (Entry 5 of 5)

    including:

    • Diphenhydramine
    • Doxylamine
    • Promethazine

    In oral medicines indicated for SHORT TERM USE IN INSOMNIA:

    • which include dosage instructions for adults and children aged from 'x' years (where 'x' must not be less than 2)

    (Note: Antihistamine medicines indicated for sedation that only include dosage instructions for children aged < 12 years are subject to 'Antihistamines (Entry 2 of 5))

    • This product should be taken on medical or pharmacist advice.
    • Do not give to children under 'x' years of age.
    • either (if the substance is in pregnancy category B or C):
      • If pregnant or [likely/trying] to become pregnant, or if breastfeeding, consult a doctor or pharmacist before use.
    • or (if the substance is in pregnancy category A):

      either

      • Not recommended for use by pregnant or breastfeeding women.

      or

      • If pregnant or breastfeeding, consult a doctor or pharmacist before use.
    • Do not take this medicine for more than a few days.
    • This preparation is to aid sleep. Drowsiness may continue the following day. If affected do not drive or operate machinery. Avoid alcohol.
  • As of August 2020, there were no reports of adverse events for products containing bilastine as an active ingredient on the Database of Adverse Event Notifications (DAEN)[27],
  • As of August 2020, there were no products containing bilastine listed on the Public Chemical Registration Information System Search (PubCRIS)[28].

International regulations

  • Bilastine, 20 mg tablet is an authorised medicine in the European Union (pdf,123kb)[29].
  • According to the Health Products Regulatory Authority of Ireland[30], bilastine 2.5 mg oral solution, 10 mg orodispersible tablets are approved as a prescription medicine for children aged 6 to 11 years with a body weight of at least 20 kg to relieve symptoms of hayfever, other forms of allergic rhinitis and for the treatment of itchy skin rashes including urticaria. Bilastine 20 mg tablets are approved for use in adults and adolescents 12 years of age and older for the symptomatic treatment of seasonal and perennial allergic rhino-conjunctivitis and urticaria.
  • In the United Kingdom (UK)[31], bilastine 20 mg tablets is an approved prescription medicine for the symptomatic treatment of allergic rhino-conjunctivitis (seasonal and perennial) and urticaria in adults and in adolescents 12 years of age and over.
  • While bilastine is included in the United States Food and Drug Administration (USFDA) Substance Registration System[32] this does not imply any regulatory review or approval of the substance.
  • According to the Health Canada Drug Product database[33], bilastine 20 mg tablets have been approved as a prescription antihistamine medicine since March 2016.
  • The New Zealand Medicines and Medical Devices Safety Authority (MedSafe)[34] classifies bilastine as both a Prescription and Pharmacy only medicine. As a Pharmacy only medicine, bilastine is available in divided solid dosage forms for oral use containing 20 milligrams or less for the treatment of the symptoms of allergic rhino-conjunctivitis (seasonal and perennial) and urticaria. All other forms or strengths are prescription medicines.

Footnotes

CAS Number:

Budesonide: 51333-22-3

Formoterol: 183814-30-4

Alternative names

Budesonide: 16α, 17α-22 R, S-propylmethylenedioxypregna-1, 4-diene-1β, 21-diol-3, 20-dione

Formoterol: (R*R*)-(±)-N-[2-hydroxy-5-[1-hydroxy-2-[[2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]formamide, (E)-2-butendioate(2:1), dihydrate

Applicant

Private applicant

Current scheduling

Budesonide

Schedule 4

BUDESONIDE except when included in Schedule 2.

Schedule 2

BUDESONIDE in aqueous nasal sprays delivering 64 micrograms or less of budesonide per actuation when the maximum recommended daily dose is no greater than 400 micrograms, for the prophylaxis or treatment of allergic rhinitis for up to 6 months in adults and children 12 years of age and over.

Index

BUDESONIDE

Schedule 4
Schedule 2

Formoterol

Schedule 4

FORMOTEROL

Index

FORMOTEROL

Schedule 4

Proposed scheduling

A request has been made to amend the Poisons Standard as follows:

Budesonide

Schedule 4 - Amend Entry

BUDESONIDE except when included in Schedule 2 or Schedule 3.

Schedule 3 - New Entry

BUDESONIDE when combined with formoterol in a:

  1. dry powder inhaler delivering 160 micrograms budesonide and 4.5 micrograms formoterol fumarate dihydrate per inhalation (delivered dose) or less, when packed in a primary pack containing 60 inhalations or less; or
  2. pressurised metered dose inhaler delivering 80 micrograms budesonide and 2.25 micrograms formoterol fumarate dihydrate per actuation (delivered dose) or less, when packed in a primary pack containing 120 actuations or less; and

where supply is limited:

  1. to persons aged 12 years and over with evidence of medically diagnosed asthma; and
  2. for use as an anti-inflammatory reliever.
Appendix F, Part 3 - New Entry
Poison Warning statements Safety direction
Budesonide when included in Schedule 3. 32 (This preparation should be part of an overall treatment plan regularly assessed with your doctor.)

Appendix M - New Entry

BUDESONIDE when combined with formoterol, where the pharmacist providing professional advice:

  • Demonstrates competencies as outlined in the Pharmaceutical Society of Australia competency-based education framework relevant to the supply of budesonide/formoterol as a Pharmacist Only medicine; and
  • Complies in all respects with the relevant professional practice standards, and the Pharmaceutical Society of Australia professional practice guidance for supply of budesonide/formoterol as a Pharmacist Only medicine; and
  • Confirms the patient has a medical diagnosis of asthma; and
  • Documents the supply of budesonide/formoterol in a clinical information system in accordance with professional practice guidance.

Index - Amend Entry

BUDESONIDE

Schedule 4
Schedule 3
Schedule 2
Appendix F, Part 3
Appendix M

Formoterol

Schedule 4 - Amend entry

FORMOTEROL except when included in Schedule 3.

Schedule 3 - New Entry

FORMOTEROL when combined with budesonide in a:

  1. dry powder inhaler delivering 160 micrograms budesonide and 4.5 micrograms formoterol fumarate dihydrate per inhalation (delivered dose) or less, when packed in a primary pack containing 60 inhalations or less; or
  2. pressurised metered dose inhaler delivering 80 micrograms budesonide and 2.25 micrograms formoterol fumarate dihydrate per actuation (delivered dose) or less, when packed in a primary pack containing 120 actuations or less; and

when supply is limited:

  1. to persons aged 12 years and over with evidence of medically diagnosed asthma; and
  2. for use as an anti-inflammatory reliever.
Appendix F, Part 3 - New Entry
Poison Warning statements Safety direction
Formoterol when included in Schedule 3. 32 (This preparation should be part of an overall treatment plan regularly assessed with your doctor.)

Appendix M - New Entry

Formoterol when combined with budesonide, where the pharmacist providing professional advice:

  • Demonstrates competencies as outlined in the Pharmaceutical Society of Australia competency-based education framework relevant to the supply of budesonide/formoterol as a Pharmacist Only medicine; and
  • Complies in all respects with the relevant professional practice standards, and the Pharmaceutical Society of Australia professional practice guidance for supply of budesonide/formoterol as a Pharmacist Only medicine; and
  • Confirms the patient has a medical diagnosis of asthma; and
  • Documents the supply of budesonide/formoterol in a clinical information system in accordance with professional practice guidance.

Index - Amend Entry

FORMOTEROL

Schedule 4
Schedule 3
Appendix F, Part 3
Appendix M

Key uses / expected use

Medicines

Reasons for proposal put forward by the applicant

Budesonide/formoterol fix dose combination (FDC) for 'as needed' use is well-established and is a recommended alternative reliever therapy option in the Australian asthma guidelines for Steps 2-4. Rescheduling to allow access to patients as a Pharmacist Only Medicine would provide the following benefits:

  • Budesonide/formoterol FDC 'as needed' provides a more effective anti-inflammatory reliever alternative to the current OTC reliever which many patients now over rely on as their main treatment option thus helping to reshape behaviour learned over many years. In more recently diagnosed patients, this will also help to avoid the establishment of patient reliance on short acting β-agonist (SABA).
  • OTC budesonide/formoterol FDC 'as needed' will provide patients with earlier inhaled corticosteroid (ICS) therapy helping to address the underlying inflammation to prevent exacerbations or asthma deterioration. ICS adherence is also not a concern with this therapy as the budesonide is provided in combination with the reliever.
  • The benefits of reducing SABA overreliance and ICS under-utilisation would have indirect benefits with fewer patients with uncontrolled or poorly-controlled asthma, reduced urgent asthma-related healthcare visits and potentially less asthma-related deaths. Thus minimising cost and risk to the community.
  • Consultations between pharmacists and patients with asthma will have an increased focus on the importance of reduction in underlying inflammation (in addition to symptom relief) to prevent exacerbations and maintain control. This has the potential to improve asthma outcomes for all patients, not only those who are recommended OTC budesonide/formoterol FDC.
  • With patient consent and in accordance with professional practice guidance, pharmacists will follow up with the patient's medical practitioner as appropriate about the supply of OTC budesonide/formoterol FDC. This will facilitate best practice communication and collaboration between the pharmacist and medical practitioner about the patient's ongoing asthma management. This is especially important for patients with mild asthma.

Australian regulations

  • According to the TGA Ingredient Database[35], budesonide is:
    • Available for use as an active ingredient in biologicals, export only, over the counter and prescription medicines;
    • Available for use as an excipient ingredient in biologicals, devices and prescription medicines;
    • Not available as an equivalent ingredient in any application.
  • According to the TGA Ingredient Database[36], formoterol is:
    • Available for use as an active ingredient in biologicals, export only and prescription medicines;
    • Available for use as an excipient ingredient in biologicals, devices and prescription medicines;
    • Not available as an equivalent ingredient in any application.
  • As of August 2020, there were 43 medicines currently active on the Australian Register of Therapeutic Goods (ARTG)[37] that contain budesonide as an active ingredient. These include 27 prescription medicines, 8 non-prescription medicines and 8 export only medicines.
  • As of August 2020, there were 27 medicines currently active on the Australian Register of Therapeutic Goods (ARTG)[38] that contain formoterol as an active ingredient. These include 27 prescription medicines.
  • As of August 2020, there were 14 medicines currently active on the Australian Register of Therapeutic Goods (ARTG)[39] that contain budesonide+formoterol as active ingredients. These include 14 prescription medicines.
  • Budesonide and formoterol are not permitted to be included in listed medicines as they are not included in the Therapeutic Goods (Permissible Ingredients) Determination[40] No.2 of 2020.
  • The TGA prescribing medicines in pregnancy database[41] classifies budesonide and formoterol as:
    Drug name Category Classification Level 1 Classification Level 2 Classification Level 3
    Budesonide A Endocrine system Corticosteroids Inhalation/intranasal
    Budesonide A Respiratory System Inhalational agents Preventative aerosols and inhalations
    Budesonide (systemic) B3 Alimentary System Antidiarrhoeals
    Formoterol B3 Respiratory System Inhalational agents Bronchospasm relaxants

    Category A - Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the foetus having been observed.

    Category B3 - Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed.

    Studies in animals have shown evidence of an increased occurrence of foetal damage, the significance of which is considered uncertain in humans.

  • There are no warning statements pertaining to budesonide and formoterol in the Therapeutic Goods (Medicines Advisory Statements) Specification 2019[42].
  • As of August 2020, there were 240 reports of adverse events for products containing budesonide+formoterol as active ingredients on the Database of Adverse Event Notifications (DAEN)[43], with 140 reports where budesonide+formoterol were the single suspected medicine.
  • As of August 2020, there were three products containing budesonide listed on the Public Chemical Registration Information System Search (PubCRIS)[44].

International regulations


CAS Number:

620-52-2

Alternative names

[3-(2-dimethylaminoethyl)-1H-indol-4-yl] dihydrogen phosphate

Applicant

Private applicant

Current scheduling

Schedule 9

PSILOCYBINE.

Index

PSILOCYBINE

Schedule 9

Proposed scheduling

A request has been made to amend the Poisons Standard as follows:

Schedule 9 - Amend entry

PSILOCYBINE except when included in Schedule 8.

Schedule 8 - New Entry

PSILOCYBIN for use in the treatment of medical conditions:

  1. In preparation for oral use as part of psychotherapy under the authorisation of a treating psychiatrist or specialist addiction physician in a medically controlled environment;
  2. Manufactured in accordance with the Narcotic Drugs Act 1967; and/or
  3. Imported or manufactured in Australia as therapeutic goods, or for use in therapeutic goods, for supply, in accordance with the Therapeutic Goods Act 1989; and/or
  4. In therapeutic goods supplied in accordance with the Therapeutic Goods Act 1989.

Index - Amend Entry

PSILOCYBINE

Schedule 9
Schedule 8

Key uses / expected use

Medicines

Reasons for proposal put forward by the applicant

  • This application supports the opportunity to expand the paradigm for the treatment of mental illness to improve the mental health outcomes of suffering Australians. Psilocybin has been granted two Breakthrough Therapy Designations by the Food and Drug Administration (FDA) in the United States - the first to Compass Pathways Limited in 2018 for psilocybin as part of therapy for treatment resistant depression (COMPASS, 2018) and the second in 2019 to Usona Institute for psilocybin as part of therapy in the treatment of major depressive disorder (Businesswire, 2019). This designation from the FDA acknowledges both the unmet medical need in these broad populations and the potential for these therapies to offer significant improvements over existing therapies.
  • In a medically controlled environment psilocybin-assisted therapy is safe, non-addictive, and there is no increase in risk for mental ill-health in a clinically controlled environment (Passie, 2008).
  • Psilocybin-assisted therapy has yielded remarkable clinical results for depression and anxiety in numerous trials at leading universities internationally (Johnson & Griffiths, 2017).
  • Psilocybin-assisted therapy can lead to remission in 60-80% of cases of anxiety and depression, whereas current existing treatments lead to remission in a maximum of 35-42% of cases (Griffiths et al., 2016; Ross, 2016; Carhart-Harris, 2016).
  • The rescheduling of psilocybin from Schedule 9 to Schedule 8 will make it easier for Australians suffering from depression and anxiety disorders and substance abuse (and potentially other illnesses such as anorexia nervosa and OCD) to access psilocybin-assisted therapy through their psychiatrists and specialist addiction physicians (with supporting therapists) in strictly medically controlled environments. It will also increase the ease and reduce costs of clinical research.

Australian regulations

International regulations


Footnotes

CAS Number:

42542-10-9

Alternative names

IUPAC Name: 1-(1,3-benzodioxol-5-yl)-N-methylpropan-2-amine

Methylenedioxymethamphetamine

α-Dimethyl-3,4-(Methylenedioxy)Phenylethylamine

3,4-Methylenedioxy-N-Α-Dimethylphenylethylamine

Applicant

Private applicant

Current scheduling

MDMA is currently in Schedule 9 of the Poisons Standard as follows:

Schedule 9

N, α-DIMETHYL-3,4-(METHYLENEDIOXY)PHENYLETHYLAMINE *(MDMA).

Index

N, α-DIMETHYL-3,4-(METHYLENEDIOXY)PHENYLETHYLAMINE
cross reference: 3,4-METHYLENEDIOXY-N-α-DIMETHYLPHENYLETHYLAMINE, MDMA

Proposed scheduling

A request has been made to amend the Poisons Standard as follows:

Schedule 9 - Amend Entry

N, α-DIMETHYL-3,4-(METHYLENEDIOXY)PHENYLETHYLAMINE *(MDMA) except when in Schedule 8.

Schedule 8 - New Entry

N, α-DIMETHYL-3,4-(METHYLENEDIOXY)PHENYLETHYLAMINE *(MDMA) for use in the treatment of medical conditions:

  1. In preparation for oral use under the authorisation of a treating psychiatrist or addiction specialist physician in a medically controlled environment;
  2. Manufactured in accordance with the Narcotic Drugs Act 1967; and/or
  3. Imported or manufactured in Australia as therapeutic goods, or for use in therapeutic goods, for supply, in accordance with the Therapeutic Goods ct 1989; and/or
  4. In therapeutic goods supplied in accordance with the Therapeutic Goods Act 1989.

Index - Amend Entry

N, α-DIMETHYL-3,4-(METHYLENEDIOXY)PHENYLETHYLAMINE
cross reference: 3,4-METHYLENEDIOXY-N-α-DIMETHYLPHENYLETHYLAMINE, MDMA

Schedule 9
Schedule 8

Key uses / expected use

Medicines

Reasons for proposal put forward by the applicant

  • In a controlled setting, MDMA-assisted psychotherapy supports patients in reprocessing traumatic and painful memories, making MDMA efficacious for treating PTSD and addictions associated with trauma (Feduccia & Mithoefer, 2018)[60].
  • There is strong evidence for the safety and efficacy of MDMA-assisted psychotherapy for the treatment of PTSD (Bahji et al, 2020)[61]. In controlled settings there have been no major adverse events and minor side effects related to MDMA resolve within a few days (MAPS, 2019)[62]. Further, medicinal MDMA does not produce dependence as defined in the contemporary versions of the Diagnostic and Statistical Manual of Mental Disorders or the International Statistical Classification of Diseases (Kalant, 2001)[63].
  • MDMA-assisted therapy has been granted 'Breakthrough Therapy' status by the US Food and Drug Administration (FDA), expediting its transition to prescription medicines subject to positive outcomes from current Phase 3 trials (MAPS PR, 2017)[64]. This designation highlights the FDA's anticipation that MDMA-assisted therapies may offer substantial advantage over current treatments.
  • The FDA has approved an "Expanded Access" or "Compassionate Use" scheme using MDMA for PTSD in patients who have limited treatment options (MAPS PR1, 2020)[65]. Israel launched a Compassionate Use program for MDMA-assisted therapy for PTSD in 2019 (MAPS PR2, 2020)[66] and Switzerland also has a compassionate use program for MDMA with individual authorisations by the Federal Office of Public Health (Sessa et al, 2019)[67]. Recently, the Australian Therapeutic Goods Administration (TGA) approved the first application for the use of MDMA-assisted therapy for the treatment of a patient with treatment resistant PTSD under the Special Access Scheme-B.
  • MDMA treatment is only to be used in clinical settings according to the guidelines of a Schedule 8 controlled substance in the Poisons Standards and in accordance with strict safety protocols for supplying MDMA-assisted therapy through health care providers in a medically controlled environment.
  • The current Schedule 9 classification of MDMA places hurdles on research (cost, stigma and ease of access) and on its use in a medically controlled environment as part of evidence-based treatment. Reclassifying MDMA as a Schedule 8 substance will reduce cost and improve ease of access for researchers and specialist medical practitioners for treatment of individuals seeking relief for treatment resistant conditions via the Special Access Scheme.
  • Given the demonstrated therapeutic benefits for individuals suffering from PTSD whose condition has not improved after standard forms of treatment and, high remission rates shown in clinical trials, it is apparent that MDMA used in a medically controlled environment does not fit within the requirements of a Schedule 9 Substance and more closely reflects the requirements of Schedule 8.

Australian regulations

International regulations


Footnotes

2 Proposed amendments referred for scheduling advice to ACCS #9

CAS Number:

131860-33-8

Alternative names

Methyl (E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yl]oxyphenyl]-3-methoxyprop-2-enoate (IUPAC name)

Applicant

Australian Pesticides and Veterinary Medicines Authority (APVMA)

Current scheduling

Substance is currently listed in Schedules 5 of the Poisons Standard as follows:

Schedule 5

AZOXYSTROBIN

Index

AZOXYSTROBIN

Proposed scheduling

Schedule 5 - Amend Entry

AZOXYSTROBIN except in suspension concentrate preparations containing 10 per cent or less azoxystrobin.

Key uses / expected use

Agriculture, pesticide formulations, to treat a variety of fungal diseases.

Reasons for proposal put forward by the applicant

  • The proposal is to amend the Schedule 5 entry for azoxystrobin to include a cut-off for preparations containing 10 per cent or less of azoxystrobin, used for control of a variety of fungal diseases in turf.
  • The applicant proposes that, the inclusion of an exemption to unscheduled formulations containing 10 per cent or less of azoxystrobin, will provide an additional choice of available products to consumers.
  • In acute toxicity studies in rats, 10 per cent azoxystrobin was of low acute oral toxicity and dermal toxicity. Azoxystrobin was a slight skin and eye irritant in rabbits, but was not a skin sensitiser in guinea pigs (maximisation test).
  • The cut off of 10 per cent or less is considered to be supported by the data evaluated by the APVMA, based on the testing results from formulations containing 96g/L of azoxystrobin and 194 g/L triticonazole.
  • International restrictions.
    • EU acceptable minimum residue levels (MRL) in or on food and feed of plant and animal origin are between 1x10-7 to 0.007%[80].

Australian regulations

International regulations

Footnotes

CAS Number:

131986-72-7

Alternative names

(RS)-(E)-5-(4-chlorobenzylidene)-2,2-dimethyl-1-(1H-1,2,4-triazol-1-ylmethyl) cyclopentanol (IUPAC name)

Applicant

Australian Pesticides and Veterinary Medicines Authority (APVMA)

Current scheduling

Substance is currently listed in Schedules 5 of the Poisons Standard as follows:

Schedule 5

TRITICONAZOLE

Index

TRITICONAZOLE

Schedule 5

Proposed scheduling

Schedule 5 - Amend Entry

TRITICONAZOLE except in suspension concentrate preparations containing 20 per cent or less triticonazole.

Key uses / expected use

Agriculture, pesticide formulations, to treat a variety of fungal diseases.

Reasons for proposal put forward by the applicant

  • The proposal is to amend the Schedule 5 entry for triticonazole to include a cut-off for preparations containing 20 per cent or less of triticonazole used for control of a variety of fungal diseases in turf.
  • The applicant proposes that, the inclusion of an exemption to unscheduled formulations containing 20 per cent or less of triticonazole, will provide an additional choice of available products to consumers.
  • In acute toxicity studies in rats, 20 percent triticonazole was of low acute oral toxicity and dermal toxicity. Triticonazole was a slight skin and eye irritant in rabbits, but was not a skin sensitiser in guinea pigs (maximisation test).
  • The cut off of 20 per cent or less is considered to be supported by the data evaluated by the APVMA, based on the testing results from formulations containing 96g/L of Azoxystrobin (~10 per cent) and 194 g/L Triticonazole (~20 per cent).
  • International restrictions.
    • EU acceptable minimum residue levels (MRL) in or on food and feed of plant and animal origin is 1x10-7 %[92].

Australian regulations

International regulations

Footnotes

3 Proposed amendments referred for scheduling advice to the Joint ACMS-ACCS #26

CAS Number:

123-99-9

Alternative names

Nonanedioic acid

Applicant

Private applicant

Current scheduling

Azelaic acid is currently in Schedules 2 and 4 of the Poisons Standard as follows:

Schedule 4

Azelaic acid except:

  1. When included in Schedule 2; or
  2. In preparations containing 1 per cent or less of azelaic acid for non-human use.

Schedule 2

AZELAIC ACID in dermal preparations.

Index

AZELAIC ACID

Schedule 4
Schedule 2

Proposed scheduling

A request has been made to amend the Poisons Standard as follows:

Schedule 5 - New Entry

Azelaic acid for human therapeutic or cosmetic use, except in preparations for topical use containing 10 per cent or less of azelaic acid.

Schedule 4 - Amend Entry

Azelaic acid except:

  1. when included in Schedule 5 or Schedule 2; or
  2. in preparations containing 1 per cent or less of azelaic acid for non-human use.

Schedule 2 - Delete Entry

AZELAIC ACID in dermal preparations.

Index

AZELAIC ACID

Schedule 5
Schedule 4
Schedule 2

Key uses / expected use

Medicines, cosmetic, industrial use etc.

Reasons for proposal put forward by the applicant

  • Azelaic acid is a naturally occurring dicarboxylic acid produced by Malassezia furfur and found in whole grain cereals, rye, barley and animal products. Azelaic acid possesses antibacterial, keratolytic, comedolytic, and antioxidant activity. Azelaic acid is bactericidal against Propionibacterium acnes and Staphylococcus epidermidis due to its inhibitory effect on the synthesis of microbial cellular proteins. Azelaic acid also possesses a direct anti-inflammatory effect due to its scavenger activity of free oxygen radical.
  • It is used topically to reduce inflammation associated with acne and rosacea.
  • A change in scheduling would allow Australian producers to benefit from sales of a more superior ingredient in their product(s), since it is widely used in the UK, US and EU in cosmetic and cosmeceuticals as a functional buffer and masking ingredient, but also has additional performance benefits for the consumer.
  • Azelaic acid is found in products sold over the counter in Australia and online by US, UK and EU brands. These brands are able to formulate products using azelaic acid in their cosmetic creams however, Australian producers are not allowed to use azelaic acid in cosmetics and cosmeceuticals.
  • Cosmetic chemists can make products using other acids such as lactic acid, salicylic acid, glycolic acid, mandelic acid, tartaric acid, citric acid, ascorbic acid. Azelaic acid use in cosmetics and cosmeceutical products should also be permitted as it is beneficial rather than harmful having excellent anti-inflammatory properties, making it a superior acid choice for use in skincare products.

Australian regulations

International regulations


Footnotes

CAS Number:

868-77-9

Alternative names

2-hydroxyethyl methacrylate, ethylene glycol mono methacrylate, HEMA

Applicant

Private applicant

Current scheduling

Hydroxethyl methacrylate is currently in Schedule 5 of the Poisons Standard as follows:

Schedule 5

2-HYDROXYETHYL METHACRYLATE except when included in dental restorative preparations for therapeutic use or in nail preparations when labelled "Avoid contact with skin".

Appendix E, Part 2

2-HYDROXYETHYL METHACRYLATE

Poison Standard Statements
2-HYDROXYETHYL METHACRYLATE

A (For advice, contact a Poisons Information Centre (e.g. phone Australia 13 11 26; New Zealand 0800 764 766) or a doctor (at once)). E1 (If in eyes wash out immediately with water.), S1 (If skin or hair contact occurs, remove contaminated clothing and flush skin and hair with running water.)

Appendix F, Part 3
Poison Warning Statements Safety Direction
2-HYDROXYETHYL METHACRYLATE 28 ((Over) (Repeated) exposure may cause sensitisation 4 (Avoid contact with skin.)

Index

2-HYDROXYETHYL METHACRYLATE

Schedule 5
Appendix E, Part 2
Appendix F, Part 3

Proposed scheduling

A request has been made to amend the Schedule 5 entry in the Poisons Standard as follows:

Schedule 5 - Amended entry

2-HYDROXYETHYL METHACRYLATE except:

  1. when included in dental restorative preparations for therapeutic use or in nail preparations when labelled "Avoid contact with skin"; or
  2. in other preparations not for human therapeutic or cosmetic use containing 1 per cent or less of 2-hydroxyethyl methacrylate.

Key uses / expected use

Cosmetic, domestic, commercial, medical devices etc.

Reasons for proposal put forward by the applicant

  • 2-hydroxethyl methacrylate is not hazardous to human health at low concentrations in preparations that are not cosmetics or for therapeutic use. It is proposed that a lower limit be added consistent with the entries for methyl- and ethyl-methacrylate to support the supply of products containing the substance at low concentrations without warnings that imply a hazard that does not exist.
  • Methyl- and ethyl-methacrylate are listed in Schedules 6 and 5 respectively for preparations containing more than 1 per cent of the substances. However, the lack of a lower limit in the listing for 2-hydroxyethyl methacrylate makes this listing more onerous than those for the related substances that have been acknowledged to be more toxic.
  • The proposed change is not expected to have any impact to public health as concentration of 2-hydroxyethyl methacrylate of less than 1 per cent would not cause the preparation in which it is included to be considered hazardous. The change would allow the substance to be used in non-cosmetic and non-therapeutic preparations at low concentrations without precautionary warnings.
  • There has been no change in opinion on the toxicity and safety of the substance since it was first considered for scheduling in 2014. The reason for this application is that the listing didn't consider the use of the substance at low concentrations in preparations that are not cosmetics or medicines.
  • Noting the delegate's expressed concern with the 'potential use in other product at high concentrations' in the 2015 decision, the NICNAS IMAP human health Tier II assessment and use of 2-Hydroxyethyl Methacrylate at very low concentrations in certain consumer products, it is appropriate to introduce a lower limit for the Schedule entry for 2-hydroxyethyl methacrylate in line with those for methyl- and ethyl-methacrylate.

Australian regulations

International regulations

  • The European Chemicals Agency (ECHA)[123] hazard classification for 2-hydroxyethyl methacrylate is, 'Warning! According to the harmonised classification and labelling (CLP00) approved by the European Union, this substance causes serious eye irritation, causes skin irritation and may cause an allergic skin reaction.'
  • A 2005 Cosmetic Ingredient Review (CIR) report concluded that methyacrylate ester monomers are safe to use in nail enhancement products when skin contact is avoided. Products containing these ingredients should be accompanied with directions to avoid skin contact, because of the sensitising potential of methacrylates' (CIR, 2005).[120]
  • 2-hydroxyethyl methacrylate is not listed on the European Commission database for information on cosmetic substances and ingredients database (CosIng)[125].
  • In New Zealand, there is an entry for 2-hydroxyethyl methacrylate on the New Zealand Inventory of Chemicals (NZIoC)[126] (added Dec 2006).

Footnotes

CAS Number:

1309-42-8

Alternative names

Dihydroxy magnesium

Applicant

The Australian Pesticides and Veterinary Medicines Authority (APVMA)

Current scheduling

Magnesium hydroxide is not included in the Poisons Standard.

Proposed scheduling

A request has been made to formally exclude magnesium hydroxide from Scheduling via inclusion in Appendix B.

Key uses / expected use

Pesticide formulation, medicines and medical devices.

Reasons for proposal put forward by the applicant

  • APVMA has received an application for registration of an insecticide product containing 60% magnesium hydroxide (as active constituent) in a suspension concentrate formulation for use as an insecticide to control whiteflies, mites, thrips and aphids in vegetable crops.
  • Magnesium hydroxide is an inorganic compound with the formulation Mg(OH)2. It occurs naturally in the environment as the mineral 'brucite'. It has many uses including: flame retardants, antiperspirant/deodorant, wastewater treatment, food additive (E528) and in human medicines, orally as an antacid, laxative and tocolytic and dermally for the topical treatment for canker sores.
  • Although magnesium hydroxide is an ingredient in a number of veterinary feed additives, it has not been approved by APVMA as an active constituent or listed in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP). The ubiquitous use of magnesium hydroxide under therapeutic conditions, with direct oral and skin exposure, indicate it to be a substance of low toxicological concern and sufficient toxicological data are available to recommend a scheduling decision.
  • Magnesium hydroxide is of low oral, dermal and inhalation toxicity and is not an eye or skin irritant or sensitiser. Evidence indicates magnesium salts are neither genotoxic nor carcinogenic and have no effects on fertility, reproduction and development. Observed adverse effects from repeated exposure to high doses are due to an electrolyte imbalance manifested by increased Mg2+ /Ca2+ blood level ratios. Effects are reversible on cessation of exposure. Exposure to hazardous levels of magnesium hydroxide is unlikely to occur from its use as pesticide. Risks are manageable from appropriate product labelling and adherence to safety directions.
  • For the purpose of its use as an active ingredient in agricultural pesticides and/or veterinary feed products, APVMA propose that, based on its toxicological profile, magnesium hydroxide be exempt from Scheduling.

Australian regulations

  • According to the TGA Ingredient Database[127],
    • Magnesium hydroxide is available for use as an active and excipient ingredient in biologicals, export only, listed medicines, over the counter, prescription medicines and as an excipient in devices. It is not available as a homoeopathic ingredient in listed medicines nor as an equivalent ingredient in any application.
    • Aluminium magnesium hydroxide carbonate is available for use as an excipient ingredient in prescription medicines and is not available as an active or equivalent ingredient in any application.
  • As of August 2020, there were 74 medicines currently active on the Australian Register of Therapeutic Goods (ARTG)[128] that contain magnesium hydroxide as an active ingredient. These include 13 non-prescription medicines, 59 listed medicines, one medical device and one export only medicine.
  • According to the Therapeutic Goods (Permissible Ingredients) Determination[129] No.3 of 2020, magnesium hydroxide is permitted to be included in listed medicines as follows:
    Item Ingredient name Purpose Specific requirements
    3141 MAGNESIUM HYDROXIDE A, E

    When used as an active ingredient, can only be supplied as an uncompounded medicine substance packed for retail sale, and must comply with an uncompounded substance monograph of the British Pharmacopoeia, as in force or existing from time to time.

    When the medicine is not promoted or marketed as laxative, contains more than 2 g magnesium hydroxide per maximum recommended daily dose, the following warning statements are required on the label:

    • (LAX5) 'This product contains [name of the herb(s) or the chemical component(s)]'
    • (LAX4) 'This product may have laxative effect'.

    A = active ingredient for a medicine has the same meaning as in the Regulations
    E = excipient for a medicine meaning an ingredient that is not an active ingredient or a homoeopathic preparation ingredient

  • Magnesium hydroxide is not included in the TGA prescribing medicines in pregnancy database[130].
  • There are no warning statements pertaining magnesium hydroxide in the Therapeutic Goods (Medicines Advisory Statements) Specification 2019[131].
  • As of May 2020, there were 138 reports of adverse events for products containing sodium hydroxide as an active ingredient on the Database of Adverse Event Notifications (DAEN),[132] with 38 reports where magnesium hydroxide was the single suspected medicine.
  • As of August 2020 there were three animal treatment products containing magnesium hydroxide listed on the Public Chemical Registration Information System Search (PubCRIS).[133]
  • In 2009-2019 there were no adverse events recorded for magnesium hydroxide in the APVMA Adverse Experience Reporting Program database (AERP)[134].

International regulations


CAS Number:

97-99-4

Alternative names

Oxolan-2ylmethanol, Tetrahydrofuran-2-yl methanol

Applicant

Australian Pesticides and Veterinary Medicines Authority (APVMA)

Current scheduling

THFA is not currently included in the Poisons Standard.

Proposed scheduling

A request has been made to include THFA in the Poisons Standard as follows:

Schedule 6 - New Entry

TETRAHYDROFURFURYL ALCOHOL, excluding its derivatives.

Key uses / expected use

Cosmetic, agriculture, industrial use, medicines

Reasons for proposal put forward by the applicant

  • THFA is approved as an industrial chemical. It is used as a solvent in certain agricultural chemicals. As it is currently unscheduled, it does not need to be declared on the product label. Based on the assessment of new agricultural chemicals, the presence of THFA in the formulation is identified during assessment, and suitable product-based safety directions are recommended. However, as the solvent is not declared on the label, there can be challenges for industry and end users in determining the justification for warning statements and personal protective equipment. The inclusion of THFA in a Schedule of the Poisons Standard, with the accompanying requirement to declare it on the label, would assist in this risk communication.
  • Internationally, reported uses of THFA in cosmetics include uses as a fragrance ingredient, as a masking agent and as a solvent for nail cleaning products. Commercial uses which have been reported for THFA include use as an adhesive agent or sealant in general manufacturing, as a fuel additive and as a solvent. It forms an intermediate in the production of certain fungicides and pharmaceuticals. It is used as a solvent in a limited number of emulsifiable concentration formulations of agvet products. This last use is anticipated to represent the only likely use with major public exposure, however it is noted that all of the currently registered products are intended for commercial use, without home garden applications.
  • THFA is classified as hazardous in the Hazardous Chemical Information System (HCIS) (Safe Work Australia), based on serious eye irritation and reproductive toxicity.

Australian regulations

According to the TGA Ingredient Database[138], THFA is:

International regulations


4 Enquiries

Any questions relating to submissions should be directed by email to medicines.scheduling@health.gov.au (for substances referred to the ACMS or Joint ACCS-ACMS) or chemicals.scheduling@health.gov.au (for substances referred to the ACCS).