1.2. Interim decision in relation to 1,4-Dimethylpentylamine (DMPA)

1. Interim decisions on proposed amendments referred to the Advisory Committee on Medicines Scheduling (ACMS #27, June 2019)

Interim decision in relation to 1,4-Dimethylpentylamine (DMPA)

Interim decision

Pursuant to regulation 42ZCZN of the Regulations, a Delegate of the Secretary has, in relation to the proposed amendment, made an interim decision to amend the current Poisons Standard in relation to 1,4-dimethylpentylamine (DMPA) as follows:

Proposed date of effect of the proposed amendment

1 February 2020

Reasons for the interim decision (including findings on material questions of fact)

In this section: Applicant's scheduling proposal and reasons for the proposal | Current scheduling status | Scheduling history | Australian regulations | International regulations | Substance summary | Summary of pre-meeting public submissions | Summary of ACMS advice/recommendations to the Delegate | Delegate's considerations | Reasons for the interim decision

Applicant's scheduling proposal and reasons for the proposal

An application to create a Schedule 10 entry for DMPA was considered.

The Applicant's proposed amendments to the Poisons Standard were:

The Applicant's main points provided in support of the proposed amendments were as follows:

• 1,4-Dimethylpentylamine (DMPA) is currently captured under the Schedule 10 entry for 'Alkylamines with stimulant properties' due to its similarities to 1,3-dimethylamylamine (DMAA) and 1,3-dimethylbutylamine (DMBA).
• In order to remove any potential ambiguity about the scheduling status of DMPA, it is proposed that a new Schedule 10 entry be created for DMPA. This would characterise DMPA as a substance of such danger to health as to warrant prohibition of sale, supply and use.

Current scheduling status

DMPA is not specifically scheduled in the current Poisons Standard. However, the related substances alkylamines (group entry), 1,3-dimethylamylamine (DMAA) and 1,3-dimethylbutylamine (DMBA) are in the current Poisons Standard as follows:

Alkylamines with stimulant properties

1,3-dimethylamylamine (DMAA)

1,3-dimethylbutylamine (DMBA)

Scheduling history

DMPA has not been previously considered for scheduling; therefore a scheduling history is not available.

DMAA

In August 2012, the ACMS considered a delegate-initiated proposal to list DMAA in Schedule 9 of the Poisons Standard following New Zealand's temporary Class Drug Notice of 8 March 2012 advising that DMAA would be classified as a temporary class drug (equivalent to Schedule 9). New Zealand's temporary prohibition of DMAA came into effect on 9 April 2012.

The ACMS noted that there was inadequate evidence to suggest DMAA's toxicological and pharmacological properties to warrant a Schedule 9 listing. DMAA was not listed in either Schedule IV to the United Nations Convention on Narcotic Drugs, 1961 or in Schedule 1 of the United Nations Convention on Psychotropic Substances, 1971. There was a lack of supporting evidence to reach the conclusion that DMAA needs the same level of control as amphetamine. At the time, DMAA's toxicological properties met the Appendix C (now Schedule 10) scheduling criteria. The Committee recommended that DMAA be placed in Appendix C (now Schedule 10) as a result of:

• The absence of an accepted therapeutic use;
• The stimulant effect that can induce a psychoactive effect;
• Its active promotion as a party drug and as a sports supplement;
• The lack of evidence of dependence;
• The significant number of adverse events including cardiac, nervous and psychiatric disorders that have been reported with use of DMAA including cerebral haemorrhage and heart attacks; and
• The high potential for misuse and abuse.

Based on DMAA's toxicity, lack of data supporting long-term safety, wide variability in potency of different doses of DMAA and the high risk of use, misuse and illicit use, the Delegate agreed with the Committee and placed DMAA in Schedule 10 effective on 8 August 2012.^[5]

DMBA and alkylamines

In June 2017, following a recommendation from the ACMS, the Delegate made a final decision to create new entries for DMBA and other alkylamines with stimulant properties including 1,5-dimethylhexylamine (DMHA) in Schedule 10. The decision was based on the structural similarity of DMBA with DMAA, which was previously included in Schedule 10 of the Poisons Standard. DMBA was readily available in Australia, despite lack of proof of efficacy and safety and accepted therapeutic use. DMBA is also listed by the Australian Sports Anti-doping Authority (ASADA) and the World Anti-Doping Authority (WADA). WADA considers DMBA to be a health risk due to little pharmacological data of its effects in humans and as it is a non-approved drug. The potential for misuse and abuse was considered high.

Australian regulations

• DMPA is not listed on the TGA Ingredient Database.
• There are no medicines currently active on the Australian Register of Therapeutic Goods (ARTG)1 that contain DMPA as an active ingredient.
• DMPA is not permitted to be included in listed medicines as it is not included in the Therapeutic Goods (Permissible Ingredients) Determination No. 2 of 2019.^[6]
• The Database of Adverse Event Notifications (DAEN)^[7] contains no reports of adverse events for products containing DMPA as an active ingredient.
• There are no products containing DMPA listed on the Public Chemical Registration Information System Search (PUBCRIS).^[8]

International regulations

• The European Chemicals Agency (ECHA) hazard classification for DMPA is, 'Danger! According to the classification provided by companies to ECHA in CLP notifications this substance causes severe skin burns and eye damage and is a flammable liquid and vapour'.
• DMPA is prohibited from sport under the World Anti-Doping Agency (WADA) List of Prohibited Substances and Methods due to its structural similarity to DMAA under category 'S6: Stimulants'.
• As DMPA is an analogue of DMAA, the regulatory status of DMAA in other jurisdictions is relevant to the scheduling application. DMAA has been banned by regulatory agencies in United States of America (USA), United Kingdom, the Netherlands and Brazil because of its links to negative health events including, strokes, heart failure and sudden death.

Substance summary

Table 1: Chemical information for 1,4-dimethylpentylamine

Property	1,4-dimethylpentylamine
Chemical structure
Molecular formula	C7H17N
Molecular weight	115.22 g/mol
CAS name	2-Amino-5-methylhexane
CAS number	28292-43-5
IUPAC and/or common and/or other names	2-hexanamine, 5-methyl-pentylamine, 1,4-dimethyl-; 1,4-dimethylamylamine; 5-methyl-2-hexylamine

Summary of pre-meeting public submissions

Two (2) submissions were received in response to the notice published under regulation 42ZCZK advising of the proposed amendment. Both were in support of the proposed amendment.

The main points in support of the proposed amendment were:

• It was noted that DMPA is currently under Schedule 10 due to its similarities to 1,3-dimethylamylamine (DMAA) and 1,3-dimethylbutylamine (DMBA). The new entry is proposed to remove any ambiguity about the scheduling of this substance.
• DMPA is prohibited by the World Anti-Doping Agency (WADA) as a stimulant.
• There has been an increase in calls to the NSW Poisons Information Centre (PIC) regarding exposures to weight-loss and body-building products in the past 5 years and most of these calls required medical attention (57%).

  Year	Calls to NSW PIC on body building/weight-loss products
  2014	57
  2015	66
  2016	68
  2017	79
  2018	59
  Jan-April 2019	30

• There is often little detail of the contents of such supplements but they commonly show signs of stimulant toxicity.
• Entry of this agent in Schedule 10 will minimise opportunity of it being included in weight loss and body building products.

Summary of ACMS advice/recommendations to the Delegate

The Committee recommended that a Schedule 10 entry for 1,4-dimethylpentylamine (DMPA) be created as follows:

The Committee also recommended an implementation date as soon as practicable.

Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the advice included:

1. risks and benefits of the use of a substance:
   • Limited research regarding the harms and possible therapeutic benefits (DMPA has never been studied in humans, presumed to pose similar risks to safety as DMBA and DMHA)
   • 1,4-dimethylpentylamine (DMPA) is covered by the Schedule 10 group entry for alkylamine with stimulant properties. It is also a structural analogue of 1,3-dimethylamylamine (DMAA) which is listed in Schedule 10 of the Poisons Standard.
   • Due to its structural similarity to DMAA and its characterization as an alkylamine with stimulant properties, DMPA has potential for harm including stroke, heart failure and sudden death.
2. the purpose for which a substance is to be used and the extent of use:
   • Nil that are currently registered, use in sports supplements, the extent of which is difficult to quantify, as often products are not accurately labelled.
3. the toxicity of a substance:
   • As established for alkylamines with stimulant properties; stimulant effects can induce a psychoactive effect and adverse events have been reported with use of these.
   • The potential adverse effects of alkylamines include cardiac, nervous and psychiatric disorders that have been reported with use of DMAA.
   • As an analogue of DMAA, DMPA likely has similar health risks.
4. the dosage, formulation, labelling, packaging and presentation of a substance:
   • No current registered products, or information about dosage due to a lack of human research.
5. the potential for abuse of a substance:
   • As established for alkylamines with stimulant properties.
   • Promoted for use in sports supplements to improve athletic performance and increase weight loss.
6. any other matters that the Secretary considers necessary to protect public health:
   • Broader issues around supplements also warrant consideration.
   • Communicate for clarity that 1,4-dimethylpentylamine (DMPA) is covered by the Schedule 10 group entry for alkylamine with stimulant properties.

Delegate's considerations

In making this interim decision, I have considered the following material:

• The application to amend the current Poisons Standard with respect to 1,4-dimethylpentylamine;
• Advisory Committee on Medicines Scheduling's advice;
• The public submissions received before the first closing date;
• Section 52E of the Therapeutic Goods Act 1989, in particular: (a) risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and extent of use; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health;
• The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
• The Australian Health Ministers' Advisory Council's Scheduling Handbook (V 1.0, January 2018).

Reasons for the interim decision

I agree with the Committee's finding that the relevant matters of section 52E of the Therapeutic Goods Act 1989 are: (a) the risks and benefits of the use of a substance; (b) the purposes for which a substance is to be used and the extent of use of a substance; (c) the toxicity of a substance; (d) the dosage, formulation, labelling, packaging and presentation of a substance; (e) the potential for abuse of a substance; and (f) any other matters that the Secretary considers necessary to protect public health.

In my view, the relevant parts of the Scheduling Policy Framework (SPF) 2018 are the scheduling factors for Schedule 10.

I have made the decision to amend the current Poisons Standard by creating a new Schedule 10 entry for 1,4-dimethylpentylamine (DMPA) and I have set out my reasons below.

Although DMPA is currently captured under the Schedule 10 entry for 'alkylamines with stimulant properties' it is my view that in order to reduce potential ambiguity surrounding the scheduling status of DMPA, a separate Schedule 10 entry for DMPA is appropriate. In making my decision, I have considered that DMPA is an analogue of DMAA, it is on the World Anti-Doping Agency (WADA) list of prohibited substances and that the Early Warning Advisory (EWA) of the United Nations Office on Drugs and Crime (UNODC) categorises DMPA as a stimulant, based on its structural similarity to other known substances.

In making my decision, I considered the scheduling factors for inclusion in Schedule 10, particularly 'the substance poses such a high public health risk, including potential risk, that its sale, supply and/or use require very strict control, with access generally being prohibited'. It is my view that DMPA meets the scheduling factors of Schedule 10 as the supply of DMPA to humans poses a risk due to the lack of appropriate trials in humans, lack of data on dosage and the potential for use for its psychoactive (stimulant) properties. I consider these factors to pose a significant public health risk so as to warrant prohibition by scheduling.

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