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Scheduling delegate's final decisions, March 2016

Scheduling medicines and poisons

17 March 2016

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2.6 Flubromazolam

Part A - Final decisions on matters referred to an expert advisory committee

2. Scheduling proposals referred to the November 2015 meeting of the Advisory Committee on Medicines Scheduling (ACMS#16)

2.6 Flubromazolam

Scheduling proposal

The medicines scheduling delegate has referred the following scheduling proposal for consideration by the Advisory Committee on Medicines Scheduling (ACMS):

  • To create a new entry for flubromazolam in Schedule 9 (flubromazolam is currently covered by the Schedule 4 entry for benzodiazepine derivatives).
Substance summary

The applicant has provided the following information regarding flubromazolam:

Flubromazolam is a benzodiazepine derivative. It is a triazolo analogue of the designer benzodiazepine, flubromazepam.

Benzodiazepines enhance the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. This results in anxiolytic, sedative, hypnotic, muscle relaxant and antiepileptic effects.

Molecular formula: C17H12BrFN4

CAS Number: 612526-40-6

IUPAC name: 8-bromo-6-(2-fluorphenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a]benzodiazepine.

Flubromazolam has high potency, and can cause strong sedation and amnesia at oral doses as low as 500 micrograms. Flubromazolam has an onset of effect of 30 minutes, and duration of effect of 12-18 hours. After-effects are experienced for ≥ 24 hours. There is a risk of fatal overdose if benzodiazepines such as flubromazolam are combined with other central nervous system depressants such as opioid analgesics, alcohol and 4-hydroxybutanoic acid (GHB).

There is a risk of unintended over-dosing. People who use flubromazolam for its psychoactive properties reported compulsive re-dosing. Abrupt discontinuation of flubromazolam following regular dosing over several days can result in a withdrawal phase that includes rebound symptoms such as increased anxiety and insomnia.

Flubromazolam has recently become available online (products available for sale online include the pure substance and 250 microgram pellets).

Flubromazolam has no currently established therapeutic use and is likely to present a high risk of dependency, abuse, misuse or illicit use. The dangers associated with flubromazolam are such as to warrant limiting use to strictly controlled medical and scientific research. On this basis, flubromazolam meets two of the factors for inclusion in Schedule 9 of the Poisons Standard.

Flubromazolam is a triazolo analogue of the designer benzodiazepine, flubromazepam (7- bromo-5-(2-fluorphenyl)-1,3-dihydro-1,4-benzodiazepine-2-one). Flubromazepam has a much longer time to onset of effect (4 hours) and much longer duration of effect (3 days) than flubromazolam.

Scheduling status
Flubromazolam

Flubromazolam is currently not specifically scheduled.

Flubromazolam is a benzodiazepine derivative, and is therefore currently covered by the entries for 'Benzodiazepine derivatives' in Schedule 4 and Appendix D.

Schedule 4

BENZODIAZEPINE derivatives except when separately specified in these Schedules.

Appendix D

Paragraph 5 - Poisons for which possession without authority is illegal (e.g. possession other than in accordance with a legal prescription)

BENZODIAZEPINE DERIVATIVES, including those separately specified in Schedule 4 and Schedule 8.

[The additional controls on possession or supply specified in Appendix D only apply to the substances listed when included in Schedule 4 and Schedule 8.]

OTHER BENZODIAZEPINES - Specific schedule entries

Schedule 4 includes specific entries for the following benzodiazepines (in addition to the entry for benzodiazepine derivatives): bromazepam; chlordiazepoxide; clobazam; clonazepam; clorazepate; diazepam; flurazepam; ketazolam; loprazolam; lorazepam; lormetazepam; medazepam; midazolam; motrazepam; nitrazepam; oxazepam; prazepam; quazepam; temazepam; triazolam; zolazepam.

The benzodiazepines, alprazolam and flunitrazepam, are currently listed in Schedule 8.

Currently, there do not appear to be entries for any benzodiazepines in Schedule 9.

Scheduling history

FLUBROMAZOLAM

Flubromazolam has not previously been considered for scheduling.

BENZODIAZEPINES

In May 1982, the general class of benzodiazepines was included in Schedule 4. In May 1986, some individual benzodiazepine substances were listed in Schedule 4 (bromazepam, diazepam). Other individual benzodiazepine substances have subsequently been listed in Schedule 4.

National Drugs and Poisons Schedule Committee (NDPSC): February 1997; May 1997; August 1997; November 1997; February 1998

In February 1997, the NDPSC considered a proposal to include flunitrazepam in Schedule 9, in response to representations from the Chairman of the Australian Health Ministers’ Advisory Council (AHMAC). The NDPSC decided that the scheduling of flunitrazepam should be considered in May 1997. In May 1997, the NDPSC foreshadowed a Schedule 8 entry for flunitrazepam, on the basis of its abuse and the harmful effects associated with abuse. The NDPSC agreed, in August 1997, to defer further consideration until the November 1997 meeting. The NDPSC agreed, in November 1997, that there was an on-going public health issue associated with the abuse and misuse of flunitrazepam, and decided to reschedule it from Schedule 4 to Schedule 8. The NDPSC confirmed this decision in February 1998.

National Drugs and Poisons Schedule Committee (NDPSC): August 1998

The November 1997 NDPSC meeting had decided that a review of the scheduling of benzodiazepines was appropriate, following a decision to include flunitrazepam in Schedule 8, due to its known abuse and public health concerns associated with this abuse. The NDPSC considered the submissions received in response to the decision to undertake the review at its August 1998 meeting, and agreed that it was appropriate that those benzodiazepines currently included in Schedule 4 of the Standard for uniform scheduling of drugs and poisons should remain in Schedule 4.

National Drugs and Poisons Schedule Committee (NDPSC): June 2010

Delegate decision: August 2010

The NDPSC considered the scheduling of alprazolam, following a request that it be rescheduled to Schedule 8, in response to concerns about misuse and abuse. The NDPSC decided that the current scheduling of alprazolam (Schedule 4) remained appropriate. The delegate confirmed this decision in August 2010.

Advisory Committee on Medicines Scheduling (ACMS): March 2013

Delegate decision: June 2013

The ACMS considered a proposal to reschedule benzodiazepines from Schedule 4 to Schedule 8 in March 2013. The ACMS recommended that alprazolam be rescheduled from Schedule 4 to Schedule 8. The ACMS recommended that the current scheduling of other benzodiazepines remained appropriate, and that benzodiazepines should be included in Appendix D, paragraph 5.

Reasons for the recommendation to include alprazolam in Schedule 8 included public health concerns, increased morbidity and mortality in overdose, abuse and misuse (particularly in association with opioids) and evidence of widespread misuse of alprazolam.

The delegate decided to include alprazolam in Schedule 8. The delegate also decided to include a new entry in Appendix D, paragraph 5, for "Benzodiazepine derivatives, including those separately specified in Schedule 4 and Schedule 8".

Pre-meeting public submissions

No public submissions were received.

ACMS advice to the delegate

The ACMS recommended flubromazolam be included in Schedule 9.

The ACMS recommended an implementation date of 1 June 2016.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: a) the risks and benefits of the use of the substance; b) the purposes for which a substance is to be used and the extent of use of a substance; c) the toxicity of the 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 recommendation comprised the following:

  • Currently there are no established therapeutic uses for flubromazolam.
  • Flubromazolam is highly potent and causes sedation and amnesia at low doses.
  • Flubromazolam has no apparent therapeutic benefit.
  • Risks of unintentional overdose and undetected "spiking" due to very low effective dose.
  • There are reports of misuse and abuse of flubromazolam in online drug user forums.
  • There have been seizures of flubromazolam that was intended for import into South Australia.
  • Flubromazolam has no legitimate therapeutic use; used only for illicit recreational use, apparently increasing as advertising and discussed via internet.
  • Flubromazolam is similar to other benzodiazepines but very low dosages for effectiveness as well as toxicity.
  • There is a risk of fatal overdose if flubromazolam is ingested in combination with other CNS depressants such as alcohol, opioid analgesics and GHB. Users report tolerance and compulsive re-dosing.
  • There is a risk of withdrawal effects including increased anxiety and insomnia if flubromazolam is abruptly discontinued.
  • Flubromazolam is available online as pure substance or pellets and is sold via the internet as raw material and "pellets" 0.75 mg and 1.25 mg.
  • There is a risk that users will have difficulty accurately measuring the dose of flubromazolam.
  • There is a high potential for misuse and abuse of flubromazolam.
  • The low effective dose of flubromazolam could be a concern in drug facilitated crimes.
  • Unlikely that there ever will be a therapeutic use as safer benzodiazepines would be preferred.
Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACMS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors21;
  • Other relevant information.
Delegates' interim decision

The delegate's interim decision is to include Flubromazolam in Schedule 9.

The proposed implementation date is 1 June 2016.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate included: a) the risks and benefits of the use of the substance; b) the purposes for which a substance is to be used and the extent of use of a substance; c) the toxicity of the 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 recommendation comprised the following:

  • Currently there are no established therapeutic uses for flubromazolam. It is highly potent and causes sedation and amnesia at low doses. No apparent therapeutic benefit. Risks of unintentional overdose and undetected "spiking" due to very low effective dose.
  • There are reports of misuse and abuse of flubromazolam in online drug user forums. There have been seizures of flubromazolam that was intended for import into South Australia. No legitimate therapeutic use; used only for illicit recreational use, apparently increasing as advertising and discussed via internet.
  • There is a risk of fatal overdose if flubromazolam is ingested in combination with other CNS depressants such as alcohol, opioid analgesics and GHB. Users report tolerance and compulsive re-dosing. There is a risk of withdrawal effects including increased anxiety and insomnia if flubromazolam is abruptly discontinued. Similar to other benzodiazepines but very low dosages for effectiveness as well as toxicity.
  • Flubromazolam is available online as pure substance or pellets. There is a risk that users will have difficulty accurately measuring the dose of flubromazolam. There is a risk of unintended over-dosing. Sold via internet as raw material and "pellets" 0.75 mg and 1.25 mg.
  • There is a high potential for misuse and abuse of flubromazolam.
  • The low effective dose of flubromazolam could be a concern in drug facilitated crimes. Unlikely that there ever will be a therapeutic use as safer benzodiazepines would be preferred.
Delegate's consideration

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • Public submissions received;
  • ACMS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed the interim decision as no evidence has been received to alter the interim decision. The delegate has confirmed that the final decision and reasons are in keeping with those for the interim decision.

The implementation date is 1 June 2016.


Footnotes

  1. Scheduling Policy Framework for Medicines and Chemicals (SPF, 2015)

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