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Scheduling delegate's final decisions, June 2016

Scheduling of medicines and poisons

23 June 2016

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2.1 Benzodiazepine derivatives

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

2. Scheduling proposals referred to the March 2016 meeting of the Advisory Committee on Medicines Scheduling (ACMS#17)

2.1 Benzodiazepine derivatives

Referred Delegate's scheduling proposal

To delete the Schedule 4 entry of BENZODIAZEPINE DERIVATIVES and create a new Schedule 9 or Schedule 8 entry for BENZODIAZEPINE DERIVATIVES with an exception for benzodiazepines listed separately in the Schedules.

Applicant's application and scheduling proposal

Delegate-initiated application. The reason for the request was:

  • At the ACMS meeting November 2015, the Committee advised that the Schedule 4 entry of BENZODIAZEPINE DERIVATIVES be deleted and create a new entry with the same wording in Schedule 9.
Substance summary

Benzodiazepines are the major group of drugs used as anxiolytics and hypnotics, with some also used for their muscle relaxant and anticonvulsant properties. Benzodiazepines may be helpful in the short-term management of anxiety and sleep disturbances, but they must be used with caution because of the risk of dependence and abuse, even when used at therapeutic doses for short periods. Some commonly used benzodiazepines include diazepam, oxazepam, nitrazepam and temazepam.

Current scheduling status

A class entry for Benzodiazepine derivatives is currently listed in Schedule 4, except when separately specified in the Schedules. The majority of individually listed benzodiazepines are in Schedule 4.

Scheduling history

Benzodiazepines were listed in Schedule 4 as a class entry in the Poisons Standard ensuring new benzodiazepine derivatives, including those prepared by simple manipulation of drug molecules, would be captured by the existing Schedule entry, in accordance with the United Nations Convention on Psychotropic Substances 1971 (the Convention).

In May 1986 in response to a request from the Western Australian Health Department, the Committee agreed to include 10 separate benzodiazepine substances in Schedule 4 and amend the benzodiazepine class entry to exclude those that were separately specified.

In February 1987, the individual benzodiazepine substances were listed in Appendix K as drugs required to be labelled with warning statements.

In February 1996, the National Drugs and Poisons Schedule Committee (NDPSC) considered a report of an overdose resulting in death and the New South Wales State Coroner concerns regarding the appropriateness of the current benzodiazepines scheduling. The Committee considered the new information, and concluded that rescheduling of the drugs would not have prevented the overdose, noting that the States and Territories have procedures in place to deal with such matters and that the appropriate prescription and dispensing of Schedule 4 drugs to be the professional responsibility of medical practitioners and pharmacists. The Committee considered that benzodiazepines were appropriately scheduled in Schedule 4 and that strategies other than those available via the scheduling mechanism were more appropriate.

In November of 1997, the benzodiazepine substance flunitrazepam was rescheduled from Schedule 4 to Schedule 8 due to public health concerns. The NDPSC agreed that, while from a scientific standpoint flunitrazepam is no different from other substances in the benzodiazepine class, the health concerns related to the use and accessibility of flunitrazepam lead to its inclusion in Schedule 8.

In August of 1998, a class review of benzodiazepines based on the up-scheduling of flunitrazepam was conducted by the committee. The NDPSC recognised that benzodiazepines were useful therapeutic products and generally there are no suitable substitutes for their legitimate therapeutic uses. The Committee also noted that rescheduling would impose additional difficulties and costs for manufacturers, pharmacists, patients and the PBS system. A majority of the public submissions received advocated for the retention of benzodiazepines in Schedule 4, resulting in no change to the scheduling. The appropriateness of the scheduling was again reaffirmed in 1999.

Alprazolam was scheduled in November 1981, and was added to Appendix K in November 1987 as it was included in a list of substances of concern by the Australian Federal Police. In October 2007, the Department of Health in Tasmania introduced monthly reporting requirements of Alprazolam due to concerns of misuse. Rescheduling Alprazolam as a Schedule 8 substance was considered in June 2010. However, there was insufficient evidence to support a Schedule 8 restriction for alprazolam, and advised that the Schedule 4 entry remained appropriate.

In November 1971, temazepam is individually specified in Schedule 4, with appendix K entry added in February 1987. At the February and June 2004 meetings, the NDPSC considered a proposal to reschedule temazepam soft gel capsules to Schedule 8 due to illicit drug abuse market. Following the deferral from the February meeting, the sponsor of the product voluntarily withdrew the soft gel capsule products from the ARTG, with temazepam remaining in Schedule 4.

The following benzodiazepines were included in Schedule 4 by individual specification between 1965 and 1998 without an Appendix K entry: Bromazepam, Chlordiazepoxide, Clonazepam, Clorazepate, Clobazam, Diazepam, Flurazepam, Ketazolam, Loprazolam, Lorazepam, Lormetazepam, Medazepam, Midazolam, Nitrazepam, Oxazepam, Prazepam, Quazepam and Triazolam.

In 2013, the Advisory Committee on Medicines Scheduling (ACMS) considered a proposal to reschedule benzodiazepines from Schedule 4 to Schedule 8. The Committee recommended: (1) that alprazolam be rescheduled from Schedule 4 to Schedule 8; (2) that the scheduling of the remaining benzodiazepines remained appropriate; and (3) that benzodiazepines be included in Appendix D, paragraph 5.

Pre-meeting public submissions

No submissions were received.

Summary of ACMS advice to the delegate

The Committee advised that the:

  • following substances, not previously scheduled, be separately specified in Schedule 9: dicyclazepam, pyrazolam, clonazolam, deschloroetizolam, flubromazepam, nifoxipam and meclonazepam.
  • current scheduling of benzodiazepine derivative (Class entry) otherwise remains appropriate.
  • The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included: (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.
  • The reasons for the advice comprised the following:
    • Potential for abuse is high, with possible future compounds being designed to increase abuse potential.
    • Benefit may include potential for new drug classes that have not been developed for different therapeutic use.
    • Some substances captured by the term "Benzodiazepine derivatives" are marketed overseas as legitimate medicines. This term should remain in the same schedule as the majority of individually listed benzodiazepines, namely Schedule 4.
    • The term "Benzodiazepine derivatives" captures both substances with legitimate medical uses and substances primarily used as drugs of abuse. Although longer term use of benzodiazepines results in physical dependency the potential for abuse of the class overall would fit the criteria for a Schedule 4 substance.
    • New entries in Schedule 9 for dicyclazepam, pyrazolam, clonazolam, deschloroetizolam, flubromazepam, nifoxipam and meclonazepam as they currently have no known therapeutic use in Australia and are contained in no registered products, but are available overseas.
Delegate's considerations

The delegate considered the following in regards to this proposal:

  • Scheduling proposal;
  • ACCS advice;
  • Section 52E of the Therapeutic Goods Act 1989;
  • Scheduling factors18;
  • Other relevant information.
Delegate's interim decision

The delegate's interim decision is that:

  • dicyclazepam, pyrazolam, clonazolam, deschloroetizolam, flubromazepam, nifoxipam and meclonazepam, not previously scheduled, be separately specified in Schedule 9; and
  • the current scheduling of other benzodiazepines remains appropriate.

The proposed implementation date is 1 October 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; and f) any other matters that the Secretary considers necessary to protect public health.

The reasons for the decision comprised the following:

  • Potential for abuse is high, with possible future compounds being designed to increase abuse potential.
  • Benefit may include potential for new drug classes that have not been developed for different therapeutic use.
  • Some substances captured by the term "Benzodiazepine derivatives" are marketed overseas as legitimate medicines. This term should remain in the same schedule as the majority of individually listed benzodiazepines, namely Schedule 4.
  • The term "Benzodiazepine derivatives" captures both substances with legitimate medical uses and substances primarily used as drugs of abuse. Although longer term use of benzodiazepines results in physical dependency the potential for abuse of the class overall would fit the criteria for a Schedule 4 substance.
  • New entries in Schedule 9 for dicyclazepam, pyrazolam, clonazolam, deschloroetizolam, flubromazepam, nifoxipam and meclonazepam as they currently have no known therapeutic use in Australia and are contained in no registered products, but are available overseas.
Public submissions on the interim decision

No 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.


Footnotes

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

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