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Scheduling delegate's interim decisions and invitation for further comment: ACCS/ACMS, March 2016
Scheduling medicines and poisons
3.3 Benzodiazepine derivatives
Part A - Interim decisions on scheduling proposals referred to an advisory committee (March 2016)
3. Advisory Committee on Medicines Scheduling (ACMS#17)
3.3 Benzodiazepine derivatives
Referred 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.
Delegate-initiated application. The reasons for the request were:
- 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.
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.
Specific questions raised by the delegate
The delegate asked the committee; for benzodiazepines not specifically specified in Schedule 8 or Schedule 9 what would be the appropriate scheduling to achieve the ACMS suggested outcome?
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.
Relevant scheduling history
Benzodiazepines were added to the standard in Schedule 4 as a class entry, 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 nited 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 Committee 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 committee 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 Committee 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 committee 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 gelcap 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 Committee 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.
Public pre-meeting submissions
Summary of ACMS advice to the delegate at the March 2016 meeting
The ACMS recommended that the following substances, not previously scheduled, be separately specified in Schedule 9: dicyclazepam, pyrazolam, clonazolam, deschloroetizolam, flubromazepam, nifoxipam and meclonazepam. They also recommended that the 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:
- The potential for abuse is high, with possible future compounds being designed to increase abuse potential.
- Benefits 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 specific benzodiazepines capture substances with no known therapeutic use in Australia and are contained in no registered products, but which are available overseas.
The delegate considered the following in regards to this proposal:
- Scheduling proposal;
- ACMS advice;
- Section 52E of the Therapeutic Goods Act 1989;
- Scheduling factors18;
- Other relevant information.
Delegate's interim decision
The delegate has considered and agrees with the advice and reasons of the ACMS.
The proposed implementation date is 1 October 2016.
The delegate considered the relevant matters under section 52E (1) of the Therapeutic Goods Act 1989: (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.
Schedule 9 - New entries