Scheduling delegate's final decisions: ACMS, October 2014

Scheduling medicines and poisons

23 October 2014

Notice under subsections 42ZCZS and 42ZCZX of the Therapeutic Goods Regulations 1990 (the Regulations)

A delegate of the Secretary to the Department of Health hereby gives notice of the delegate's final decisions for amending the Poisons Standard (commonly referred to as the Standard for the Uniform Scheduling of Medicines and Poisons - SUSMP) under subsections 42ZCZS and 42ZCZX of the Therapeutic Goods Regulations 1990 (the Regulations). This notice also provides the reasons for each decision and the date of effect (implementation date) of the decision.

The delegate's final decisions and reasons relate to:

  • scheduling proposals initially referred to the July 2014 meeting of the Advisory Committee on Medicines Scheduling (ACMS#12 );
  • scheduling proposals considered as delegate-only matters, i.e. not referred to an expert advisory committee.

Scheduling proposals referred to the expert advisory committees

Pre-meeting public notice

A 'pre-meeting' public notice inviting submissions on the scheduling proposals referred to the expert advisory committees was published on 3 April 2014 at Consultation: Invitation for public comment - ACMS meeting, July 2014 and Consultation: Invitation for public comment - ACCS, ACMS and joint ACCS/ACMS meetings, July 2014, respectively.

Edited versions of these public submissions received in response to this invitation were published on 18 September 2014 at Public submissions on scheduling matters referred to the ACMS#12 (July 2014).

Interim decisions

The delegate's interim decisions on recommendations by the ACMS#12 were published on 18 September 2014 at Reasons for scheduling delegate's interim decision and invitation for further comment for the ACCS and the Joint ACCS-ACMS, June 2014. This public notice also invited further comment from the applicant and from those parties who made a valid submission in response to the original invitation for submissions.

Further submissions from parties other than those who made a valid submission in response to the original invitation or the applicant, or those received after the closing date, may not be considered by the delegate.

Edited versions of valid public submissions received in response to the interim decisions were published on 23 October 2014 and are available at Reasons for scheduling delegate's interim decisions & invitations for further comment.

Final decisions

In accordance with subsection 42ZCZR of the Regulations, if a delegate makes an interim decision on an application, the delegate may make a final decision either, confirming, varying or setting aside the interim decision, but only after considering any valid submissions received in response to the interim decisions.

Matters not referred to an advisory committee

A delegate may decide not to refer a scheduling proposal to an expert advisory committee for advice and instead may make a delegate-only decision. When deciding not to refer a matter to a committee, the delegate considers the scheduling guidelines as set out in the Scheduling Policy Framework for Medicines and Chemicals (SPF, 2010).

Publishing of the amendments to the Poisons Standard

The amendments to the Schedules, Appendices or other parts of the Poisons Standard are published electronically on ComLaw as amendments to the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP) The Poisons Standard (the SUSMP).

Contents

Glossary

Scheduling medicines and poisons

Abbreviation Name
AAN Australian Approved Name
AC Active constituent
ACCC Australian Competition and Consumer Commission
ACCM Advisory Committee on Complementary Medicines (formerly Complementary Medicine Evaluation Committee [CMEC])
ACNM Advisory Committee on Non-prescription Medicines (formerly Medicines Evaluation Committee [MEC])
ACPM Advisory Committee on Prescription Medicines (formerly Australian Drug Evaluation Committee [ADEC])
ACSOM Advisory Committee on the Safety of Medicines (formerly Adverse Drug Reactions Advisory Committee [ADRAC])
ADEC Australian Drug Evaluation Committee (now Advisory Committee on Prescription Medicines [ACPM])
ADI Acceptable daily intake
ADRAC Adverse Drug Reactions Advisory Committee (now Advisory Committee on the Safety of Medicines [ACSOM])
AHMAC Australian Health Ministers' Advisory Council
APVMA Australian Pesticides and Veterinary Medicines Authority
AQIS Australian Quarantine and Inspection Service
ARfD Acute reference dose
ASCC Australian Safety and Compensation Council
ASMI Australian Self-Medication Industry
ARTG Australian Register of Therapeutic Goods
CAS Chemical Abstract Service
CHC Complementary Healthcare Council of Australia
CMEC Complementary Medicine Evaluation Committee (now Advisory Committee on Complementary Medicines [ACCM])
CMI Consumer Medicine Information
COAG Councils of Australian Governments
CRC Child-resistant closure
CTFAA Cosmetic, Toiletry & Fragrance Association of Australia
CWP Codeine Working Party
DAP Drafting Advisory Panel
ECRP Existing Chemicals Review Program
EPA Environmental Protection Authority
ERMA Environmental Risk Management Authority (New Zealand)
FAISD First Aid Instructions and Safety Directions
FDA Food and Drug Administration (United States)
FOI Freedom of Information Act 1982
FSANZ Food Standards Australia New Zealand
GHS Globally Harmonised System for Classification and Labelling of Chemicals
GIT Gastro-intestinal tract
GP General practitioner
HCN Health Communication Network
IMAP Inventory Multi-tiered Assessment Prioritisation
INN International Non-proprietary Name
ISO International Standards Organization
LC50 The concentration of a substance that produces death in 50 per cent of a population of experimental organisms. Usually expressed as mg per litre (mg/L) as a concentration in air.
LD50 The concentration of a substance that produces death in 50 per cent of a population of experimental organisms. Usually expressed as milligrams per kilogram (mg/kg) of body weight.
LOAEL Lowest observed adverse effect level
LOEL Lowest observed effect level
MCC Medicines Classification Committee (New Zealand)
MEC Medicines Evaluation Committee (now Advisory Committee on Non-prescription Medicines [ACNM])
MOH Ministry of Health (New Zealand)
NCCTG National Coordinating Committee on Therapeutic Goods
NDPSC National Drugs and Poisons Schedule Committee
NHMRC National Health and Medical Research Council
NICNAS National Industrial Chemicals Notification & Assessment Scheme
NOAEL No observed adverse effect level
NOEL No observable effect level
NOHSC National Occupational Health & Safety Commission
OCM Office of Complementary Medicines
OCSEH Office of Chemical Safety and Environmental Health (now Office of Chemical Safety [OCS])
OCS Office of Chemical Safety (formerly Office of Chemical Safety and Environmental Health [OCSEH])
ODA Office of Devices Authorisation
OMA Office of Medicines Authorisation (formerly Office of Prescription and Non-prescription Medicines)
OOS Out of session
OTC Over-the-counter
PACIA Plastics and Chemicals Industries Association
PAR Prescription animal remedy
PBAC Pharmaceutical Benefits Advisory Committee
PEC Priority existing chemical
PGA Pharmaceutical Guild of Australia
PHARM Pharmaceutical Health and Rational Use of Medicines
PI Product Information
PIC Poisons Information Centre
PSA Pharmaceutical Society of Australia
QCPP Quality Care Pharmacy Program
QUM Quality Use of Medicines
RFI Restricted flow insert
SCCNFP Scientific Committee on Cosmetic and Non-Food Products
SCCP Scientific Committee on Consumer Products
STANZHA States and Territories and New Zealand Health Authorities
SUSDP Standard for the Uniform Scheduling of Drugs and Poisons
SUSMP Standard for the Uniform Scheduling of Medicines and Poisons
SVT First aid for the solvent prevails
TCM Traditional Chinese medicine
TGA Therapeutic Goods Administration
TGC Therapeutic Goods Committee
TGO Therapeutic Goods Order
TTHWP Trans-Tasman Harmonisation Working Party
TTMRA Trans-Tasman Mutual Recognition Agreement
WHO World Health Organization
WP Working party
WS Warning statement

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

Scheduling medicines and poisons

1. Scheduling proposals referred to the July 2014 meeting of the Advisory Committee on Medicines Scheduling (ACMS#12)

1.1 Amorolofine

Scheduling proposal

The medicines scheduling delegate considered a proposal to amend the Schedule 2 amorolfine entry to exempt from scheduling preparations for the treatment of onychomycoses (fungal infections of the nail).

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Amorolfine is a morpholine derivative with antifungal activity. It acts by interfering with the synthesis of sterols essential for the functioning of fungal cell membranes. Amorolfine is active in vitro against a wide variety of pathogenic and opportunistic fungi including dermatophytes, Blastomyces dermatitidis, Candida spp., Histoplasma capsulatum, and Sporothrix schenckii. It also has variable activity against Aspergillus spp. However, despite its in vitro activity, amorolfine is inactive when given systemically and this limits its use to topical application for superficial infections.

For the treatment of nail infections caused by dermatophytes, yeasts, and moulds a lacquer containing the equivalent of 5% amorolfine is painted onto the affected nail once or sometimes twice weekly until the nail has regenerated. Treatment generally needs to be continued for 6 to 12 months. For skin infections, including dermatophyte infections, a cream containing the equivalent of 0.25% amorolfine is applied once daily for at least 2 to 3 weeks (up to 6 weeks for foot infections) and continued for 3 to 5 days after clinical cure is achieved.

Scheduling status

Amorolfine is currently listed in Schedule 2 and Schedule 4 of the SUSMP.

Schedule 2

AMOROLFINE for topical use except in preparations for the treatment of tinea pedis.

Schedule 4

AMOROLFINE except:

  1. when included in Schedule 2; or
  2. in preparations for the treatment of tinea pedis.
Scheduling history

In February 1995, the National Drug and Poisons Scheduling Committee (NDPSC) considered the outcome of the 173rd Australian Drug Evaluation Committee (ADEC) meeting, which approved the registration of amorolfine. Based on this approval, the committee scheduled amorolfine in Schedule 4.

The NDPSC considered a proposal to place amorolfine in Schedule 2 for topical preparations containing 5% or less of the substance for the treatment of nail infections in February 1998. The committee felt that with inadequate safety data regarding the long term use, the ADEC consideration of the product for registration and the concern that consumers could not accurately diagnosis the condition without medical advice, the scheduling remained appropriate as Schedule 4.

The sponsor requested the committee to reconsider the proposal in May 1998. The sponsor provided further information addressing the NDPSC concerns and the committee noted that other aspects of the application were not give adequate consideration. The committee decided to review the application, pending information from the sponsor.

Amorolfine next appeared in the scheduling history records in August 1999. During this time, a Schedule 3 entry for the substance had been either considered or recommended, but no record of this could be located. Based on a recommendation from the Trans-Tasman Harmonisation Working Party (TTHWP), the Schedule 4 and 3 entries were to be amended and a new Schedule 2 entry was to be created for topical preparations containing 0.25% or less of amorolfine. This recommendation was in line with New Zealand’s entry for creams treating tinea pedis and the Schedule 3 equivalent for nail lacquers. The committee also agreed on an Appendix H entry for the substance.

During discussions at the November 1999 meeting, the committee noted that the amendments suggested in August 1999 followed the consideration of proposals from the product sponsor and the TTHWP, with the sponsor requesting the Schedule 3 entry and Appendix H listing and the TTHWP recommending the Schedule 2 entry. The NDPSC supported the proposals and the committee accepted the findings of the AHMAC committee in relation to the matters mentioned in subsection 52E (1) of the Act. The Schedule 4 and 3 entries were amended and the Schedule 2 entry outlined in August 1999 was accepted.

In October 2005, the NDPSC reviewed the scheduling of amorolfine, including the TTHWP recommendations. They noted that in NZ, amorolfine products containing 0.25% or less of the substance for the treatment of tinea pedis were general sale (exempt from scheduling). Harmonisation was supported on the basis of history of safe use in NZ and the committee foreshadowed amending the Schedule 2 entry to exempt preparations for the treatment of tinea pedis.

In February 2006, the committee confirmed the foreshadowed decisions outlined in October 2005 on the grounds of harmonisation.

Amorolfine was considered as part of a group item relating to substances that are applied to nails and clarifying their scheduling entries in June 2006. The committee reviewed the history of the scheduling decisions, and discussed substance details and possible amendments to the amorolfine entries, in an effort to be consistent with other substance entries relating to the fungal treatment of nails. The members agreed that an amendment for consistency was not appropriate in this case.

In June 2010 the committee discussed an application from the product sponsor requesting that all topical use preparations of amorolfine, regardless of strength, be rescheduled from Schedule 3 to Schedule 2. The applicant stated that there was low potential for harm from inappropriate use and low abuse potential, low or well characterised incidence of adverse effects, the condition onychomycosis is easily recognisable by the consumer and amenable to short-term treatment and that there are positive benefits for consumers. The committee agreed to remove the Schedule 3 entry and place all topical preparations in Schedule 2 on the grounds the risk posed by the substance was similar to other schedule 2 anti-fungals and that any risk would be addressed by labelling. The exemption for preparations treating tinea pedis remained.

In June 2011, the medicines delegate agreed with an ACMS member's comments that now there was no longer a Schedule 3 entry for the substance, the Appendix H entry was no longer needed and the delegate decided that it would be removed.

Pre-meeting public submissions

Two submissions were received; both did not support the proposal. The first submission was of the belief that access to health professionals is required for correct use of treatments and that underlying or related health conditions associated with onychomycosis are examined and referred to medical practitioners where appropriate. Conveying similar reasons, the second submission felt that consumers using amorolfine should have the opportunity for immediate access to pharmacist advice to support appropriate self-medication practices, tailor therapy and promote optimal outcomes from therapy.

ACMS advice to the delegate

The ACMS recommended that the current scheduling of amorolfine remains appropriate.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included: b) the purpose for which a substance is to be used and the extent of use of a substance.

The reasons for the recommendation comprised the following:

  • The diagnosis of onychomycoses can be difficult and treatment requires long term use of amorolfine. Consequently, the patient will benefit from having access to professional advice in both initiating and maintaining treatment.
Delegate's interim decision

The interim decision is that the current scheduling of amorolfine remains appropriate.

Reasons for the decision are:

  • Concerns about the ability to self-diagnosis onychomycosis (or) fungal nail infections, particularly in people with diabetes. The main reason for this is that visible symptoms of fungal infections (discolouration of the nail) could mask those of underlying diabetic issues, such as impaired blood circulation. The minimum treatment period of onychomycoses is six months.
  • This interim decision is supported by the applicant's statement that diagnosis of onychomycoses is difficult and that public awareness of onychomycoses is limited.
  • No other comparable country has amorolfine available as a general sale product.
  • No other antifungal is exempt from scheduling except for the treatment of tinea pedis.
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 factors1;
  • Other relevant information.
Public submissions on the interim decision

One submission was received that did not support delegate's interim decision on the basis that definitive diagnosis any fungal condition is difficult, people with diabetes are usually under care of a medical practitioner/specialist and the Consumer Medicine Information provides relevant advice.

Edited versions of these submissions are available at Public submissions on scheduling matters.

Delegate's final decision

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

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1.2 Calcium hydroxylapatite

Scheduling proposal

The medicines scheduling delegate considered a proposal to include calcium hydroxylapatite in preparations for injection or implantation when used for tissue augmentation or for cosmetic use in Schedule 4.

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Hydroxylapatite (also known as hydroxyapatite) is a natural mineral with a composition similar to that of the mineral in bone. For therapeutic purposes, hydroxylapatite is prepared from bovine bone and contains, in addition to calcium and phosphate, trace elements, fluoride and other ions, proteins and glycosaminoglycans. It is given orally to patients requiring both calcium and phosphorus supplementation and hydroxylapatite with tricalcium phosphate has been used in bone grafts.

Hydroxylapatite derived from marine coral has been used in the construction of orbital implants for use after surgical removal of the eye. A form of hydroxyapatite referred to as calcium hydroxyapatite is used for correction of facial lipoatrophy in patients with HIV infection and as a cosmetic filler for moderate to severe facial wrinkles and folds.2

Scheduling status

Calcium hydroxylapatite is not specifically scheduled.

Scheduling history

Calcium hydroxylapatite has not been previously considered for scheduling therefore scheduling history is not available.

Pre-meeting public submissions

One public submission was received, asking the committee and the delegate to consider that the substance is used in dental bone grafting medical devices, entry could potentially impact on these products, suggested exempting the substance for dental use.

ACMS advice to the delegate

The ACMS recommended that calcium hydroxylapatite in preparations for injection or implantation when used for tissue augmentation or for cosmetic use be included in Schedule 4 with an implementation date of 1 February 2015.

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; 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 recommendation comprised the following:

  • There needs to be appropriate monitoring and reporting of adverse effects.
  • There is the potential for inappropriate off-label administration.
  • An injectable implant needs to be administered by a health practitioner who has knowledge and training in injection/implantation techniques, uses appropriate infection control procedures and undertakes appropriate follow-up. There is potential for serious adverse effects if the administration of the product is not undertaken by an appropriately trained and qualified practitioner.

There is potential for inappropriate advertising direct to consumers. Concurrent administration of local anaesthetic may be required and this should be administered by an appropriately qualified health practitioner.

Delegate's interim decision

The interim decision is that calcium hydroxylapatite in preparations for injection or implantation when used for tissue augmentation or for cosmetic use be included in Schedule 4 with an implementation date of 1 February 2015.

The reasons for the interim decision are:

  • An injectable implant needs to be administered by a health practitioner who has knowledge and training in injection/implantation techniques, uses appropriate infection control procedures and undertakes appropriate follow-up. There is potential for serious adverse effects if the administration of the product is not undertaken by an appropriately trained and qualified practitioner.
  • Concurrent administration of local anaesthetic may be required and this should be administered by an appropriately qualified health practitioner.
  • There is potential for inappropriate advertising direct to consumers.
  • There needs to be appropriate monitoring and reporting of adverse effects.
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 factors3;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

Schedule entry
Schedule 4 - New entry

CALCIUM HYDROXYLAPATITE in preparations for injection or implantation:

  1. for tissue augmentation; or
  2. for cosmetic use.

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1.3 Macitentan

Scheduling proposal

The medicines scheduling delegate considered a proposal to include macitentan in Appendix D, Item 2 and Appendix L.

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Macitentan belongs to the same class of pharmaceuticals as bosentan and ambrisentan and the former sitaxentan (withdrawn globally due to liver toxicity) which are orally active endothelin receptor antagonists (ERAs). Macitentan, like bosentan, is a dual endothelin A and B receptor antagonist, which is different to ambrisentan which is specific for endothelin type A receptors.

Macitentan is proposed for the long-term treatment of pulmonary arterial hypertension (PAH) in patients of WHO Functional Class II to IV, as monotherapy or in combination with approved PAH treatments (phosphodiesterase-5 inhibitors or prostanoids) to delay disease progression.

Scheduling status

Macitentan is not currently scheduled in Australia. Macitentan has just been considered by the New Zealand Medsafe Committee as a prescription medication. It is also considered a prescription drug in the United States of America (USA), Canada and the European Union. Macitentan is considered by the USA as a Pregnancy Category X drug. In Canada and in the EU the substance is contraindicated during pregnancy and for nursing women.

Scheduling history

Macitentan has not been previously considered for scheduling therefore scheduling history is not available.

Pre-meeting public submissions

No submissions were received for this scheduling proposal.

ACMS advice to the delegate

The ACMS recommended that Macitentan be included in Appendix D, Item 6 as well as Appendix L with warning statements 7, 62 and 76 with an implementation date of 1 February 2015.

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 and c) the toxicity of the substance.

The reasons for the recommendation comprised the following:

  • Teratogenicity which is consistent with other substances in this class

The need for product information containing contraindications during pregnancy.

Delegate's interim decision

The interim decision is to include macitentan in Appendix D, Item 6 as well as Appendix L with warning statements 7, 62 and 76 with an implementation date of 1 February 2015.

The reasons for the interim decision are:

  • Its teratogenicity which is consistent with other substances in this class which have this scheduling.
  • The need for product information containing contraindications during pregnancy.
  • That it is considered by the USA as a Pregnancy Category X drug.

That in Canada and in the EU the substance is contraindicated during pregnancy and for nursing women.

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 factors4;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

Schedule entry
Appendix D, Item 6 - New entry

MACITENTAN for human use

Appendix L, Part 2 - New entry
Column 1
Substance
Column 2
Warning statement
Macitentan 7, 62 and 76

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1.4 Polycaprolactone

Scheduling proposal

The medicines scheduling delegate considered a proposal to include polycaprolactone in preparations for injection or implantation when used for tissue augmentation or for cosmetic use in Schedule 4.

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

A substance summary for polycaprolactone was not provided for this proposal.

Scheduling status

Polycaprolactone is not specifically scheduled.

Scheduling history

Polycaprolactone has not been previously considered for scheduling therefore scheduling history is not available.

Pre-meeting public submissions

No submissions were received for this scheduling proposal.

ACMS advice to the delegate

The ACMS recommended that polycaprolactone in preparations for injection or implantation when used for tissue augmentation or for cosmetic use be included in Schedule 4 with an implementation date of 1 February 2015.

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; 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 recommendation comprised the following:

  • There needs to be appropriate monitoring and reporting of adverse effects.
  • There is the potential for inappropriate off-label administration.
  • An injectable implant needs to be administered by a health practitioner who has knowledge and training in injection/implantation techniques, uses appropriate infection control procedures and undertakes appropriate follow-up. There is potential for serious adverse effects if the administration of the product is not undertaken by an appropriately trained and qualified practitioner.
  • There is potential for inappropriate advertising direct to consumers. Concurrent administration of local anaesthetic may be required and this should be administered by an appropriately qualified health practitioner.
Delegate's interim decision

The interim decision is that polycaprolactone in preparations for injection or implantation when used for tissue augmentation or for cosmetic use is included in Schedule 4 with an implementation date of 1 February 2015.

Reasons for the interim decision are:

  • An injectable implant needs to be administered by a health practitioner who has knowledge and training in injection/implantation techniques, uses appropriate infection control procedures and undertakes appropriate follow-up. There is potential for serious adverse effects if the administration of the product is not undertaken by an appropriately trained and qualified practitioner.
  • Concurrent administration of local anaesthetic may be required and this should be administered by an appropriately qualified health practitioner.
  • There needs to be appropriate monitoring and reporting of adverse effects.
  • There is potential for inappropriate advertising direct to consumers.
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 factors5;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

Schedule entry
Schedule 4 - New entry

POLYCAPROLACTONE in preparations for injection or implantation:

  1. for tissue augmentation; or
  2. for cosmetic use.

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1.5 Riociguat

Scheduling proposal

The medicines scheduling delegate considered a proposal to include riociguat in Appendix D, Item 2 and Appendix L.

Substance summary

Riociguat is a stimulator of soluble guanylate cyclase, an enzyme in the cardiopulmonary system, and increases production of the second messenger cyclic guanosine monophosphate (cGMP).

Adempas (riociguat) is proposed to be used in adult patients with chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension.

Scheduling status

Riociguat is not currently scheduled in Australia or New Zealand. It is, however, a prescription drug in the United States of America (USA), Canada and the European Union. Riociguat is considered by the USA as a Pregnancy Category X drug. In Canada and in the EU the substance is contraindicated during pregnancy and for nursing women.

Scheduling history

Riociguat has not been previously considered for scheduling therefore scheduling history is not available.

Pre-meeting public submissions

No submissions were received for this scheduling proposal.

ACMS advice to the delegate

The ACMS recommended that riociguat be included in Appendix D, Item 4 as well as Appendix L with warning statements 7, 62 and 76 with an implementation date of 1 February 2015.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the Committee included: c) the toxicity of the substance.

The reason for the recommendation comprised the following:

  • Teratogenic nature of the substance.
Delegate's interim decision

The interim decision is that riociguat is included in Appendix D, Item 4, as well as Appendix L with warning statements 7, 62 and 76 with an implementation date of 1 February 2015.

The reasons for the interim decision are:

  • The teratogenic nature of the substance.
  • FDA have stipulated a 1 month washout period
  • It is considered by the USA as a Pregnancy Category X drug.
  • That in Canada and in the EU the substance is contraindicated during pregnancy and for nursing women.
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 factors6;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

Schedule entry
Appendix D, Item 4 - New entry

RIOCIGUAT for human use

Appendix L, Part 2 - New entry
Column 1
Substance
Column 2
Warning statement
Riociguat 7, 62 and 76

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1.6 Suvorexant

Scheduling proposal

The medicines scheduling delegate considered a proposal to include suvorexant in Appendix K.

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Suvorexant is a dual orexin receptor antagonist and is indicated for the treatment of insomnia, characterised by difficulties with sleep onset and/or sleep maintenance.

Scheduling status

Suvorexant is not currently scheduled in Australia or New Zealand. It is currently under review by the Food and Drug Administration (FDA) in the United States of America (USA). The FDA is yet to approve suvorexant due to concerns regarding the safety and efficacy of the substance.

Scheduling history

Suvorexant has not been previously considered for scheduling therefore scheduling history is not available.

Pre-meeting public submissions

No submissions were received for this scheduling proposal.

ACMS advice to the delegate

The ACMS recommended that suvorexant be included in Appendix K with an implementation date of 1 February 2015.

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 and c) the toxicity of the substance.

The reasons for the recommendation comprised the following:

  • Pronounced sedation effect
  • Entry would be consistent with other sedative drugs in Appendix K
  • Long duration of action of the substance may impact on peoples’ ability to drive and operate machinery
  • Narrow therapeutic margin.
Delegate's interim decision

The interim decision is that suvorexant be included in Appendix K.

Reasons for the interim decision are:

  • Pronounced sedation effect
  • Entry would be consistent with other sedative drugs in Appendix K
  • Long duration of action of the substance may impact on peoples’ ability to drive and operate machinery
  • Narrow therapeutic margin of the substance.
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 factors7;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

Schedule entry
Appendix K - New entry

SUVOREXANT

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1.7 Tofactinib

Scheduling proposal

The medicines scheduling delegate considered a proposal to include tofacitinib in Appendix D and Appendix L.

The delegate referred the proposal to the Advisory Committee on Medicines Scheduling (ACMS) for advice.

Substance summary

Tofacitinib is a JAK1, 2 and 3 kinase inhibitor with some limited inhibitory activity against tyrosine kinase 2 (TyK2).

Scheduling status

Tofacitinib is not currently scheduled in Australia or New Zealand.

Scheduling history

Tofacitinib has not been previously considered for scheduling therefore scheduling history is not available.

Pre-meeting public submissions

No submissions were received for this scheduling proposal.

ACMS advice to the delegate

The ACMS recommended that tofacitinib does not require inclusion in Appendix D or Appendix L.

Delegate's interim decision

The interim decision is that tofacitinib does not require inclusion in Appendix D or Appendix L.

The reasons for the interim decision are:

  • Pregnancy is not contraindicated and as tofacitinib is considered pregnancy category D, it would not require an Appendix L listing.
  • As Appendix L is not required there is no need for a specialist prescription and hence does not require Appendix D listing.
  • USA has classified tofacitinib as Pregnancy Category C under their own classification system.
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 factors8;
  • Other relevant information.
Public submissions on the interim decision

No public submissions were received.

Delegate's final decision

The delegate has confirmed that the reasons for the final decision are in keeping with those for the interim decision.

Footnotes

Part B - Final decisions on matters not referred to an expert advisory committee

Scheduling medicines and poisons

2. New chemical entities - medicines for human therapeutic use

2.1 Bemdamustine

Scheduling proposal

The delegate considered the scheduling of bendamustine, a new chemical entity (a human therapeutic medicine).

Scheduling status

Bendamustine is the Internationally Nonproprietary Name (INN) and it is not specifically scheduled in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP). A related compound, mustine, is listed in the SUSMP No. 3 as follows:

Schedul 4

MUSTINE (nitrogen mustard)

Delegate's consideration

The delegate considered the following in regards to this application for scheduling.

  • Subsection 52E(1) of the Therapeutic Goods Act 1989
  • The Scheduling Policy Framework scheduling factors
  • The TGA evaluation report
  • The advice of the Advisory Committee on Prescription Medicines
  • The new drug application.
Delegate's final decision

The delegate has made a final decision to amend the SUSMP to include bendamustine in Schedule 4, with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of bendamustine; (b) the purpose and the extent of use of bendamustine; (c) the toxicity of bendamustine; d) the dosage, formulation, labelling, packaging and presentation of bendamustine; (e) the potential for abuse of bendamustine.

The delegate decided that the reasons for the final decision comprise the following:

  • This is a new chemical entity with limited clinical experience in Australia. The TGA has found a positive benefit-risk balance for bendamustine for specific uses.
  • Recommended use is limited to specified haemato-oncology indications.
  • Toxicity has been factored into the TGA appraisal of benefit - risk balance and is consistent with S4 scheduling.
  • These factors have been considered in the TGA appraisal of benefit - risk balance and are consistent with S4 scheduling.

The potential for abuse of bendamustine is unlikely.

Schedule entry
Schedule 4 - New entry

BENDAMUSTINE.

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2.2 Bosutinib

Scheduling proposal

The delegate considered the scheduling of bosutinib, a new chemical entity (a human therapeutic medicine).

Scheduling status

Bosutinib monohydrate is not specifically scheduled and is not captured by any entry in the Standard for the Uniform Scheduling of Medicines and Poisons.

Delegate's consideration

The delegate considered the following in regards to this application for scheduling.

  • Subsection 52E(1) of the Therapeutic Goods Act 1989
  • The Scheduling Policy Framework scheduling factors
  • The TGA evaluation report
  • The advice of the Advisory Committee on Prescription Medicines
  • The new drug application.
Delegate's final decision

The delegate has made a final decision to amend the SUSMP to include bosutinib in Schedule 4, with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of bosutinib; (b) the purpose and the extent of use of bosutinib; (c) the toxicity of bosutinib; d) the dosage, formulation, labelling, packaging and presentation of bosutinib; and (e) the potential for abuse of bosutinib.

The delegate decided that the reasons for the final decision comprise the following:

  • This is a new chemical entity with limited clinical experience in Australia. The TGA has found a positive benefit-risk balance for bosutinib for specific uses.
  • Recommended use is limited to specified haemato-oncology indications.
  • Toxicity has been factored into the TGA appraisal of benefit - risk balance and is consistent with S4 scheduling.
  • These factors have been considered in the TGA appraisal of benefit - risk balance and are consistent with S4 scheduling.
  • The potential for abuse of bosutinib is unlikely.
Schedule entry
Schedule 4 - New entry

BOSUTINIB.

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2.3 Brentuximab

Scheduling proposal

The delegate considered the scheduling of brentuximab vedotin, a new chemical entity (a human therapeutic medicine).

Scheduling status

Brentuximab vedotin is not specifically scheduled and is not captured by any entry in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).

Delegate's consideration

The delegate considered the following in regards to this application for scheduling.

  • Subsection 52E(1) of the Therapeutic Goods Act 1989
  • The Scheduling Policy Framework scheduling factors
  • The TGA evaluation report
  • The advice of the Advisory Committee on Prescription Medicines
  • The new drug application.
Delegate's final decision

The delegate has made a final decision to amend the SUSMP to include brentuximab vedotin in Schedule 4, with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of brentuximab vedotin; (b) the purpose and the extent of use of brentuximab vedotin; (c) the toxicity of brentuximab vedotin; d) the dosage, formulation, labelling, packaging and presentation of brentuximab vedotin; (e) the potential for abuse of brentuximab vedotin.

The delegate decided that the reasons for the final decision comprise the following:

  • This is a new chemical entity with limited clinical experience in Australia. The TGA has found a positive benefit-risk balance for brentuximab vedotin for specific uses.
  • Recommended use is limited to specified haemato-oncology indications.
  • Toxicity has been factored into the TGA appraisal of benefit - risk balance and is consistent with S4 scheduling.
  • These factors have been considered in the TGA appraisal of benefit - risk balance and are consistent with S4 scheduling.

The potential for abuse of brentuximab vedotin is unlikely.

Schedule entry
Schedule 4 - New entry

BRENTUXIMAB VEDOTIN.

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2.4 Carglumic acid

Scheduling proposal

The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of carglumic acid, a new chemical entity for a human therapeutic medicine.

Scheduling status

Carglumic acid is not specifically scheduled and is not captured by any entry in the Standard for the Uniform Scheduling of Medicines and Poisons.

Delegate's consideration

The delegate considered the following in regards to this application for scheduling.

  • Subsection 52E(1) of the Therapeutic Goods Act 1989
  • The Scheduling Policy Framework scheduling factors
  • The TGA evaluation report
  • The advice of the Advisory Committee on Prescription Medicines
  • The new drug application.
Delegate's final decision

The delegate has made a final decision to amend the SUSMP to include carglumic acid in Schedule 4 with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of a substance; (b) the purpose and the extent of use of a substance; and d) the dosage, formulation, labelling, packaging and presentation of a substance.

The delegate decided that the reasons for the final decision comprise the following:

  • It is a new chemical entity with no [clinical/marketing] experience in Australia.
  • The proposed therapeutic use relates to conditions requiring specialist care including acute care settings.
  • Labelling needs to comply with requirements of a prescription-only medicine.
Schedule entry
Schedule 4 - New entry

CARGLUMIC ACID (N-carbomoyl-L-glutamic acid).

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2.5 Elosulfase alfa

Scheduling proposal

The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of elosulfase alfa, a new chemical entity for a human therapeutic medicine.

Scheduling status

Elosulfase alfa is not specifically scheduled and is not captured by any entry in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).

Delegate's consideration

The delegate considered the following in regards to this application for scheduling.

  • Subsection 52E(1) of the Therapeutic Goods Act 1989
  • The Scheduling Policy Framework scheduling factors
  • The TGA evaluation report
  • The advice of the Advisory Committee on Prescription Medicines
  • The new drug application.
Delegate's final decision

The delegate has made a final decision to amend the SUSMP to include elosulfase alfa in Schedule 4, with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of; (b) the purpose and the extent of use of; (c) the toxicity of; d) the dosage, formulation, labelling, packaging and presentation of a substance; and (e) the potential for abuse.

The delegate decided that the reasons for the final decision comprise the following:

  • It is a new chemical entity with no clinical or marketing experience in Australia.
  • It has no previous experience of use in Australia but has recently been approved for use overseas.
  • Elosulfase alfa is indicated for the treatment of mucopolysaccharidosis type IVA (MPS IVA; Morquio A).
  • It is proposed for hospital use and home based use.
  • The risks and benefits of the medicine have been considered and are outlined in the Product Information.
  • Treatment should be supervised by a physician or healthcare provider experienced in the management of patients with MPS IVA or other inherited metabolic disorders.
  • The use of the medicine requires medical intervention, adjunctive therapy, evaluation and monitoring by a medical practitioner.
  • Labelling needs to comply with the requirements for a prescription only medicine.
  • It does not appear to produce dependency and the abuse potential appears to be low.
Schedule entry
Schedule 4 - New entry

ELOSULFASE ALFA.

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2.6 Macitentan

Scheduling proposal

The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of macitentan, a new chemical entity for a human therapeutic medicine.

Macitentan is a dual endothelin A and B receptor antagonist.

Macitentan, as monotherapy or in combination with approved PAH treatments (phosphodiesterase-5 inhibitors or inhaled prostanoids), is indicated for the treatment of:

  • idiopathic pulmonary arterial hypertension
  • heritable pulmonary arterial hypertension
  • pulmonary arterial hypertension associated with connective tissue disease
  • pulmonary arterial hypertension associated with congenital heart disease with repaired shunts in patients with WHO Functional class II, III or IV symptoms.

The delegate decided to make a delegate-only decision to include this to Schedule 4. The Advisory Committee on Medicines Scheduling (ACMS) was consulted due to the pregnancy Category X status of macitentan. The delegate has considered the committee's recommendation and macitentan is to be included in Appendix D and Appendix L (see Part A 1. Scheduling proposals referred to the July 2014 meeting of the Advisory Committee on Medicines Scheduling (ACMS# 12) of this document).

Scheduling status

Macitentan is not specifically scheduled and is not captured by any entry in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).

Macitentan is not classified in New Zealand.

Delegate's consideration

The delegate considered the following in regards to this application for scheduling:

  • The new drug application.
  • The TGA evaluation report.
  • The advice of the Advisory Committee on Prescription Medicines.
  • Subsection 52E(1) of the Therapeutic Goods Act 1989.
  • The Scheduling Policy Framework scheduling factors.
Delegates' final decision

The delegate has made a final decision to amend the SUSMP to include macitentan in Schedule 4, with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of; (b) the purpose and the extent of use of; (c) the toxicity of; d) the dosage, formulation, labelling, packaging and presentation of; and (e) the potential for abuse of macitentan.

The delegate decided that the reasons for the final decision comprise the following:

  • Macitentan is a new chemical entity with no clinical experience in Australia.
  • Macitentan has risks and benefits which are outlined in the Product Information.
  • It is indicated for the treatment of pulmonary arterial hypertension in certain subgroups as either monotherapy or in combination with other treatments and in patients with specific WHO functional classes.
  • Experience of its use is limited.
  • The drug has specific toxicities related to embryo-fetal risk and therefore is a category X drug and contraindicated in pregnancy or in women who may become pregnant.
  • Treatment with macitentan should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension. The use of the medicine requires medical intervention and monitoring by a medical practitioner.
  • Labelling needs to comply with the requirements for a prescription only medicine.
  • It does not appear to produce dependency and the abuse potential appears to be low.

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2.7 Riociguat

Scheduling proposal

The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of riociguat, a new chemical entity for a human therapeutic medicine.

Riociguat is a stimulator of soluble guanylate cyclase, an enzyme in the cardiopulmonary system, and increases production of the second messenger cyclic guanosine monophosphate (cGMP).

Adempas (riociguat) has the following indications:

Pulmonary arterial hypertension

Adempas, as monotherapy or in combination with approved PAH treatments (endothelin receptor antagonists or inhaled or subcutaneous prostanoids), is indicated for the treatment of:

  • idiopathic pulmonary arterial hypertension
  • heritable pulmonary arterial hypertension
  • pulmonary arterial hypertension associated with connective tissue diseases or
  • pulmonary arterial hypertension associated with congenital heart disease in adult patients with WHO functional Class II, lll or IV symptoms
Chronic thromboembolic pulmonary hypertension

Adempas is indicated for the treatment of:

  • persistent or recurrent chronic thromboembolic pulmonary hypertension (CTEPH) after surgical treatment or
  • inoperable CTEPH in adult patients with WHO functional Class II, III or IV symptoms.

The delegate decided to make a delegate-only decision to include this to Schedule 4. The Advisory Committee on Medicines Scheduling (ACMS) was consulted on the requirement for a sedation warning. The delegate has considered the committee's recommendation and riociguat is to be included in Appendix D and Appendix L (see Part A 1. Scheduling proposals referred to the July 2014 meeting of the Advisory Committee on Medicines Scheduling (ACMS# 12) of this document).

Scheduling status

Riociguat is not specifically scheduled and is not captured by any entry in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).

Riociguat is not classified in New Zealand.

Delegate's consideration

The delegate considered the following in regards to this application for scheduling.

  • The new drug application.
  • The TGA evaluation report.
  • The advice of the Advisory Committee on Prescription Medicines.
  • Subsection 52E(1) of the Therapeutic Goods Act 1989.
  • The Scheduling Policy Framework scheduling factors.
Delegate's final decision

The delegate has made a final decision to amend the SUSMP to include riociguat in Schedule 4, with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of; (b) the purpose and the extent of use of; (c) the toxicity of; d) the dosage, formulation, labelling, packaging and presentation of; and (e) the potential for abuse of riociguat.

The delegate decided that the reasons for the final decision comprise the following:

  • Riociguat is a new chemical entity with no clinical experience in Australia.
  • The risks and benefits are outlined in the Product Information, Delegate's Request for ACPM advice and the TGA evaluation reports.
  • It is proposed to be used in adult patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in certain subgroups as either monotherapy or in combination with other treatments and in patients with specific WHO functional classes.
  • Experience of its use is limited.
  • The use of riociguat requires medical intervention, adjunctive therapy and evaluation.
  • The drug has specific toxicities related to use in pregnancy and is proposed as a category X drug and contraindicated in pregnancy. It also has safety concerns with hypotension and bleeding and concomitant use with nitrates, nitric oxide donors and PDE-5 inhibitors.
  • Treatment with riociguat should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension.
  • The use of riociguat requires monitoring by a medical practitioner to minimize the risk of using it.
  • Medicine is packed as 0.5, 1.0, 1.5, 2.0 and 2.5 mg film-coated tablets in blister packs.
  • It does not appear to produce dependency and the abuse potential appears to be low.
Schedule entry
Schedule 4 - New entry

RIOCIGUAT.

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2.8 Simoctocog alfa

Scheduling proposal

The delegate considered the scheduling of simoctocog alfa, a new chemical entity (a human therapeutic medicine).

Scheduling status

Simoctocog alfa is not specifically scheduled in the Standard for the Uniform Scheduling of Medicines and Poisons.

Delegate’s consideration

The delegate considered the following in regards to this application for scheduling.

  • Subsection 52E(1) of the Therapeutic Goods Act 1989
  • The Scheduling Policy Framework scheduling factors
  • The TGA evaluation report
  • The advice of the Advisory Committee on Prescription Medicines
  • The new drug application.
Delegate's final decision

The delegate has made a final decision that simoctocog alfa falls under Appendix A - General Exemptions under Human Blood Products as it is an equivalent recombinant alternative to a plasma-derived clotting factor.

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2.9 Suvorexant

Scheduling proposal

The delegate considered an application from the Therapeutic Goods Administration (TGA) for the scheduling of suvorexant, a new chemical entity for a human therapeutic medicine.

Suvorexant is a dual orexin receptor antagonist.

Suvorexant was proposed to be indicated for the treatment of insomnia, characterised by difficulties with sleep onset and/or sleep maintenance.

The delegate decided to make a delegate-only decision to include this to Schedule 4. The Advisory Committee on Medicines Scheduling (ACMS) was consulted on the requirement for a sedation warning. The delegate has considered the committee's recommendation and suvorexant is to be included in Appendix K (see Part A 1. Scheduling proposals referred to the July 2014 meeting of the Advisory Committee on Medicines Scheduling (ACMS# 12) of this document).

Scheduling status

Suvorexant is not specifically scheduled and is not captured by any entry in the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP).

Suvorexant is not classified in New Zealand.

Delegate's consideration

The delegate considered the following in regards to this application for scheduling.

  • The new drug application.
  • Subsection 52E(1) of the Therapeutic Goods Act 1989.
  • The Scheduling Policy Framework scheduling factors.
Delegate's final decision

The delegate has made a final decision to amend the SUSMP to include suvorexant in Schedule 4, with an implementation date of 1 February 2015.

The delegate decided that the relevant matters under subsection 52E(1) of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of suvorexant.

The delegate decided that the reasons for the final decision comprise the following:

  • Suvorexant is a new chemical entity with no clinical or marketing experience in Australia.
  • The substance is intended to cause drowsiness and its effects are additive with alcohol.
  • The delegate made an initial decision to reject registration of suvorexant.
Schedule entry
Schedule 4 - New entry

SUVOREXANT.