Final scheduling decisions and reasons: NCEs and Appendix H

Final decisions and reasons for New Chemical Entities (NCEs) and Schedule 3 substances to be added to Appendix H of the Poisons Standard

12 December 2018

Publication of decisions pursuant to regulation 42ZCZX of the Therapeutic Goods Regulations 1990

In accordance with regulation 42ZCZX, this notice gives effect to the Secretary’s obligation to publish the final decisions, the reasons for those decisions and the date of effect of decisions made pursuant to regulations 42ZCZU or 42ZCZW of the Therapeutic Goods Regulations 1990.

The final decisions to which this notice relates include decisions made with respect to new therapeutic Prescription Only medicines known as New Chemical Entities (NCEs) which were not referred to an expert advisory committee. This notice also includes delegate approved changes to Appendix H.

Contents

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

  1. Delegate-only decisions on Schedule 3 substances to be added to Appendix H of the Poisons Standard 3
  2. New Chemical Entities - medicines for human therapeutic use

1.1. Appendix H

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

1. Delegate-only decisions on Schedule 3 substances to be added to Appendix H of the Poisons Standard

1.1. Appendix H

Delegate's final decision
Final decision:

The delegate's final decision is to amend Appendix H of the Poisons Standard as follows:

Appendix H - New entries:

ADRENALINE

CICLOPIROX

CLOBETASONE

FAMCICLOVIR

FLUORIDES

GLUCAGON

ISOCONAZOLE

KETOPROFEN

LEVONORGESTREL

NALOXONE

OXICONAZOLE

PARACETAMOL

PODOPHYLLOTOXIN

PODOPHYLLUM EMODI (podophyllin)

PODOPHYLLUM PELTATUM (podophyllin)

SALICYLIC ACID

TIOCONAZOLE

TRIAMCINOLONE

Index - Amend Entries

ADRENALINE

Schedule 4

Schedule 3

Appendix H

CICLOPIROX

Schedule 4

Schedule 3

Schedule 2

Appendix H

CLOBETASONE

Schedule 4

Schedule 3

Appendix F, Part 3

Appendix H

FAMCICLOVIR

Schedule 4

Schedule 3

Appendix H

FLUORIDES

cross reference: SILICOFLUORIDES

Schedule 6

Schedule 5

Schedule 4

Schedule 3

Schedule 2

Appendix E, Part 2

Appendix F, Part 3

Appendix H

GLUCAGON

Schedule 3

Appendix G

Appendix H

ISOCONAZOLE

Schedule 6

Schedule 4

Schedule 3

Schedule 2

Appendix H

KETOPROFEN

Schedule 4

Schedule 3

Appendix H

LEVONORGESTREL

Schedule 4

Schedule 3

Appendix H

NALOXONE

Schedule 4

Schedule 3

Appendix H

OXICONAZOLE

Schedule 4

Schedule 3

Schedule 2

Appendix H

PARACETAMOL

cross reference: ASPIRIN, IBUPROFEN, METOCLOPRAMIDE, SALICYLAMIDE, CAFFEINE

Schedule 4

Schedule 3

Schedule 2

Appendix F, Part 3

Appendix H

PODOPHYLLOTOXIN

cross reference: PODOPHYLLIN

Schedule 4

Schedule 3

Schedule 2

Appendix F, Part 3

Appendix H

PODOPHYLLUM EMODI (podophyllin)

cross reference: PODOPHYLLIN

Schedule 4

Schedule 3

Schedule 2

Appendix F, Part 3

Appendix H

PODOPHYLLUM PELTATUM (podophyllin)

cross reference: PODOPHYLLIN

Schedule 4

Schedule 3

Schedule 2

Appendix F, Part 3

Appendix H

SALICYLIC ACID

cross reference: CHOLINE SALICYLATE

Schedule 3

Appendix H

TIOCONAZOLE

Schedule 4

Schedule 3

Schedule 2

Appendix H

TRIAMCINOLONE

Schedule 4

Schedule 3

Schedule 2

Appendix F, Part 3, Part 2

Appendix H

Proposed implementation date:

1 February 2019

Reasons:
  • There is no potential for abuse, inappropriate use and/or diversion that may be exacerbated by advertising.
  • There are no potential interactions with the substances (drug-drug, drug-food) that require increased patient education to ensure safe use and therefore patient choice could be adversely influenced by advertising.
  • There are no additional risks associated with the dosage form that may impact on safe use that may be exacerbated by advertising.
  • There is no other information that may be relevant, for example the substance has sedating properties, or there are safer alternatives available and therefore patient choice could be adversely influenced by advertising.

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:

  • The outcome of the Appendix H review;
  • Consideration of the submissions in response to the public consultation and feedback from stakeholder workshops;
  • The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (2018) stating that Schedule 3 substances will be include in Appendix H unless it is determined that advertising is not appropriate for a particular substance; and
  • Section 52E of the Therapeutic Goods Act 1989, in particular (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.
Decision:

The delegate has also decided to refer the following substances to the ACMS for further advice:

  • Glyceryl trinitrate
  • Isosorbide dinitrate
Scheduling proposal and reasons for proposal

Advertisements to the public for therapeutic goods must not contain any reference to a substance included in Schedule 3 of the Poisons Standard[1], unless the substance is also listed in Appendix H of the Poisons Standard.[2]

Up until 2018, substances in Schedule 3 were not included in Appendix H, unless an adequate justification was presented as to the reasons for including the substance in Appendix H. Currently there are only 19 of 85 Schedule 3 substances included in Appendix H. As mentioned, the current Scheduling Policy Framework (2018) states that Schedule 3 substances will be included in Appendix H unless it is determined that advertising is not appropriate for a particular substance.

To facilitate the transition of substances to Appendix H, it was agreed that the current Schedule 3 substances would be considered via consultation, and specific rescheduling applications from individual stakeholders would not be required.

A consultation paper inviting comments on proposals to add a number of Schedule 3 substances to Appendix H of the Poisons Standard was published on the TGA website on 4 June 2018, and closed on 9 July 2018. This consultation was the culmination of input from stakeholders at targeted consultation activities held at the TGA in February and March of 2018, and led to the development of draft Guidelines for advertisements for medicines containing Schedule 3 Substances.


Footnotes

2.1. Crisaborole

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

2. New Chemical Entities (NCEs) - medicines for human therapeutic use

2.1. Crisaborole

Delegate's final decision
Final decision:

The delegate's final decision is to amend the Poisons Standard to include crisaborole in Schedule 4 as follows:

Schedule 4 - New Entry

CRISABOROLE

Index - New Entry

CRISABOROLE

Schedule 4

Proposed implementation date:

1 February 2019

Reasons:

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:

  1. the risks and benefits of the use of a substance:

    Crisaborole is a phosphodiesterase-4 (PDE-4) inhibitor and is developed for topical treatment of mild to moderate atopic dermatitis (AD). The specific mechanism(s) by which crisaborole exerts its therapeutic action is not well defined. In these uses the benefits are considered to outweigh risks at a population level (pending ACM review).

  2. the purposes for which a substance is to be used and the extent of use of a substance:

    Topical treatment of mild to moderate atopic dermatitis in patients 2 years of age and older.

  3. the toxicity of a substance:

    Crisaborole has its own distinct toxicities but these have been addressed within the benefit/risk consideration noted above.

  4. the dosage, formulation, labelling, packaging and presentation of a substance:

    The dose regimen, formulation, labelling, packaging and presentation of crisaborole have been considered and none of these aspects precludes scheduling of crisaborole as Schedule 4.

  5. the potential for abuse of a substance:

    Nil

  6. any other matters that the Secretary considers necessary to protect public health:

    Nil

Scheduling proposal

The delegate of the Secretary proposed to amend the Poisons Standard with respect to crisaborole.

Scheduling status

Crisaborole is not specifically scheduled and is not captured by any entry in the Poisons Standard.

Delegate's considerations

The delegate considered the following in regards to this scheduling:

  • Subsection 52E(1) of the Therapeutic Goods Act 1989;
  • The Scheduling Policy Framework (2018) scheduling factors;
  • The TGA evaluation report;
  • The advice of the Advisory Committee on Medicines;
  • The new drug application.

2.2. Brigatinib

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

2. New Chemical Entities – medicines for human therapeutic use

2.2. Brigatinib

Delegate's final decision
Final decision:

The delegate's final decision is to amend the Poisons Standard to include brigatinib in Schedule 4 as follows:

Schedule 4 - New Entry

BRIGATINIB

Index - New Entry

BRIGATINIB

Schedule 4

Proposed implementation date:

1 February 2019

Reasons:

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:

  1. the risks and benefits of the use of a substance:

    The risks and benefits of the medicine require assessment by a medical practitioner experienced in the treatment of the condition

  2. the purposes for which a substance is to be used and the extent of use of a substance:

    The diagnosis, management and monitoring of the clinical condition require expert medical assessment and review

  3. the toxicity of a substance:

    The safety profile of the medicine requires expert medical assessment and monitoring

  4. the dosage, formulation, labelling, packaging and presentation of a substance:

    Nil

  5. the potential for abuse of a substance:

    Nil

  6. any other matters that the Secretary considers necessary to protect public health:

    Nil

Applicant's scheduling proposal and reasons for proposal

The delegate of the Secretary proposed to amend the Poisons Standard with respect to brigatinib.

Current scheduling status

Brigatinib is not specifically scheduled and is not captured by any entry in the Poisons Standard.

Delegate's considerations

The delegate considered the following in regards to this scheduling:

  • Subsection 52E(1) of the Therapeutic Goods Act 1989;
  • The Scheduling Policy Framework (2018) scheduling factors;
  • Advice on the place in therapy of this NCE.

2.3. Lanadelumab

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

2. New Chemical Entities - medicines for human therapeutic use

2.3. Lanadelumab

Delegate's final decision
Final decision:

The delegate's final decision is to amend the Poisons Standard to include lanadelumab in Schedule 4 as follows:

Schedule 4 - New Entry

LANADELUMAB

Index - New Entry

LANADELUMAB

Schedule 4

Proposed implementation date:

1 February 2019

Reasons:

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:

  1. the risks and benefits of the use of a substance:

    It is a new chemical entity with no clinical and marketing experience in Australia.

  2. the purposes for which a substance is to be used and the extent of use of a substance:

    It is to be used for routine prevention of attacks of hereditary angioedema (HAE) in patients aged 12 years and older

  3. the toxicity of a substance:

    It can cause adverse events, such as hypersensitivity, injection site reactions, etc.

  4. the dosage, formulation, labelling, packaging and presentation of a substance:

    It is administered by subcutaneous injection

  5. the potential for abuse of a substance:

    Unlikely to be abused

  6. any other matters that the Secretary considers necessary to protect public health:

    Correct diagnosis of hereditary angioedema by a medical specialist is required prior to prescribing this product

Applicant's scheduling proposal and reasons for proposal

The delegate of the Secretary proposed to amend the Poisons Standard with respect to lanadelumab.

Current scheduling status

Lanadelumab is not specifically scheduled in the Poisons Standard, but as it is composed of a monoclonal antibody, it is captured by the Schedule 4 entry for monoclonal antibodies as follows:

Schedule 4

MONOCLONAL ANTIBODIES for therapeutic use except:

  1. in diagnostic test kits; or
  2. when separately specified in these Schedules.
Delegate's considerations

The delegate considered the following in regards to this scheduling:

  • Subsection 52E(1) of the Therapeutic Goods Act 1989;
  • The Scheduling Policy Framework (2018) scheduling factors;
  • Advice on the place in therapy of this NCE.

2.4. Romosozumab

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

2. New Chemical Entities - medicines for human therapeutic use

2.4. Romosozumab

Delegate's final decision
Final decision:

The delegate's final decision is to amend the Poisons Standard to include romosozumab in Schedule 4 as follows:

Schedule 4- New Entry

ROMOSOZUMAB

Index - New Entry

ROMOSOZUMAB

Schedule 4

Proposed implementation date:

1 February 2019

Reasons:

The matters under subsection 52E (1) of the Therapeutic Goods Act 1989 considered relevant by the delegate for the decision include:

  1. the risks and benefits of the use of a substance:
    • Romosozumab is a humanised monoclonal antibody that binds to and inhibits sclerostin
    • Treatment with romosozumab increases bone density and prevents fractures in patients with osteoporosis
    • Risks of treatment include hypocalcaemia (prevented by monitoring and concomitant use of calcium and vitamin D), osteonecrosis of the jaw
  2. the purposes for which a substance is to be used and the extent of use of a substance:
    • Romosozumab is to be used in the treatment of men and women with osteoporosis.
    • The diagnosis of osteoporosis requires an assessment by a medical officer. It is based on clinical history and examination, as well as diagnostic tests.
  3. the toxicity of a substance:
    • No concerning toxicity was identified in animal studies. Pregnancy category B3
  4. the dosage, formulation, labelling, packaging and presentation of a substance:
    • Romosozumab is administered as a subcutaneous injection. The formulation contains 105mg/1.17ml. The dosage is 210mg each month for 12 months
  5. the potential for abuse of a substance:

    Unlikely

  6. any other matters that the Secretary considers necessary to protect public health:

    Nil

Applicant's scheduling proposal and reasons for proposal

The delegate of the Secretary proposed to amend the Poisons Standard with respect to romosozumab.

Current scheduling status

Romosozumab is not specifically scheduled in the Poisons Standard, but as it is composed of a monoclonal antibody, it is captured by the Schedule 4 entry for monoclonal antibodies as follows:

Schedule 4

MONOCLONAL ANTIBODIES for therapeutic use except:

  1. in diagnostic test kits; or
  2. when separately specified in these Schedules.
Delegate's considerations

The delegate considered the following in regards to this scheduling:

  • Subsection 52E(1) of the Therapeutic Goods Act 1989;
  • The Scheduling Policy Framework (2018) scheduling factors;
  • The TGA clinical evaluation report;
  • Delegate's overview;
  • ACM advice.