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Notice of interim decisions on proposed amendments to the Poisons Standard - ACMS/ACCS/Joint ACMS-ACCS meetings, March 2020

Scheduling of chemicals and poisons

10 June 2020

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1.1. Rizatriptan

1 Interim decisions on proposed amendments referred to the Advisory Committee on Medicines Scheduling (ACMS #29 March 2020)

1.1. Interim decision in relation to rizatriptan

Note

New text is shown as green, larger font, with a horizontal line above it.

Deleted text is shown as red, smaller font, with a strikethrough.

Interim decision

Pursuant to regulation 42ZCZN of the Regulations, a Delegate of the Secretary has, in relation to the proposed amendment, made an interim decision to down-schedule rizatriptan from Schedule 4 to Schedule 3 by amending the current Poisons Standard as follows:

Schedule 4 - Amend Entry

RIZATRIPTAN except when included in Schedule 3.

Schedule 3 - New Entry

RIZATRIPTAN when in divided oral preparations containing 5 milligrams or less per dosage unit and when sold in a pack containing not more than 2 dosage units for the acute relief of migraine in patients who have a stable, well-established pattern of migraine symptoms.

Appendix H - New Entry

RIZATRIPTAN

Index - Amend Entry

RIZATRIPTAN

Schedule 4
Schedule 3
Appendix H

Proposed date of effect of the proposed amendment

1 February 2021

Reasons for the interim decision (including findings on material questions of fact)

In making this interim decision, the Delegate considered the following material:

  • The application to amend the current Poisons Standard with respect to rizatriptan;
  • Advisory Committee on Medicines Scheduling's advice;
  • The public submissions received in response to the pre-meeting consultation;
  • 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;
  • Scheduling handbook: Guidance for amending the Poisons Standard; and
  • Scheduling Policy Framework (SPF 2018).

Summary of ACMS advice/recommendations to the Delegate

The Committee recommended down-scheduling of rizatriptan to Schedule 3 in the Poisons Standard as follows:

Schedule 4 - Amend Entry

RIZATRIPTAN except when included in Schedule 3.

Schedule 3 - New Entry

RIZATRIPTAN when in divided oral preparations containing 5 milligrams or less per dosage unit and when sold in a pack containing not more than 2 dosage units for the acute relief of migraine in patients who have a stable, well-established pattern of migraine symptoms.

Appendix H - New Entry

RIZATRIPTAN

Index - Amend Entry

RIZATRIPTAN

Schedule 4
Schedule 3
Appendix H

In addition, the Committee recommended the Required Advisory Statements for Medicine Labels (RASML) statements align with the warning and advisory statements that are required and used in New Zealand. These include:

  • Chronic use can result in a rebound headache.
  • Do not use if you have an irregular heartbeat.
  • Do not use if you are allergic to sulfonamides.
  • Do not use with other migraine medications except on doctor's advice.
  • Do not use if you are pregnant except on doctor's advice.

The Committee did not recommend an implementation date to the delegate. The advice was for the TGA to consult with product sponsors on an appropriate implementation date taking into account the:

  • timeframes required for packaging and labelling changes to be made; and
  • proposed implementation dates for the related-triptans considered at the meeting of the ACMS in November 2019 (i.e. 1 February 2021), with a view to enacting the same date of effect for all three triptans.

Members agreed that the relevant matters under Section 52E(1) of the Therapeutic Goods Act 1989 included (a) the risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and 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 included:

  1. the risks and benefits of the use of a substance
    • Benefits
      • Rizatriptan provides effective treatment of acute migraine;
      • Well established safety profile when used as directed; and
      • Timely access for patients with confirmed migraine diagnosis may improve patient outcomes.
    • Risks
      • Frequent use of rizatriptan may result in medication overuse headache;
      • There are possible cerebral vascular side effects associated with rizatriptan as well as cardiovascular events;
      • Dizziness and somnolence were the most common drug related adverse effects;
      • Accidental and intentional overdose ;
      • Serotonin syndrome; and
      • Risk concerning potential delay in seeking medical advice.
  2. the purposes for which a substance is to be used and the extent of use of a substance
    • Acute migraine that has been previously diagnosed by a medical practitioner.
  3. the toxicity of a substance
    • Contraindications to use:
      • Uncontrolled hypertension;
      • Established coronary artery disease including ischaemic heart disease (IHD);
      • Signs and symptoms of IHD or Prinzmetal's angina;
      • History of stroke or transient ischaemic attack;
      • Peripheral vascular disease;
      • Cerebral vascular disease;
      • Basilar or hemiplegic migraine or ‘atypical' headache;
      • Using another triptan; and
      • Used an ergotamine type medication within 6 hours.
    • Drug interactions can occur between triptans and selective serotonin reuptake inhibitors (SSRI/ Monoamine oxidase inhibitors (MAOIs). This can lead to serotonin syndrome however the likelihood serotonin syndrome of low.
    • Adverse effects are typically mild in intensity and transient.
    • Most common adverse effects dizziness, somnolence, and asthenia/ fatigue.
    • No toxic dose has been established.
  4. the dosage, formulation, labelling, packaging and presentation of a substance
    • The recommended dose of rizatriptan is 10mg.
    • Doses should be separated by at least 2 hours, and no more than 30mg in any 24-hour period.
    • Formulations comes as tablets (orally disintegrating) or wafers:
      • Proposed pack size appropriate for intended use
      • Individual dose strength of 5mg of max. 10mg per pack appropriate dose for treatment of acute migraine attack
  5. the potential for abuse of a substance
    • Overuse of triptans may be associated with medication overuse headache.
  6. any other matters that the Secretary considers necessary to protect public health
    • Risk reduction can be further mitigated by pharmacist counselling and verification of diagnosis by a medical practitioner, if required.

Reasons for interim decision

I have made an interim decision to down-schedule rizatriptan to Schedule 3 of the Poison Standard with restrictions on the dosage and indication. The reasons for my decision are set out below.

In making this decision, I considered that rizatriptan is most effective when taken as soon as possible following the onset of a migraine. It is my view that timely access to rizatriptan is a critical factor to improving patient outcomes. Removing the requirement for, patients with a confirmed diagnosis of migraine, to obtain a prescription from a GP will promote prompt access rizatriptan.

I have determined that rizatriptan meets the Schedule 3 Scheduling Factors in the Scheduling Policy Framework (SPF) 2018. I took into account that there is the potential for harm and adverse effects if rizatriptan is used inappropriately. The use of rizatriptan at established therapeutic dosage levels may mask the symptoms or delay diagnosis of more serious conditions. I understand there is the potential for drug interactions between rizatriptan and other drugs. All these factors are consistent with a Schedule 3 classification.

I am not persuaded that consumers are able to safety self-manage the symptoms of migraine without pharmacist input. I find that pharmacist intervention is necessary as the clinical response to triptan medicines can vary. Pharmacist will exercise professional judgment on the migraine pattern of the presenting patient and if necessary, refer the patient for verification of diagnosis by a medical practitioner. On balance, I consider the risk profile of rizatriptan is well defined and the adverse effects, interactions and contraindications are known, identifiable and manageable by a pharmacist.

I have made a decision restrict Schedule 3 rizatriptan for migraine because this medicine is not effective for other types of headache.

The SPF 2018 provides that the advertising of medicines containing Schedule 3 substances should be permitted unless there was reason not to. In order for these medicines to be lawfully advertised, they need to be included in Appendix H of the Poisons Standard. Having considered the matters set out in the Guidelines for advertisements for medicines containing Schedule 3 substances, I am satisfied that there are no foreseeable potential impacts on public health that would preclude advertising rizatriptan directly to consumers and I have decided that it should be included in Appendix H.

I have made a decision not to include rizatriptan in Appendix M. I am satisfied that rizatriptan meets the Scheduling Factors under a Schedule 3 classification and that additional controls through inclusion in Appendix M are not necessary.

I have not made a decision on the RASML statements, as they are not relevant to the matters, which I must consider under section 52E of the Therapeutic Goods Act 1989. Accordingly, I have not given any weight to the ACMS recommendations insofar as it relates to the RASML statement and they were not material to my decision.

I agree with the Committee's finding that the relevant provisions of section 52E of the Therapeutic Goods Act 1989 are (a) the risks and benefits of the use of a substance; (b) the purpose for which a substance is to be used and the and 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.

Implementation date

I have decided on a 1 February 2021 implementation date to make rizatriptan available at the same time as sumatriptan, zolmitriptan, which were considered at the November 2019 ACMS meeting. In making this decision, I considered that the availability of a range of triptans in Schedule 3 is in the interest of promoting public health as not all patients will respond to any given triptan.

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