1.2. Ondansetron

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

1.2. Interim decision in relation to ondansetron

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 not to amend the current Poisons Standard in relation ondansetron. Specifically, not to down-schedule ondansetron from Schedule 4 to Schedule 3 as proposed by the applicant.

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 ondansetron;
• 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; 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 that the current scheduling of ondansetron remains appropriate.

Members agreed that the relevant matters under 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; 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
   • The application proposed that ondansetron be down scheduled to enable provision of this product by a pharmacist to a person presenting with nausea and/or vomiting of any cause.
   • The application identified that the product was being widely used for indications outside of those approved by the TGA. The risks and benefits have not been assessed for any indications outside of those approved by the TGA and therefore the safety profile for use of this product for these conditions is not established.
   • Limited evidence presented for indications outside those already approved that require medical diagnosis.
2. the purposes for which a substance is to be used and the extent of use of a substance
   • Ondansetron is currently approved for the prevention of nausea and vomiting induced by cytotoxic therapy and radiotherapy and for the prevention of post-operative nausea and vomiting.
   • Outside of treating nausea and vomiting associated with chemotherapy and radiotherapy or following a surgical procedure, the use and safety of ondansetron has not been assessed.
3. the toxicity of a substance
   • The medication has potential to cause QTc interval prolongation in susceptible people, those with previous history, bradycardia, electrolyte imbalance, cardiac failure and those taking concomitant medicines which may cause QTc interval prolongation or electrolyte imbalance
   • Patients may complain of headaches and constipation.
   • Safety of ondansetron for use in human pregnancy has not been established as per TGA approved product information and as per therapeutic guidelines.
4. the dosage, formulation, labelling, packaging and presentation of a substance
   • Ondansetron is currently available as a tablet blister pack and solution for injection.
5. the potential for abuse of a substance
   • NIL
6. any other matters that the Secretary considers necessary to protect public health
   • When a product is used off-label the medical practitioner takes full medico-legal responsibility for any adverse outcomes that result from prescribing off-label to a patient.

Reasons for interim decision

I have made an interim decision not to amend the current Poisons Standard in relation ondansetron. My view is that the current scheduling of ondansetron is appropriate. The detailed reasons for my decision follow.

Ondansetron is currently approved for the prevention of nausea and vomiting induced by cytotoxic therapy and radiotherapy; and for the prevention of post-operative nausea and vomiting. In my reading, the evidence establishes that both of these indications require management by a medical practitioner. Having considered the Scheduling Policy Framework 2018 (SPF 2018), I find that the requirement for medical practitioner intervention is consistent with the Scheduling Factors under a Schedule 4 classification.

I have considered the views expressed in the public submissions and those of the applicant, suggesting that that down-scheduling ondansetron to Schedule 3 would enable pharmacists to supply ondansetron for off-label use as is currently being practiced by medical practitioners. In my opinion, the distinguishing feature between pharmacist and medical practitioners initiating off-label supply is the degree of patient follow-up. The risks associated with off-label prescribing of ondansetron by medical practitioners are managed with appropriate diagnosis, management or monitoring and patient follow-up. I am concerned that these protections, in particular the provision of patient follow-up, would not be adequately in place under the care of a pharmacist.

I have considered the safety alert on published by the Therapeutic Goods Administration (TGA) in 2012 regarding the use of ondansetron and the associated risk of QTc interval prolongation, which I find are relevant to my decision. It is my view that close monitoring by a medical practitioner is necessary in patients who have or may develop QTc interval prolongation, including those with electrolyte abnormalities, congestive cardiac failure, bradycardias or who take medicines.

The applicant has not presented, and I have not found, any compelling evidence that establishes pharmacist can supply odansetron to consumers outside the current approved indications with reasonable safety. In particular, I note with concern that the safety and effectiveness of ondansetron for the treatment of conditions outside of the approved indications have not been assessed by the TGA.

Having considered the need for medical practitioner oversight for the current approved indications and the risks to consumers associated with off-label in a pharmacy setting I am of the firm view that the current scheduling of odansetron is appropriate.

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 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; and (f) any other matters that the Secretary considers necessary to protect public health.