3.3 Clotrimazole

3 Interim decisions on proposed amendments referred to the Advisory Committee on Medicines Scheduling (ACMS #31, June 2020)

3.3 Interim decision in relation to clotrimazole

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 to clotrimazole.

Materials considered

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

• The application to amend the current Poisons Standard with respect to clotrimazole;
• The seven public submissions received in response to the pre-meeting consultation under regulation 42ZCZK of the Regulations;
• The advice received from the Meeting of the Advisory Committee on Medicines Scheduling (ACMS #31);
• Subsection 52E(1) 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 considered necessary to protect public health;
• The Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
• The Scheduling handbook: Guidance for amending the Poisons Standard.

Summary of ACMS advice to the Delegate

The Committee recommended that the current scheduling of clotrimazole in the Poisons Standard remains appropriate.

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 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 considered necessary to protect public health.

The reasons for the advice included:

a - the risks and benefits of the use of a substance:

• Risks
  • Well established safety profile with few risks from use.
• Benefits
  • Effective treatment of vulvovaginal candidiasis caused by Candida albicans.

b - the purposes for which a substance is to be used and the extent of use of a substance:

• For the treatment of vulvovaginal candidiasis caused by Candida albicans (clotrimazole 1% for vaginal use).

c - the toxicity of a substance:

• Clotrimazole is an imidazole derivative that has low levels of systemic absorption from vaginal administration.
• It is extensively metabolised in the liver to inactive compounds. No carcinogenicity or mutagenicity was observed in animal studies.
• Vaginal clotrimazole is generally well tolerated with the main reported adverse reactions being local irritation (e.g. burning, erythema). Hypersensitivity/allergic reactions are rare.
• Vaginal clotrimazole is considered safe to use in pregnancy (a 1-week course) and in breastfeeding.

d - the dosage, formulation, labelling, packaging and presentation of a substance:

• Clotrimazole 10mg/ml (1%) cream to be applied once daily for 6 days.
• Warning statements are already required for clotrimazole vaginal preparations. The effectiveness of the proposed packaging warning statement 'For women who have previously been diagnosed with vaginal thrush' is unclear given there is evidence that consumers do not read the package information and that reading the label does not improve the accuracy of self-diagnosis.

e - the potential for abuse of a substance:

• There is no evidence of dependence or abuse of clotrimazole vaginal preparations, however misuse due to misdiagnosis is probable.

f - any other matters considered necessary to protect public health:

• Repeated studies and clinical experience demonstrate that self-diagnosis is inaccurate. Self-misdiagnosis cannot be addressed by labelling, packaging, and the provision of other information alone.
• Use may delay diagnoses so does not meet Scheduling factors for Schedule 2.

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

I have made an interim decision not to amend the current Poisons Standard in relation to the clotrimazole, specifically not to down-scheduling clotrimazole in vaginal preparations from Schedule 3 to Schedule 2. The reasons for my decision are set out below.

It is my view that pharmacist intervention, currently in place, is the critical mitigating factor to ensure the quality use of clotrimazole 1% in preparations for vaginal use. Increased consumer availability as a Schedule 2 medicine would remove the opportunity for direct pharmacist consultation and increase the potential for harm to consumers.

In 2018, I made a final decision not to amend the current scheduling of clotrimazole, with the major risks identified as inaccurate self-diagnosis and delayed treatment if the product is used for vaginal infections not caused by Candida albicans. These previous concerns regarding misdiagnosis and delayed treatment where an individual self-diagnoses and self-selects a treatment for vaginal symptoms remain unchanged.

I disagree with the views expressed by the applicant, that clotrimazole meets the Schedule 2 Scheduling Factors outlined in the Scheduling Policy Framework 2018 (SPF 2018). Schedule 2 medicines are for minor ailments or symptoms that can easily be self-diagnosed by consumers and are unlikely to be confused with other more serious diseases or conditions. The TAFT project conducted by Tenni et al (2005) about treatment of vulvovaginal candidiasis (VVC) concluded that 'women who self-diagnose VVC do so poorly' and that 'approximately two thirds of patients who self-diagnose vaginal candidiasis are incorrect'^[1] . Another qualitative Australian study of bacterial vaginosis (BV) conducted by Bilardi et al (2016) found that individuals who experienced BV for the first time treated themselves for VVC and 'consequently did not seek medical assistance for up to a few weeks after symptoms first presented, however, sought treatment sooner with subsequent episodes'^[2].

I further find that the quality use of clotrimazole cannot be achieved by labelling, packaging and/or the provision of other information alone. The proposed warning statement 'For women who have previously been diagnosed with vaginal thrush' does not mitigate the risk of inaccurate self-diagnosis and subsequent delay in appropriate treatment.

Based on my assessment, I find that the net benefit associated with access to clotrimazole 1% in preparations for vaginal use as a Schedule 2 medicine is limited to convenience for consumers. Whilst clotrimazole 1% in preparations for vaginal use has a favourable safety profile, there is no compelling evidence to suggest that current access is inadequate. In my view, the benefit of convenience does not sufficiently outweigh the risk of harm associated with clotrimazole use set out above.

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.

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