1.3 Mometasone

1 Final decisions made pursuant to regulation 42ZCZR - proposals referred to the November 209 Advisory Committee on Medicines Schedule (ACMS #28)

1.3. Final decision in relation to Mometasone

Final decision

Pursuant to regulation 42ZCZR of the Regulations, a Delegate of the Secretary has made a final decision to vary the interim decision and amend the current Poisons Standard in relation to mometasone as follows:

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

I have decided to vary the ACMS #26 interim decision not to down-schedule mometasone for dermal use from Schedule 4 to Schedule 3 and to introduce an actuation limit for mometasone. I find that mometasone for dermal use meets the Scheduling Factors for Schedule 3 without the requirement for an Appendix M entry; that the introduction of an actuation limit for intranasal mometasone in Schedule 2 is not required; and that in the interests of public safety, mometasone should not be included in Appendix H.

Material considered

In making my final decision, I have taken into account all available information including:

• The application to amend the current Poisons Standard with respect to mometasone;
• Advisory Committee on Medicines Scheduling's advice (ACMS #26 (March 2019) and ACMS #28 (November 2019));
• The public submissions received by the second closing date (ACMS #26);
• The public submissions received by the first closing date (ACMS #28);
• 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 Australian Health Ministers' Advisory Council's Scheduling Policy Framework (SPF 2018); and
• Scheduling Handbook (V 1.1, July 2019).

Reasons for the final decision

The reasons for my decision are set out below.

In my view, the relevant parts of the SPF 2018 are the Scheduling Factors for Schedule 3 and the criteria for inclusion of a medicine in Appendix M and Appendix H.

Topical corticosteroids (TCS) are important in the treatment of active corticosteroid-responsive dermatoses, including atopic dermatitis and psoriasis, which may have a fluctuating clinical course requiring access to treatment during periods of increased disease activity. Poor symptom control can result in significant impacts on a person's quality of life.

An application to down-schedule mometasone from Schedule 4 to Schedule 3 in 15 g packs, create a new entry in Appendix M and revise the wording of the Schedule 2 entry for inhaled mometasone to include a limit of 200 actuations per pack was first considered by the ACMS in March 2019.^[1] While the amendment to the Schedule 2 entry was supported by the Committee, down-scheduling to Schedule 3 and inclusion in Appendix M were not, in part because it was unclear what additional conditions or controls would be included in Appendix M. As a result, the Applicant was provided an opportunity to address the new Appendix M criteria published in the Scheduling Handbook^[2] and provided additional information, including addressing how inclusion of mometasone in Appendix M would mitigate the risks identified to support down-scheduling for consideration at the November 2019 ACMS meeting.

Public submissions were received opposing the down-scheduling of dermal mometasone to Schedule 3. These submissions cited mometasone's high potency and potential for increase in adverse reactions including corticosteroid-induced rosacea (perioral dermatitis) leading to skin atrophy and the theoretical risk of hypothalamic pituitary adrenal (HPA) suppression. In considering TCS, it is important to recognise that potency does not equate to toxicity. The criteria for defining topical corticosteroid potency is based upon vasoconstrictor and skin blanching effects, which are somewhat removed from the systemic corticosteroid effects that constitute the systemic risk. As raised in the public submissions, the higher the corticosteroid potency, the more likely it is that side effects will occur. However, in the case of mometasone, even though it is a potent Class IIT TSC, it has lower systemic toxicity than other TSC and has longer lasting effects. Potential risks associated with dermal mometasone are predominantly related to its inappropriate application such as to the face or for conditions in which topical corticosteroids broadly are contraindicated, not specifically mometasone. While there is a risk of perioral dermatitis and steroid rosacea if mometasone is applied inappropriately to the face, it is my view that there is insufficient evidence to suggest that Schedule 3 availability will necessarily increase this risk. Furthermore, there is no evidence to suggest that the theoretical potential risk of HPA suppression has been observed with topical mometasone, consistent with its low systemic bioavailability. HPA suppression is dependent upon exposure to supra-physiologic glucocorticoid concentrations for a sufficient duration. In combination with the inherently low systemic bioavailability of mometasone, the proposed restricted quantity able to be supplied under Schedule 3 discourages its use on large areas of the body and for long durations, limiting the attainment of the critical factors required to induce HPA suppression. I consider that patient education and the proposed product labelling 'Do not use on the face, or for more than 4 weeks without advice from a medical professional' are appropriate ways to mitigate these risks. In addition, the 15 g pack size limitation will also mean that patients with extensive disease requiring access to large quantities will continue to be appropriately managed by a general practitioner or dermatologist.

I have noted the concerns regarding the ability of pharmacists to perform a differential diagnosis in the supply of mometasone (e.g. fungal infections, herpes zoster infection etc.) as an impediment to down-scheduling. However, I am of the view that this consideration is not specific to mometasone and applies equally to the supply of other products that have been considered appropriate for down-scheduling from Schedule 4 to Schedule 2 or 3, including topical corticosteroids and anti-fungal products. Furthermore, pharmacists are already able to initiate treatment with Schedule 2 and Schedule 3 steroids based on their differential assessment of a patient's condition. There is no evidence to suggest that pharmacists are unable to recommend appropriate treatments and therefore, I do not consider this to present a barrier to down-scheduling.

In recognition that the use of mometasone at established therapeutic dosage levels may mask the symptoms or delay diagnosis of a serious condition, the proposal by the Applicant contains some caveats on use, and these are in the CMI - e.g. do not use around eyes, do not use on skin infections, check with a doctor etc. These label statements together with pharmacist oversight to monitor use and to provide education are consistent with and appropriate for a Schedule 3 entry and can effectively mitigate potential risks associated with down-scheduling.

Rescheduling of a substance into Schedule 3 may be facilitated by an entry in Appendix M of the Poisons Standard whereby additional controls or supply requirements are applied to enable substances to be provided by a pharmacist. However, the additional information provided by the Applicant addressing the new Schedule M criteria^[3] and public submissions questioning the robustness of Applicant's proposals have not been material to my decision. After taking into account the matters stated above, I find that the Scheduling Factors under Schedule 3 are met and that additional controls under Appendix M for mometasone are not required.

While not proposed by the Applicant, I have given consideration to inclusion of mometasone in Appendix H. Since 2018 the SPF and the Guidelines for advertisements for medicines containing Schedule 3 substances^[4] provide that in principle, all Schedule 3 substances are to be included in Appendix H unless it is determined that, in the interests of public health, it is not appropriate to allow a substance to be advertised directly to consumers. Given the potential for mometasone to be inappropriately used to treat conditions other than inflammatory conditions, I am of the view that there may only be limited additional benefit from the advertising of a more potent option and the choice of agent is best managed through consultation with the pharmacist. Consequently, I do not support an Appendix H entry for mometasone at this time.

In the matter of the introduction of an actuation limit for intranasal mometasone in Schedule 2, having had regard to the Committee's advice and the public submissions opposing the amendment, I am satisfied that an actuation limit is not required to ensure the medicine's continuing quality use. The introduction of an actuation limit for Schedule 2 mometasone is inconsistent with recent scheduling decisions from 2018^[5] and 2019^[6] that removed actuation limits from fluticasone and budesonide, aligning them to equivalent intranasal corticosteroids (including at that time, mometasone). In making these decisions, the Delegates determined that removal of the actuation limits to allow larger pack sizes to treat chronic conditions would be unlikely to impact the risk-benefit profiles of these substances.^[7],^[8] Given there are no safety signals warranting an amendment to the Schedule 2 entry in order to protect public health, it is my view that the introduction of an actuation limit for mometasone is not required and would impose an unnecessary regulatory burden on industry.

Summary of public submissions on the interim decision

Interim decision public submissions (ACMS #26)

Two (2) public submissions were received in response to the notice published under regulation 42ZCZP advising of the interim decision and invitation for further comment on substances referred to the March 2019 ACMS/ACCS meeting.^[9] Both public submissions were in opposition the interim decision.

Main points provided in opposition were:

• Mometasone for dermal use containing 0.1 % or less mometasone, in packs containing 15 g or less, substantially meets the Scheduling Factors for inclusion in Schedule 3.
• Pharmacists currently intervene in the supply of lower potency dermal corticosteroids that have very similar precautions and contraindications to higher potency corticosteroids.
• The introduction of an actuation limit for the current Schedule 2 entry conflicts with recent decisions for budesonide (2019) and fluticasone (2018) to remove actuation limits from other intranasal corticosteroids so that they could align with the (then) Schedule 2 entry for mometasone.
• Concerns with the diagnosis, management and monitoring of mometasone under Schedule 3 can be managed with an Appendix M entry that requires patients to have a medical diagnosis of their condition and a prescription specifying mometasone and that this must be reviewed by their medical practitioner every 6 months.
• Label warning statements and advice in the CMI not to use mometasone on the face or for more than two weeks without advice from a medical professional can help mitigate risks, such as corticosteroid-induced rosacea and skin atrophy, from the inappropriate application of mometasone to the face.

Pre-meeting public submissions (ACMS #28)

In response to the notice published under regulation 42ZCZK advising of the proposed amendment, six (6) submissions were received. Two (2) submissions supported the amendment, one (1) with caveats and four (4) submissions opposed the amendment.

The main points provided in support of the proposed amendment were:

• The substance meets the scheduling criteria for Schedule 3 substances.
• Suggest that it is not necessary to include the phrase "Specific pharmacist training on the provision of this medicine is required" in the Appendix M wording. Pharmacists already know about corticosteroid dermal preparations and the treatment of corticosteroid responsive skin conditions. Further, pharmacists are trained to differentiate between varied skin conditions and they are well aware of the pharmacology of topical corticosteroids. Skin conditions and their treatment are a staple part of a community pharmacist's work as they are often the first health professional that a patient will speak to. A community pharmacy is where most consumers will have their prescriptions dispensed.
• The Delegate and ACMS members are reminded that pharmacists under current scheduling arrangements are already able to initiate hydrocortisone treatment from their own assessment of a patient's condition that would require a similar approach in differential diagnosis when considering whether mometasone is appropriate for a patient's condition.
• A patient provided with this substance under the Schedule 3 Appendix M mechanism would already have consulted a medical practitioner regarding their condition and have trialled mometasone. They would have been counselled by the medical practitioner and the pharmacist when they have their first prescription dispensed. Pharmacist can verify that a patient has previously been prescribed this substance either by interviewing the patient or by consulting the patient's My Health Record or the pharmacy dispense records.
• There are no additional risks associated with the dosage form that may impact on safe use that will be exacerbated by advertising. Only patients that have a formal diagnosis and have previously used this substance will be eligible for access. Advertising will act as a reminder that they can access treatment for their condition should they experience a flare-up of their condition and cannot consult with their medical practitioner in a timely fashion.
• The Appendix M wording ensures that a patient must have previously been diagnosed with a dermal condition suitable for treatment with mometasone within the last 6 months. This requirement will ensure that there is no potential for inappropriate use or diversion that would be exacerbated by advertising.

The main points provided in support of the proposed amendment with caveats were:

• The proposed Appendix M controls appear logical and appropriate and the overall rescheduling proposal for mometasone is appropriate from a patient safety perspective. However, the Scheduling handbook outlines the expectation that an applicant seeking to reschedule a Schedule 4 substance to Schedule 3 with Appendix M conditions will conduct preliminary discussions with the pharmacy profession. In the absence of any discussion with XXX regarding the rescheduling to Scheduling 3 through Appendix M controls and the apparent lack of preparatory work on a suitable pharmacist training package, XXX is unable to support this proposal in its current form.
• Agree with the interim decision that mometasone should not be included in Appendix H.
• While supportive of the inclusion of an upper limit to the supply of Schedule 2, the conditions in the Schedule 2 entry include "... for the short term prophylaxis or treatment of allergic rhinitis for up to 6 months...". However, the TGA recently communicated (albeit in the context of the Appendix M criteria consultation) advice from States and Territories that "limits on frequency and duration of supply are not within their power to legislate". Therefore, clarification is sought on whether the reference to "for up to 6 months" is still appropriate for inclusion in the Schedule 2 entry of the Poisons Standard for mometasone, and if so, how this condition is expected to be fulfilled in practice.

The main points provided in opposition to the proposed amendment were:

• The proposed addition to Appendix M is entirely insufficient to satisfy the concerns outlined in the ACMS' interim decision. The proposed entry lacks detail on:
  • the proposed pharmacist training and what this entails;
  • the validation of the patient questionnaire;
  • the required records of diagnosis and therapeutic recommendation from the medical practitioner;
  • the mechanisms for patient follow up and management of adverse events; and
  • the tracking of clinical outcomes. There is no evidence to support this approach and it does not reflect good clinical practice.
• The XXX oppose the scheduling amendment on the terms of patient safety and in health care costs. The XXX supports the XXXXXXXXXXX XXXXXXX of XXXXXXXXXXXXXXX submission on the proposed amendments to mometasone^[10] and refers the Delegate to its own submission to the ACMS in January 2019 that further outlines the issues with down-scheduling mometasone.^[11]
• Mometasone is the most common cause of corticosteroid-induced rosacea (perioral dermatitis) and causes skin atrophy.^[12] Pharmacists do not have the medical training or expertise to know when to appropriately recommend mometasone to a patient, and rectifying adverse reactions requires medical practitioner expertise.
• There are already existing, effective, over the counter, low-potency topical steroid options and expanding access to higher potency steroids is fraught with negative consequences. XXX members are concerned that the number of adverse reactions will increase with the proposed changes. Further, there is a cost to the patient if mometasone is used inappropriately and they must pay for further treatment or medication such as antibiotics.
• The proposed amendment to the Schedule 2 entry that seeks to introduce a pack size limit of 200 actuations for intranasal mometasone is not supported. There was no transparency of the rationale for its inclusion for in the agenda nor explanation for the basis upon which public comment was sought.
• An actuation limit for intranasal mometasone should not be introduced after it has already been decided that similar limits are not needed for other equivalent intranasal corticosteroids and after it was determined that making budesonide available in a larger pack size was unlikely to impact the risk-benefit profile significantly.
• In recent Scheduling decisions it has decided that similar limits were not needed for other equivalent intranasal corticosteroids. The 1 February 2019 Poisons Standard removed the actuation limit of 200 actuations or less from the entry for budesonide in aqueous nasal sprays (see the Final Decision), on the basis that there was no actuation limit for other intranasal corticosteroids, i.e. mometasone. Similarly, a decision was made to remove the actuation limit for fluticasone, and this was included in the 1 October 2018 update to the Poisons Standard, (see the Final Decision).
• When deciding to remove the actuation limit for fluticasone, the Delegate's interim decisions stated that 'There is no difference in the risks of the substance by allowing more doses per pack'.^[13] Similarly, for budesonide, the Delegate stated that 'Removing the actuation limit will allow new larger pack sizes and provide a longer duration of treatment'; 'This change to the scheduling of budesonide in the Poisons Standard will align the Schedule 2 entry with other intranasal corticosteroids' and 'Making budesonide available in a larger pack size is unlikely to impact the risk-benefit profile significantly'.^[14]
• Both decisions (for budesonide and fluticasone) and the corresponding updates to the Poisons Standard were made to align both of these intranasal corticosteroid entries with that of intranasal. It is concerning that the current proposal is contradictory and does not provide a level playing field or consistency in approach for intranasal corticosteroids.

ACMS #28 Advice for the delegate's consideration

The Advisory Committee on Medicines Scheduling recommended that that the current Schedule 4 entry for mometasone be amended and that a new Schedule 3 entry be created in the Poisons Standard as follows:

The Committee also recommended an implementation date of 1 June 2020.

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

The Advisory Committee on Medicines Scheduling stated its reasons for its advice and recommendations as follows:

1. risks and benefits of the use of a substance:
   • Poorly controlled skin conditions can result in significant impairment of quality of life.
   • Easier access to limited amounts of a potent topical corticosteroid can assist suitable patients in managing these conditions.
   • Contraindications apply to topical corticosteroids as a class and not mometasone specifically and as such apply to other topical corticosteroids available without prescription.
   • Available evidence does not support a significant risk of skin atrophy.
   • Theoretical risk of suppression of the HPA axis. Clinical trials and extensive clinical experience with product supplied on prescription do not indicate that this a significant concern.
   • Risk of perioral dermatitis and rosacea if applied inappropriately to the face therefore pharmacist intervention is necessary.
2. the purpose for which a substance is to be used and the extent of use:
   • Used in the management of active corticosteroid-responsive dermatoses including atopic dermatitis.
3. the toxicity of the a substance:
   • The toxicity of mometasone meets the Schedule 3 factors
4. the dosage, formulation, labelling, packaging and presentation of a substance:
   • Limitation of Schedule 3 pack size to 15 g is a safety measure to limit the possibility of use on large areas of the body for prolonged durations.
   • The addition of reference to the actuations is an unnecessary change to Schedule 2 given other recent scheduling decisions for other intranasal corticosteroids
5. the potential for abuse of a substance:
   • Nil.
6. any other matters that the Secretary considers necessary to protect public health:
   • Larger pack sizes of mometasone will still be available as a Schedule 4 medicine.

Date of effect of the decision

1 June 2020

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