1

Welcome

The Chair opened the 55^th meeting at 9:30 am and welcomed members and guests.

2

Apologies

No apologies were received.

3

Confirmation of the minutes of the 54^th meeting held on Tuesday 24 November 2015

The minutes of the 54^th meeting were discussed and the following amendments were made:

1. The recommended classification wording of cyclizine (agenda item 8.2.1.d) did not clearly reflect the Committee's intent. It was noted that the New Zealand Gazette notice had captured the Committee's intent accurately.
   
   The recommendation for cyclizine should reflect the New Zealand Gazette notice, and read:
   1. Cyclizine; for oral use other than in medicines used for the treatment of anxiety or insomnia when sold in the manufacturer's original pack containing not more than six dosage units; for oral use in medicines used for the treatment of anxiety or insomnia when sold in the manufacturer's original pack containing not more than 10 dosage units.
2. The wording of dot point c in the discussion of agenda item 5.1.1 should be changed from:
   2. One member commented that there should be an emphasis on the unmet need; the proportion of women that aren't seeking effective contraceptives and are relying on the emergency contraceptive pill (ECP) or having an abortion to avoid unintended pregnancy; to
   3. One member commented that there should be an emphasis on the unmet need; the proportion of women that aren't seeking effective contraceptives and are relying on the emergency contraceptive pill (ECP) or terminations, to avoid or manage unintended pregnancies.
3. The recommendation wording for agenda item 6.1 should be changed from:
   4. The Committee encouraged Green Cross Healthcare Ltd to make another submission to extend the administration of influenza vaccine by a specially trained pharmacist who has completed a vaccinator course that is approved by the Ministry of Health to younger aged children; to
   5. The Committee discussed the possibility with Green Cross Healthcare Ltd of them making another submission to extend the administration of influenza vaccine by a specially trained pharmacist who has completed a vaccinator course that is approved by the Ministry of Health, to younger aged children.

The amended minutes were signed and dated by the Chair.

4

Declaration of conflicts of interest

The Conflict of Interest forms were returned to the Secretary.

The following conflicts of interest were declared:

1. Mrs A Shirtcliffe declared that she spoke with Ms C Walters regarding agenda item 8.2.1.d - Naloxone. Mrs Shirtcliffe explained that it was a general discussion around the formulations of naloxone (proprietary versus non-proprietary), dose forms, and information on efficacy. Ms Walters informed Mrs Shirtcliffe that she had been involved in the comment from the New Zealand Drug Foundation.

The Committee considered that this should not prevent Mrs Shirtcliffe from fully participating in the discussion or from contributing to the recommendation.

5

Matters arising

5.1

Objections to recommendations made at the 54^th meeting

5.1.1

Oral contraceptives – objection to the proposed reclassification from prescription medicine to restricted medicine (Royal New Zealand College of General Practitioners)

Purpose

This was an objection to the Committee's recommendation at the 54^th meeting to reclassify selected oral contraceptives (desogestrel, ethinylestradiol, norethisterone and levonorgestrel) from prescription medicine to restricted medicine, when sold in the manufacturer's original pack containing not more than six months' supply by a registered pharmacist who has successfully completed an approved training programme, when indicated for oral contraception in women who have previously been prescribed an oral contraceptive within the last 3 years from the date of an original medical practitioner's prescription.

The objection was upheld on the grounds of the process the Committee undertook to make their recommendation. Following the 53^rd meeting, Green Cross Healthcare Ltd objected to the Committee's recommendation that oral contraceptives should not be reclassified. In the objection, Green Cross Healthcare Ltd included an alternative proposal to the original submission. This alternative proposal was considered at the 54^th meeting, and the Committee made a recommendation based on this alternative proposal that selected oral contraceptives should be reclassified. However, at the time of its consideration, the Committee was under the impression that the alternative proposal had been made publicly available, which was incorrect. The Royal New Zealand College of General Practitioners (RNZCGP) objected on the grounds that proper process had not been followed as the alternative proposal had not been released to the public for consultation.

Background

At the 7^th meeting on 31 July and 1 August 1990, the Committee confirmed that desogestrel, ethinylestradiol, levonorgestrel and norethisterone were all classified as prescription medicines.

At the 14th meeting on 2 November 1994, the Committee considered the safety issues related to the use of oral contraceptives and decided to produce an extensive public consultation plan before making any recommendation on the reclassification of oral contraceptives.

At the 15^th meeting on 20 November 1995, the Committee recommended that further consideration of the reclassification of oral contraceptives should be deferred until the results of the several ongoing studies had been published and analysed. At the time several studies claimed that low dose oral contraceptive pills containing desogestrel and gestodene presented an increased risk of thromboembolism compared to other low dose oral contraceptive pills.

At the 51^st meeting on 8 April 2014, the Committee recommended that desogestrel, ethinylestradiol, levonorgestrel, and norethisterone should not be reclassified from their current schedule entries.

At the 53^rd meeting on 5 May 2015, Green Cross Healthcare Ltd made a submission to reclassify specific oral contraceptives from prescription medicines to restricted medicines to allow pharmacists who have completed a certified course approved by the Ministry of Health to prescribe to women who meet specific criteria. The submission included consideration of the specific points raised by the Committee at the 51^st meeting. Each concern raised by the Committee was claimed to be addressed. The submission argued that the model of care it proposed had now been reviewed by primary healthcare professionals and a more conservative approach had been taken.

The Committee recommended that desogestrel, ethinylestradiol, levonorgestrel, and norethisterone should not be reclassified from their current schedule entries.

The major reason it was declined was that the submission was not supported by medical representative bodies.

Green Cross Healthcare Ltd objected to the decision made at the 53^rd meeting. The original proposal was documented with the 53^rd meeting minutes. The grounds for the objection were:

• the criteria for reclassification were not followed
• support from medical representative bodies is not a prerequisite for reclassification
• minimising fragmentation of care is not a classification criterion
• access via other medical visits is not a classification criterion
• the Committee had not fully captured the benefit of increased access in preventing unintended pregnancy in its discussions
• the Royal Australian New Zealand College of Obstetrics and Gynaecology (RANZCOG) partially supported the proposal. It supported the availability of oral contraceptives only to women who had previously been prescribed oral contraceptives i.e. oral contraceptive naïve patients were excluded.

At the 54^th meeting on 24 November 2015, Green Cross Healthcare Ltd submitted a revised proposal for consideration if the objection was upheld. The alternative proposal requested the reclassification of desogestrel, ethinylestradiol, levonorgestrel, and norethisterone to restricted medicines when indicated for women who had been previously prescribed an oral contraceptive pill (OCP).

The alternative option proposed that oral contraceptives be available from trained pharmacists for women in the following five scenarios:

1. a NZ woman who has run out of her oral contraceptive
2. a woman visiting from overseas who has run out of her oral contraceptive
3. a woman receiving the emergency contraceptive pill who was a previous oral contraceptive user
4. a woman wanting to restart contraception who was a previous oral contraceptive user
5. a woman wanting post-partum contraception who was a previous oral contraception user.

The Committee made the following recommendations:

• That selected oral contraceptives (desogestrel, ethinylestradiol, norethisterone and levonorgestrel) should be reclassified as restricted medicines, when sold in the manufacturer's original pack containing not more than six months' supply by a registered pharmacist who has successfully completed a training programme (endorsed or accredited by an organisation to be confirmed), when indicated for oral contraception in women who have previously been prescribed an oral contraceptive within the last 3 years from the date of an original medical practitioner's prescription; and
• that Green Cross Healthcare Ltd should provide Medsafe with details of who will be responsible for accrediting the training programme and maintaining and enforcing the provisions under which a pharmacist with additional competencies could prescribe selected oral contraceptives; and
• that Green Cross Healthcare Ltd should update Medsafe of the changes required to the training and monitoring procedures to reflect the Committee's recommendations; and
• that market sales should be collected and analysed to monitor the success of the scheme in improving access to oral contraceptive pills.

Following the publication of the 54^th meeting minutes, the Committee received an objection from the RNZCGP. The objection was upheld on the grounds of a process issue, that the alternative proposal put forward by Green Cross Healthcare Ltd had not been available for public consultation as recorded in the minutes.

The RNZCGP provided an alternative proposal as part of its objection (the RNZCGP proposal). The details of the RNZCGP proposal were that:

1. the prescribing pharmacist should ensure that there has not been a change to the woman's health, or that of her close relatives
2. with any changes to the woman's health, or that of her relatives, she should be advised that the OCP may no longer be the appropriate contraceptive option for her
3. she has been prescribed that OCP within the past year
4. she has been reviewed by an authorised prescriber at least once since starting the OCP for the first time (i.e. OCP naïve women would need to have to been reviewed by a general practitioner as a follow up appointment since starting the OCP, before repeats can be provided without a prescription).

The previous submissions, alternative proposal, amended alternative proposal and the RNZCGP proposal requested the reclassification of selected oral contraceptives (desogestrel, ethinylestradiol, norethisterone and levonorgestrel), which are currently classified as follows:

Desogestrel, ethinylestradiol and norethisterone are classified as prescription medicines.

Levonorgestrel is currently classified as:

• prescription medicine; except when specified elsewhere in this Schedule; except in medicines for use as emergency post-coital contraception when sold by nurses recognised by their professional body as having competency in the field of sexual and reproductive health
• restricted medicine; in medicines for use as emergency post-coital contraception when in packs containing not more than 1.5 milligrams except when sold by nurses recognised by their professional body as having competency in the field of sexual and reproductive health.

Comments

A total of 10 comments regarding the proposed reclassification of selected oral contraceptives were received for this meeting. One comment requested clarification on the recommendation made at the 54^th meeting. Two comments were from individuals and organisations that did not support the amended alternative proposal. Five comments were from individuals and organisations that supported the amended alternative proposal, several of which proposed modifications. Two comments were from organisations that supported increased access to selected oral contraceptives (desogestrel, ethinylestradiol, norethisterone and levonorgestrel) but believed the amended alternative proposal did not capture this.

Discussion

The Chair introduced the objection with a summary of the record of events of the submissions and objections regarding the application for reclassification of selected oral contraceptives that was presented at the 51^st, 53^rd, 54^th and the current meeting. The Chair went on to compare the reclassification of selected oral contraceptives process with the standard process for a submission that has been unsuccessful for reclassification, where the applicant (if they wish to do so) resubmits a submission with amendments.

The Committee acknowledged the confusion generated from a submission for which deliberations have extended over four meetings, particularly when several objections had been made. The Committee noted the accumulation of information spread across a number of different documents and meetings. The Committee noted it would be prudent and avoid confusion, to consider the submission for the reclassification of selected oral contraceptives (desogestrel, ethinylestradiol, norethisterone and levonorgestrel) in its entirety, by combining all of the information accumulated so far.

The Committee noted that the majority of comments received with respect to the alternative proposal were regarding the amended alternative proposal that the Committee put forward and not the alternative proposal put forward by the applicant. The Chair took this opportunity to discuss the role of the Committee in that they are to assess the risk-benefit profile of a medicine against the criteria in the 'Medicines Classification Committee Handbook' (agenda item 5.2.2) for reclassification and that they are able to propose amendments to a proposal to improve its alignment with the handbook criteria. He also explained that it is the applicant’s role to communicate with stakeholders, not the Committee's responsibility. Thus, the Chair and the members stand by the recommendation made at the 55^th meeting.

The Committee noted that there were concerns surrounding the details of the accredited training programme. The concerns raised included

1. which organisation would be responsible for the training programme
2. whether pharmacists would be allowed to dispense any of the selected oral contraceptives to the woman who was previously prescribed an OCP (i.e. could pharmacists switch between selected oral contraceptives), or would pharmacists be limited to dispensing the oral contraceptive as previously prescribed.

The Committee compared the amended alternative proposal with the proposal put forward by the RNZCGP. They found various aspects of the two proposals warranted consideration. However, the Committee was concerned that the prolonged process this submission had followed meant that concerned parties remained confused about what was currently proposed. The Committee suggested that the submitters should submit a new, comprehensive proposal for consideration to ensure clarity, and that the proposed scheme provides assurance that the issues/ concerns raised had been considered.

Recommendation

The Committee invites Green Cross Healthcare Ltd and Natalie Gauld Ltd to make a new submission with complete background papers, and supporting documentation for consideration as an agenda item for the 57^th meeting, for the reclassification of selected oral contraceptives (desogestrel, ethinylestradiol, norethisterone and levonorgestrel) as restricted medicines. The Committee considers that if a new submission is made, it should address all of the concerns raised to date by the Committee, the public, healthcare professionals and medical bodies including those from the New Zealand Medical Association and the Royal New Zealand College of General Practitioners, and that the submission should be in accordance with the updated guidance document titled ‘How to change the legal classification of a medicine in New Zealand’ (agenda item 5.2.1).

The Committee suggests that Green Cross Healthcare Ltd and Natalie Gauld Ltd could consider collaborating with a New Zealand medical organisation to produce the new submission.

5.2

Matters arising for information

5.2.1

Updating the guidance document titled 'How to change the legal classification of a medicine in New Zealand' to include the publication of additional information submitted in objections

Purpose

The 'How to change a legal classification of a medicine in New Zealand' document (PDF 426 KB, 13 pages), provides guidance on the medicine classification process for the Committee members and members of the public.

A recent objection to a recommendation made by the Committee has identified an area of the process that could be more transparent. Objections are not published on the Medsafe website and therefore stakeholders have no opportunity to comment on the grounds for an objection. It has been noted that objections lodged by submitters may include a modification of the original submission and there is no opportunity for stakeholders to comment on any revisions prior to the meeting.

It is proposed to update the guidance document titled 'How to change the legal classification of a medicine in New Zealand' to include the process of publication of additional information submitted in objections.

Discussion

The Committee discussed a number of process issues that arose from an objection containing additional information including an alternative proposal.

The guidance document titled ‘How to change the legal classification of a medicine’ should be updated to reflect the following discussion points:

1. that the submission is fully accessible (including additional information, any appendices and the complete reference list), to the public to allow for a full consultation, and when a company requests to withhold data in an application from public disclosure, the Ministry of Health will balance 'public interest' in the submission against 'commercial sensitivity' when coming to its decision to withhold information or not
2. that it is made clear that the submission, including additional information, appendices and the complete reference list, should be subject to the provisions of the Official Information Act 1982 (OIA)
3. that objections will be published on the Medsafe website
4. that the applicant should write the submission with the view that it will be published on the Medsafe website
5. that an application for the reclassification of a medicine remains separate from an objection
6. that if an alternative proposal should arise from an objection, the applicant should communicate with the Secretariat and follow the agenda timelines. The applicant should understand that consideration of an alternative proposal may not occur until the following meeting to allow for a full consultation to take place
7. the Committee also considered updating the criteria referred to when considering a medicine reclassification.

Recommendation

That the guidance document titled ‘How to change the legal classification of a medicine in New Zealand’ should be changed to reflect the suggestions made by the Committee and consulted on as an agenda item for the 57^th meeting.

5.2.2

Updating the Medicines Classification Committee Handbook to include a Deputy Chair

Purpose

The Medicines Classification Committee Handbook is a document for members to refer to regarding their responsibilities and meeting protocol.

It is proposed to update the Medicines Classification Committee Handbook to include a Deputy Chair (the second officer of the Ministry of Health) for times when the Chair is unavailable.

Discussion

The Committee discussed the appointment of a Deputy Chair and agreed that the person should be the other Ministry of Health representative due to the current framework.

Recommendation

That the second member of the Ministry of Health should be appointed as Deputy Chair for when the Chair is unavailable.

5.2.3

Review of tramadol and codeine reclassification

Discussion

The Committee noted that the Australian Committee on Medicine Scheduling (ACMS) discussed the reclassification of codeine and tramadol at its meeting in March 2016, however no recommendations or outcomes had been made available at the time of the 55^th meeting.

The Committee noted that the Expert Advisory Committee on Drugs (EACD) had recently considered tramadol. They considered that the outcomes from the EACD meeting on tramadol would be useful information.

Recommendation

That the Committee will review the outcomes of the ACMS meeting on tramadol and codeine once the Secretariat has received the information. The Committee will consider harmonising with the Australian Schedule and the Secretariat will add its recommendation to the agenda of the subsequent meeting to allow for a full consultation.

The Committee will also consider the outcomes of the EACD meeting on tramadol, when determining whether further classification activity is required.

5.2.4

Change in classification wording of benzydamine – change in classification wording of benzydamine from general sales medicine for topical and external use to general sales medicine for oral mucosal and topical use

Background

At the 54^th meeting, the Committee made the recommendation that the classification of benzydamine change from:

• general sale; for dermal use.
• pharmacy-only; for external use except for dermal use.
• prescription; for internal use, to

• general sale; for topical or external us
• prescription; for internal use except for topical or external use.

The definition of external use of medicines in the Medicines Regulations 1984 (the Regulations) is:

in relation to any medicine or related product, means for application to the anal canal, ear, eye, mucosa of the mouth, nose, skin, teeth, throat, or vagina, where local action only is required and where extensive systemic absorption will not occur; but nothing in these regulations relating to medicines or related products intended for external use shall apply to nasal drops, nasal inhalations, nasal sprays, teething applications, throat lozenges, throat pastilles, throat sprays, or throat tablets.

Medsafe amended the wording of the proposed classification of benzydamine to incorporate what it believes the MCC intended to capture in its recommendation, which was to include throat lozenges and throat sprays as general sales medicines.

The classification of benzydamine was included in the New Zealand Gazette as:

• prescription medicine; for internal use except for oral mucosal or topical use
• general sales medicine; for oral mucosal or topical use.

Discussion

The Committee discussed the definition of external use of medicines as defined in the Regulations.

The Committee accepted that the change in classification wording of benzydamine reflected the recommendation made at the 54^th meeting, and that the change delivered the same messages and the same risk-benefit profile as what the Committee had intended.

The Committee unanimously agreed to accept the change in classification wording of benzydamine.

Recommendation

That no recommendation was required.

5.2.5

Classification wording of lignocaine – proposed amendment to classification wording

Purpose

Medsafe has noted that the use of the term 'external use' in the general sale classification of lignocaine unintentionally excludes lignocaine throat sprays.

Medsafe proposes amending the classification from:

• General sales; for external use in medicines containing 2% or less; in throat lozenges containing 30 milligrams or less per dose form, to

• General sales; for external use and in throat sprays in medicines containing 2% or less; in throat lozenges in medicines containing 30 milligrams or less per dose form

Discussion

The Committee noted that the proposed amendment utilised the same arguments as agenda item 5.2.4 – change in classification wording of benzydamine.

The Committee accepted that the decision to change the general sales medicine classification wording of lignocaine reflects the definition of external as defined by the Medicines Regulations 1984.

Recommendation

That the general sales classification wording of lignocaine should be amended to:

• General sales; for external use and in throat sprays in medicines containing 2% or less; in throat lozenges in medicines containing 30 milligrams or less per dose form

5.2.6

Review of paracetamol pack size

The Chair updated the Committee that the review of paracetamol pack size was still in progress, and should be available for the next meeting.

6

Submissions for reclassification

6.1

Alcohol >20% – proposed extension of the general sales medicine classification of alcohol >20% to have the additional requirement of the product being wall mounted (Te Arai BioFarma Ltd)

Purpose

This was a company submission by Te Arai BioFarma Ltd, for the proposed amendment of the general sales medicine classification of alcohol >20%, for the prevention of spread of microorganisms, to have the additional requirement of the product being wall mounted.

Discussion

The Committee discussed the intention of Section 58A of the Regulations. The Committee interpreted the Regulations to mean that hand sanitisers containing alcohol >20% for the prevention of the spread of microorganisms in the general populous were not medicines.

(1) The following classes of substances are not medicines or related products for the purpose of the Act:

(2) The procedures referred to in subclause (1)(e)(iii)(B) are —

The Committee therefore did not consider the submission due to the remit was outside of the Committee’s terms of reference.

Recommendation

That the Committee should not consider the submission which requested to extend the general sales medicine classification of alcohol >20% in hand sanitisers to have the additional requirement of being wall mounted as these products are not considered to be medicines and therefore are outside the terms of reference of the Committee.

6.2

Adapalene – proposed reclassification from prescription medicine to prescription medicine except in medicines containing not more than 1 mg/g and when supplied in a pack of not more than 30 g by a pharmacist (Green Cross Healthcare Ltd and Natalie Gauld Ltd)

The submitters observed the discussion but left the meeting room before a final recommendation was made.

Purpose

This was a company submission for the reclassification of adapalene from prescription medicine to prescription medicine except in medicines containing not more than 1 mg/g and when supplied in a pack of not more than 30 g by a pharmacist when indicated for the treatment of acne vulgaris.

Background

At the 11^th meeting on Tuesday 29 June 1993, the Committee classified adapalene as a prescription medicine.

Adapalene is classified as a prescription medicine in New Zealand.

Comments

A total of five comments were received on the proposed reclassification of adapalene. Two comments supported the proposal whilst three comments did not support the proposed reclassification of adapalene.

Discussion

The risk-benefit assessment of adapalene focused on:

1. the toxicology and potential harm of adapalene use in pregnant women;
   1. the Committee noted that the pharmacokinetics of adapalene reduced the risks of harm in pregnant women
   2. the Committee noted that a clinical conversation provided in Appendix D stated that adapalene use should exclude use by pregnant women
   3. the Committee noted that there was insufficient data to suggest the side effects were more severe in pregnant women
2. the potential side effect of developing a photosensitivity, though this can be managed with the right support and guidance
3. education on use, contraindications and recognising conditions concerned.
   
   The Committee was updated on the availability of adapalene in Germany, Singapore and United States:
   1. it was noted that Singapore had recently approved adapalene availability at the pharmacy level
   2. it was noted that the grounds for which the German Authorities rejected the reclassification of adapalene were that there was no German equivalent classification sought (restricted medicine)
   3. the American Food and Drug Administration (FDA) were reviewing ab application, and it was noted that the American Human Drug Advisory Committee on medicines reclassification fully supported the reclassification of adapalene.
   The Committee sought clarification on:
4. the comparative side effects of adapalene compared to the side effects profile of benzoyl peroxide 10% (prescription) and to benzoyl peroxide 5% (general sale).
   1. A submitter noted that the statement made about the tolerability of adapalene was not supported by data.
5. An article referenced in the submission that did not address the complete issue of access (Purvis D, Robinson E and Watson D. Acne prevalence in secondary school students and their perceived difficulty in accessing acne treatment. The New Zealand Medical Journal. 2004, 117(1200)).
   1. A conclusion drawn from the article published in 2004 stated there was an increase in barriers to adapalene access. However, even though 80% of those surveyed indicated they did not have a problem with access, the 20% that did have a problem, had identified cost as a major access barrier.
   2. The Committee was curious as to why the application had not addressed this need.
   3. In response, the applicant shared they had received feedback from a dermatologist who did not consider this to be an issue.
6. The request for the 'prescription medicine except' classification versus ‘restricted medicine’ classification
   1. Several members indicated that they preferred the restricted medicine classification as it provided safe guards that ensured the patient received information on adapalene.

The Committee appreciated the information on teratogenicity as sought from Christchurch Drug Information Centre.

Overall, the Committee considered that there were no outstanding risks that should prevent the availability of adapalene as a 'prescription medicine except' classification. However, the Committee's discussion focused on the classification sought in comparison to a restricted medicine classification.

Recommendation

That adapalene should be reclassified as prescription medicine except in medicines containing not more than 1 mg/g and when supplied by a pharmacist in a pack of not more than 30 g.

That the above recommendation should be referred to the Australian Delegate of the Australian Committee on Medicine Scheduling.

6.3

Albendazole – proposed reclassification from prescription medicine to pharmacy-only medicine (Te Arai BioFarma Ltd)

This submission was withdrawn by the applicant prior to the meeting.

6.4

Loratadine – proposed extension of the current general sales classification to include an increased pack size (Claratyne 10 mg tablets, Bayer Healthcare Ltd)

Purpose

This was a company submission for the reclassification of loratadine to increase the general sales medicines pack size of loratadine from five days’ supply to 10 days’ supply for the treatment of allergic rhinitis.

Background

At the 5^th meeting on 11 November 1986, the Committee reviewed a proposal requesting a pharmacy-only medicine classification of loratadine. The Committee deferred making a decision until the Medicines Assessment Advisory Committee (MAAC) had made a recommendation on an application on loratadine up for consideration.

At the 6^th meeting on 10 March 1987, the Committee noted that the MAAC had requested additional information and deferred making a decision.

At the 7^th meeting on 31 July and 1 August 1990, loratadine was classified as a pharmacy-only medicine.

At the 10^th meeting on 11 November 1992, the decision to recommend loratadine as a general sales medicine was postponed due to the reversal of a recommendation the Committee made on terfenadine; where the general sales medicine classification of terfenadine was reverted back to pharmacy-only medicine due to the information about possible cardiac effects.

At the 11^th meeting on 29 June 1993, the Committee decided that non-sedating antihistamines such as loratadine should not be reclassified from pharmacy-only to general sales medicine. The Committee had also received a letter from the Medicines Adverse Reaction Committee (MARC) to consider reclassifying terfenadine, astemizole and loratadine as restricted medicines due to concerns about cardiac effects. As there were no reports of cardiac arrhythmias with loratadine use it was decided not to reclassify loratadine as a restricted medicine.

At the 12^th meeting on 25 November 1993, the Committee recommended to keep the pharmacy-only medicine classification of terfenadine, astemizole and loratadine as there was still insufficient evidence for them to consider altering the classification. They recommended that loratadine should be tabled for reclassification when new information became available.

At the 17^th meeting on 15 May 1997, the Committee noted correspondence from the MARC, that they had produced no further information that would result in them requesting the MCC to reconsider reclassifying loratadine as a restricted medicine.

At the 22^nd meeting on 10 November 1999, the Committee decided to harmonise with the Australian Schedule, that loratadine should be classified as a:

• prescription medicine except when specified elsewhere in the Schedule, and
• that the pharmacy-only medicine entry classification should be amended to read pharmacy-only medicine; for oral use, except when a prescription medicine.

At the 49^th meeting on 19 June 2013, the Committee noted that the Australian Delegate had made the following amendment to the classification of loratadine:

That loratadine should be reclassified from pharmacy-only medicine to general sales medicine when in divided forms for oral use containing 10 mg or less per dose in packs containing no more than 5 days’ supply for the treatment of seasonal allergic rhinitis.

The current classification of loratadine is:

• prescription medicine; except for oral use
• pharmacy-only medicine; for oral use except in divided solid dosage forms for oral use containing 10 milligrams or less per dose form for the treatment of seasonal rhinitis when sold in the manufacturer's original pack containing not more than 5 days' supply
• general sales medicine; in divided solid dosage forms for oral use containing 10 milligrams or less per dose form for the treatment of seasonal allergic rhinitis when sold in the manufacturer's original pack containing not more than 5 days' supply

Comments

Three comments were received opposing the extension of the general sales medicine classification of loratadine to increase the pack size to 10 days’ supply.

Discussion

The Committee's discussion on the proposed increase in pack size of the general sales medicine classification of loratadine was attentive to the following topics:

1. appropriate pack size versus convenience of buying multiple packs
   1. the Committee noted that allergic rhinitis would not completely resolve within five days, and
   2. that if the user continued to have symptoms after ten days' time that the user can and should seek medical attention
   3. the Committee did not consider that there was not a significant risk in increasing the pack size from 5 days' supply to 10 days' supply.
2. the article by Poluzzi E, Raschi E, Godman B, Koci A, Moretti U, Kalaba M, Bjorn Wettermark B, Sturkenboom M, De Ponti F. Pro-Arrhythmic Potential of Oral Antihistamines. PLoS ONE. 2015, 10(3).
   1. the Committee was not convinced that there was a level of concern surrounding loratadine use and QT syndrome
   2. the Committee was more concerned of the totality of medicines the patient was taking, whether any of the other medicines had a medical implication and whether they were taking medicines that impact on the QT interval.
3. dosage for children under 12 years of age
   1. the Committee was concerned that there was no differentiation of access as a general sales medicine between children under the age of 12 and adult
   2. the Committee noted that children aged between 2 and 12 and weighing >30 kg, are given a full adult dose (10 mg loratadine), and children within this age bracket weighing <30 kg are given 5 mg loratadine (half the dose)
   3. the Chair stated that the classification statement could not allow for such distinction and that excluding the availability of 10 days' supply packs for children would be controlled by Medsafe at the approval process.

Recommendation

That the general sales classification of loratadine should be amended to include an increased pack size of 10 days’ supply.

That Medsafe should not approve applications for 10 days’ supply of loratadine as a general sales medicine, when indicated for the treatment of allergic rhinitis in children under the age of 12.

6.5

Change in classification wording of lansoprazole, promethazine, sumatriptan, ibuprofen, omeprazole, pantoprazole, opium, phlocodine and ranitidine (Pharmaceutical Society of New Zealand)

The submitters observed the discussion but left the meeting room before a final recommendation was made.

Background

The Pharmaceutical Society of New Zealand (PSNZ) has made a submission to change the classification wording of lansoprazole, promethazine, sumatriptan, ibuprofen, omeprazole, pantoprazole, opium, phlocodine and ranitidine to remove the references that only approved or manufacturer's original packs may be supplied as restricted or pharmacy-only medicines. The Society's justification was that Section 23 of the Medicines Regulations 1984 (the Regulations) provides specific labelling criteria of medicines sold by an authorised prescriber or pharmacist for the purposes of repackaging medicines. The label of the repackaged medicine would not need to comply with the requirements of Section 13: Labelling of medicines, Section 16(1): Principal display panel or Section 22: Warning statements for medicines and related products.

The relevant excerpt of the Regulations is provided below:

Section 23: Labels on containers of medicines sold by authorised prescribers or pharmacists. It shall not be necessary to comply with the requirements of regulation 13 or regulation 16(1) or regulation 22 in respect of any label on a container of a medicine that is packed, supplied, or sold by an authorised prescriber or a pharmacist with reference to the needs of a particular patient or (as the case may be) a particular customer, if the label contains the following:

1. the name of, or a description of the nature of, the contents; and
2. the name of the patient; and
3. the name and address of the seller; and
4. in the case of a medicine for internal use, the dose and frequency of dose; and
5. in the case of a medicine for external use, a statement of the directions for use and frequency of use, and one or other of the following statements, or words of similar meaning:
6. "Caution: Not To Be Taken", or "For External Use Only"; and
7. a unique identifying number or code for the prescription or record of supply; and
8. the date on which the medicine was packed, sold, or supplied.

The proposal requested the following changes to the classification wording:

Comments

Four comments were received on the proposed change in classification wording of lansoprazole, promethazine, sumatriptan, ibuprofen, omeprazole, pantoprazole, opium, phlocodine and ranitidine. One comment supported the proposal, and three comments received were from organisations that opposed the proposal.

Discussion

The proposed change in classification wording of lansoprazole, promethazine, sumatriptan, ibuprofen, omeprazole, pantoprazole, opium, phlocodine and ranitidine to remove the reference that only approved or manufacturer's original packs may be supplied would allow pharmacists to repackage these restricted medicines into smaller pack sizes.

The proposal would accommodate the following scenarios:

1. breaking down larger packs when smaller pack sizes are not available
2. providing a patient who has a health need with the required amount of medicine and limiting the cost to this amount
3. providing limited amounts of medicines such as controlled drugs for safety reasons.

The Committtee was informed that:

1. this process is already taking place with some medicines but that this happens infrequently
2. there is no commercial gain
3. there are more safe guards, to be made by pharmacies, when selling a restricted medicine in this manner than a consumer purchasing a pharmacy-only medicine off the shelf
4. there are safe guards, standardisation, uniformity and traceability processes in place as pharmacists who repackage medicines are bound to New Zealand Standards
5. these processes are auditable by Medicines Control.

The Committee noted that these changes would allow pharmacists to breakdown and repackage prescription medicines to sell over the counter. This would include medicines purchased from wholesalers at prices achieved by PHARMAC agreements.

The main concern raised by the Committee surrounded the significant decrease in written information that would follow adoption of this recommendation.

1. The Chair made the comment that many of the restricted medicines in question were reclassified due to the provision that the whole pack had to be provided, which includes warning statements and written information the patient can refer back to
2. Several members were concerned that approval of this application would lead to repackaging of medicines to plain boxes with limited or no warning statements and that the expectation of the dispensing pharmacist to verbally communicate information to the patient could lead to missing or miscommunication of information
3. The Committee was curious to know how repackaging of medicines would impact pharmaceutical companies.

Recommendation

That the submission for the change in classification wording of lansoprazole, promethazine, sumatriptan, ibuprofen, omeprazole, pantoprazole, opium, phlocodine and ranitidine requires further consideration.

That the Committee should defer making a decision until further information is provided on how the submitter would address information requirements and how the submitter would address keeping labels up to date as new information on adverse effects to a medicine is published internationally.

7

New medicines for classification

The following new chemical entities were submitted to the Committee for classification.

7.1

New chemical entities that are not yet classified in New Zealand

7.1.a

Cobimetinib

Cobimetinib is a MEK1 and MEK2 tyrosine-theonine kinase inhibitor that is indicated for use in combination with vemurafenib (Zelboraf) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

The inhibition of MEK1 and MEK2 tyrosine-theonine kinases disrupts a key signalling pathway, mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (MEK) that regulates cell proliferation, cell cycle regulation, cell survival, angiogenesis and cell mitigation.

Cobimetinib is not classified in Australia.

Recommendation

That cobimetinib should be classified as a prescription medicine.

7.1.b

Ramucirumab

Ramucirumab is a human IgG1 monoclonal antibody which is indicated for the treatment of advanced gastric cancer or gastro-oesophageal junction adenocarcinoma after or prior to chemotherapy.

Ramucirumab works by specifically binding to vascular endothelial growth factor (VEGF) receptor 2, the key mediator of VEGF induced angiogenesis, and inhibiting the binding of VEGF-A, VEGF-C and VEGF-D. As a result, ramucirumab inhibits ligand stimulated activation of VEGF receptor 2 and its downstream signalling components including p44/p42 mitogen-activated protein kinases, neutralising ligand-induced proliferation and migration of human endothelial cells.

Ramucirumab is not classified in Australia.

Recommendation

That ramucirumab should be classified as a prescription medicine.

7.1.c

Sacubitril

Sacubitril/valsartan under the trade name Entresto is indicated in adults for the treatment of chronic heart failure (NYHA Class II-IV) with reduced ejection fraction.

Together, sacubitril and valsartan is a novel angiotensin receptor neprilysin inhibitor (ARNI). It works by simultaneously inhibiting neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and by inhibiting the angiotensin II type-1 (AT1) receptor via valsartan.

Both sacubitril and valsartan are classified as a prescription medicines in Australia. Only sacubitril requires classification in New Zealand as valsartan is already classified as a prescription medicine.

Recommendation

That sacubitril should be classified as prescription medicine.

8

Harmonisation of the New Zealand and Australian schedules

8.1

New chemical entities which are not yet classified in New Zealand

8.2

Decisions by the Secretary to the Department of Health and Aging in Australia (or the Secretary's Delegate)

The Committee noted that the Delegate had also made the following amendments to the Standard for the Uniform Scheduling of Medicines and Poisons:

8.2.1

Decisions by the Delegate - November 2015

a. Esomeprazole

The ACMS recommended that esomeprazole in oral preparations containing 20 mg or less per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than seven days' supply, be down-scheduled from restricted (Schedule 3) medicine to pharmacy-only (Schedule 2) medicine.

The ACMS also recommended to the delegate that consideration be given to down-scheduling the other OTC proton pump inhibitors (PPIs) (lansoprazole, omeprazole and rabeprazole) from restricted (Schedule 3) medicine to pharmacy-only (Schedule 2) medicine in packs containing not more than seven day' supply.

The ACMS had based its recommendations on the following:

• esomeprazole is a safe and effective first-line treatment for consumers with frequent symptoms of gastro-oesophageal reflux disease
• heartburn and other symptoms of gastro-oesophageal reflux disease are common
• esomeprazole has very low toxicity with short-term use
• the proposed pharmacy-only (Schedule 2) pack size (seven days' supply), labelling (including Required Advisory Statements for Medicine Labels (RASML) warning statements) and provision of consumer medicine information will help ensure appropriate use of esomeprazole as a pharmacy-only (Schedule 2) medicine
• the current RASML label warnings for all OTC PPIs would apply to esomeprazole as a pharmacy-only (Schedule 2) medicine or as a restricted (Schedule 3) medicine
• esomeprazole may be more effective in the treatment of gastro oesophageal reflux disease than ranitidine which is currently available as an unscheduled medicine (seven days' supply) and as a pharmacy-only (Schedule 2) medicine (14 days' supply).

The Committee considered harmonising with the above classification, and recommended that esomeprazole should be classified in the same manner as omeprazole.

Recommendation

That esomeprazole in divided solid dosage forms for oral use containing 20 mg or less with a maximum daily dose of 20 mg for the short-term symptomatic relief of gastro-oesophageal reflux-like symptoms in sufferers aged 18 years and over when sold in the manufacturer's original pack containing not more than seven dosage units should be a pharmacy-only medicine.

That the label statement on the manufacturer's original pack should include the following warnings:

• Do not use if you are experiencing weight loss, persistent regurgitation of food or vomiting, difficulty swallowing or symptoms of gastro-intestinal bleeding, except on medical advice.
• This product is for temporary use only. [or] For short term use only.
• Do not use this medicine for any purpose other than that specified on the pack, except on doctor's advice.
• Do not use if you are pregnant except on the advice of a healthcare professional.
• Consult a doctor if symptoms/condition persist(s), worsens or recur.
• Consult a doctor if new or additional symptoms occur.

b. Hydrocortisone

The ACMS recommended that hydrocortisone 1% when combined with antifungal substances for dermal use in packs containing 15 g or less be down-scheduled from restricted (Schedule 3) medicine to pharmacy-only (Schedule 2) medicine - specifically, hydrocortisone and hydrocortisone acetate should be included in Schedule 2 in preparations for dermal use containing 1% or less of hydrocortisone when combined with an antifungal substance (and no other therapeutically active substance), under the following conditions:

• in packs containing 15 g or less; and
• for the treatment of tinea (tinea pedis, tinea cruris, tinea corporis) and fungal skin infections; and
• not labelled for the treatment of children under 12 years.

The ACMS had based its recommendations on the following:

• hydrocortisone 1% is more effective than hydrocortisone 0.5% and the overall adverse reports are similar. The 1% strength does not produce more severe adverse reactions.
• tinea and fungal infections are common. Itching and inflammation may occur with these infections.
• the overall risk of adverse events from topical hydrocortisone use is very small and the relative risk between the 0.5% and 1% strengths are hardly distinguishable. It has a good safety profile in short term dermal use.
• the proposed 15 g pack size minimises duration of use and the proposed labelling reduces the risk of inappropriate use.
• providing easier access to a more effective product may be beneficial for consumers.

The Committee considered harmonising with the above classification.

A brief history of Australian classification events on hydrocortisone was provided to the Committee.

1. In 1999, 1% hydrocortisone and 0.5% hydrocortisone were classified as a restricted (Schedule 3) medicine and pharmacy-only (Schedule 2) medicine, respectively.
2. In 2007, the ACMS reclassified hydrocortisone in combination with a local anaesthetic for rectal use to harmonise with the New Zealand Schedule.
3. In 2013, the ACMS declined reclassification when combining hydrocortisone with an antifungal.
4. In 2016, the Australian Delegate approved the reclassification of 1% hydrocortisone in 15 g packs on the grounds that it is more effective than 0.5% hydrocortisone and has a similar side effect profile.

The Committee noted that by reclassifying 1% hydrocortisone when combined with an antifungal in a reduced pack size of 15 g as a pharmacy-only medicine, this would harmonise with Australia. It was also noted that if they extended this classification to children aged 12 years of age or younger, they would completely harmonise with the Australian Schedule.

The Committee noted the current classification of hydrocortisone in New Zealand:

• Prescription for hydrocortisone; except when specified elsewhere in this schedule.
• Restricted for hydrocortisone and hydrocortisone acetate but no other esters of hydrocortisone; for dermal use in medicines containing 1% or less but more than 0.5% by weight of hydrocortisone base with no other active ingredient except an antifungal and in a quantity of 30 grams or less or 30 millilitres or less per container; in rectal medicines containing 1% or less but more than 0.5% by weight of hydrocortisone base and in combination with a local anaesthetic and in a quantity of 35 grams or less per container or up to 12 suppositories per pack.
• Pharmacy-only for hydrocortisone and hydrocortisone acetate but no other esters of hydrocortisone; for dermal use in medicines containing 0.5% or less by weight of hydrocortisone base with no other active ingredient except an antifungal and in a quantity of 30 grams or less or 30 millilitres or less per container; in rectal medicines containing 0.5% or less by weight of hydrocortisone base and in combination with a local anaesthetic and in a quantity of 35 grams or less per container or 12 suppositories or fewer per pack.

The Committee discussed the availability of 1% hydrocortisone in combination with an antifungal as a pharmacy-only medicine in a 15 g pack, and whether there was a need for consultation with a pharmacist for this pack size and amount.

1. Several members made the comment that a 15 g pack size of 1% hydrocortisone in combination with an antifungal limited the length of time of use.
2. It was noted that providing a reduced pack size of 15 g of 1% hydrocortisone in combination with an antifungal as a pharmacy-only medicine would not prevent a consultation, as a pharmacist would be onsite to initiate a discussion or the consumer would be able to seek advice from a pharmacist.
3. However, a number of Committee members valued the importance of a required consultation, and preferred the existing classification.
4. Concerns were raised that as a pharmacy-only medicine, 1% hydrocortisone in combination with an antifungal would promote pharmacy shopping and remove record keeping and monitoring provided by pharmacists to allow them to recommend a referral to see a general practitioner at the restricted medicine classification.
5. The Committee did not consider that amending the classification from restricted medicine to pharmacy-only medicine would significantly improve accessibility.

The Committee was primarily concerned about the lack of consultation if the classification were to change and the side effect profile of 1% hydrocortisone. The Committee expressed concern that they would not be comfortable reclassifying 1% hydrocortisone as the lone active ingredient as a pharmacy-only medicine due to the side-effect profile and therefore could not justify reclassifying hydrocortisone 1% in combination with an antifungal.

Recommendation

That hydrocortisone when combined with an antifungal should not be reclassified as a pharmacy-only medicine.

c. Levocetirizine

The ACMS recommended that a separate schedule entry in the Poisons Standard for levocetirizine be included in Schedule 2 (pharmacy-only medicine), and that levocetirizine should be scheduled the same as cetirizine.

The Committee considered harmonising with the above classification.

The Committee noted that the levocetirizine was already captured under the wording of cetirizine, but that classification of levocetirizine would make it clearer for the pharmaceutical industry and healthcare professionals.

Recommendation

That levocetirizine should be classified as a pharmacy-only medicine.

d. Naloxone

The ACMS recommended a new restricted (Schedule 3) medicine entry for naloxone when packaged and labelled for the treatment of opioid overdose.

The ACMS had based its recommendations on the following:

• naloxone is a well-tolerated, life-saving medicine with minimal side effects that naloxone is used as an antidote to opioid overdose
• the benefits of increasing availability of naloxone outweigh the risks.

However, the ACMS commented that:

• the dose form, labelling and packaging of Schedule 3 naloxone must be made suitable for consumer use
• naloxone should not replace other resuscitation treatments and procedures.

The Committee considered harmonising with the above classification.

The Committee considered the following points:

1. patient access would improve with the reclassification of naloxone for the treatment of opioid overdose, and the effectiveness of the reclassification would be dependent on incorporation of other initiatives such as guidance on its provision by pharmacists
2. naloxone is highly efficacious as it reverses symptoms within a few minutes, and is a life-saving intervention
3. the duration of the effects of naloxone last between one to four hours, and is dependent on dose, frequency of dose and what drugs were used that caused the overdose
4. there are an increasing number of countries with classifications of naloxone that are very similar to the proposal of a restricted medicine. This includes some jurisdictions of the United States, Ireland, Canada, Australia and Scotland
5. the therapeutic index of naloxone is acceptable, as naloxone can be given at high doses without significant adverse or toxicological effects
6. there could be concern if naloxone was used to treat someone that had overdosed on a substance other than an opioid or if naloxone was administered by someone other than a health professional. However, with the latter, the risk of administration of naloxone by a peer was low and outweighed delaying treatment
7. there would be a need for a mechanism to incorporate intervention counselling
8. the risks of improving access to naloxone are outweighed by the lifesaving intervention
9. there is minimal risk of abuse of naloxone.

The Committee noted the following discussion points:

10. opioid prescriptions are increasing worldwide and in New Zealand
11. whether access should be limited to pharmacists or should be wider and include other professions such as paramedics, general practitioners, peers and volunteers
12. countries that have the equivalent of the proposed naloxone reclassification have a wide range of administration and training programmes that range from workshops to videos, and that some included a syringe exchange programme
13. peer administration is globally acceptable
14. naloxone is also indicated for babies with respiratory depression, and the Committee did not wish for the classification change to capture this indication
15. the Committee noted that there are two approved products available; a glass ampoule and a prefilled syringe. The Committee considered that a prefilled syringe would be easier to use, and that a glass ampoule would require a syringe and needle kit to be used by the person administering the dose. The Committee understood the convenience of the prefilled syringe but noted that this may result in reduced access, and therefore considered that both presentations should be reclassified. The Committee also noted that the ampoules are only available in a 5-pack and did not want to create barriers to access by requiring a manufacturer's original pack.

The Committee concluded that the benefits of the reclassification outweighed the risks as lives could be saved by increasing access. The Committee considered that the reclassification should require that naloxone be supplied in an emergency pack that includes advice on what to do in an overdose situation. The Committee noted that the advice should emphasise the importance of calling for ambulance support as naloxone is a relatively short-acting medicine, meaning opioid overdose could return following a single dose, and putting the patient in recovery position

Recommendation

That naloxone should be reclassified as a prescription medicine except when provided as part of an emergency kit which includes information on how to identify opioid overdose, how to draw up and administer an intramuscular injection, and advice on other steps to take to mitigate risk such as putting the patient in the recovery position, and calling an ambulance for further medical support with the finer details to be determined by the appropriate organisation.

e. Lisdexamphetamine

In March 2013, the ACMS recommended that lisdexamphetamine be listed as a controlled drug (Schedule 8).

The Chair noted that the Misuse of Drugs Act 1975 would be the best legislative framework to regulate the use of lisdexamphetamine, and recommended that lisdexamphetamine be referred to the Expert Advisory Committee on Drugs (EACD).

The Secretariat confirmed that lisdexamphetamine had been referred to the EACD.

9

Agenda items for the next meeting

The following items will be added to the agenda of the next meeting:

1. review of the outcomes from the Australian Committee on Medicine Scheduling:
   • reclassification of codeine
   • reclassification of tramadol
2. review of OTC paracetamol pack sizes
3. the criteria the MCC considers when assessing a medicine classification.

10

General business

10.1

Calcium hydroxylapatite and polycaprolactone as dermal fillers

The Committee was made aware that calcium hydroxylapatite and polycaprolactone were classified as prescription medicines by the ACMS in 2014.

The Committee was informed that as dermal fillers, such as calcium hydroxylapatite and polycaprolactone, are captured as medical devices in New Zealand, they are not regulated by the Medicines Act 1981 and that the Committee will not be considering to harmonise with the Australian Schedule.

The Committee was concerned that dermal fillers as medical devices could be administered by beauty therapists that are not necessarily a qualified health professional. The Chair explained that when the aforementioned products are used in this way, they would be regulated under the Health and Disability Commissioner Act 1994 rather than the Medicines Act 1981.

The Committee recommended that Medsafe should consult on changing the category of dermal fillers back to a medicine.

11

Date of next meeting

This year the Medicines Classification Committee will be meeting three times to accommodate an extraordinary meeting.

An extraordinary meeting will be held on Tuesday 19 July only for medicines also contained in natural health products.

The next general meeting will be held in October 2016.