1

Welcome

Prior to formally opening the meeting, the Chair acknowledged the recent efforts of all New Zealanders to eliminate COVID-19 from the country. The Committee was shown the WHO video Sharing COVID-19 Experiences: The NZ Response (https://www.youtube.com/watch?v=bLT-XdPRUAA)

The Chair opened the 64^th meeting at 9:40 am with a karakia and welcomed Dr Marcia Walker as the New Zealand Medical Association nominated member on the Committee and guests.

The Chair thanked the Committee members for attending the meeting and for playing an important role during the COVID-19 pandemic and lockdown period. It was acknowledged that many people had to step away from their usual roles and routines to ensure the health and safety of New Zealanders, including those present.

2

Apologies

Kerri Meidema (comments on agenda items received by the Chair)

3

Confirmation of the minutes of the 63rd meeting held on 10 October 2019

The minutes of the 63^rd meeting were accepted as a true and accurate record. The minutes were signed and dated by the Chair.

4

Declaration of conflicts of interest

Conflict of Interest forms were returned to the Secretary. The Chair concluded that there were no interests which would pose a conflict with any of the items on the agenda.

5

Matters arising

5.1

Objections to recommendations made at the 63rd meeting

No valid objections were received.

5.2

Gazette notice to implement recommendations made at the 63rd meeting

It was noted that three separate Gazette Notices were published subsequent to the 63^rd meeting, due to various activities post-meeting. One New Chemical Entity was gazetted as prescription in December 2019 shortly before the end of the objection period as the product approval was about to be gazetted. Other recommendations were held for the full objection period. All recommendations were gazetted in March 2020 after the Delegate endorsed the recommendations except for Artemisia annua extract as a review of the recommendation was still being undertaken. Artemisia annua extract was gazetted in May 2020.

5.3

Update on outstanding agenda items from the 63rd meeting

(9)(a) Opportunities to optimise access to vaccines (as discussed in agenda item 6.1 of the 63^rd meeting)

(9)(b) alkyl nitrites (as discussed in agenda item 8.2.1.a of the 63^rd meeting)

(9)(c) an information paper to update the Committee on CBD products and the medicinal cannabis scheme

5.3 (a) The Immunisation Team, Ministry of Health provided a written update that widening access to immunisation services is a key part of the Ministry’s immunisation strategy. Vaccine reclassifications have been undertaken on a handful of vaccines and is used by the sector to increase access (primarily through pharmacies). Classification is an important part in widening this access, but is only part of the vaccination landscape. Vaccination has many system controls around the Pharmaceutical Schedule, supply chain and contracting that can be used to leverage improved access. The Ministry would like to move towards a consistent, robust and accessible system, where the system decides the eligibility criteria not the classification. The aim is to improve access, improve flexibility, improve coverage and stop fragmentation of record keeping and services. PHARMAC and the Ministry have commenced work on this but progress has been impacted by the COVID-19 response.

The Committee agreed that an improved system was the goal, and it was important to look at the safety of the vaccination in the context of the team delivering it, rather than just through a reclassification lens. It was considered that the Committee could act as a safety net if the system required reclassification.

The Committee commented that the current system had different system controls for different types of vaccinators (e.g. pharmacist vaccinators vs authorised vaccinators) and this produced system barriers and inefficiencies. Additionally, there were also communication, IT system and funding issues. The Committee agreed that a wider system change would be more sensible than a piecemeal vaccine-by-vaccine approach.

The Committee wished to note that they strongly support the initiatives by the Immunisation Team, and it was agreed that the Chair would write formally to the Immunisation Team, including the submissions on vaccination from the 64^th agenda, many of which commented on these wider system issues. It was also agreed to invite the Immunisation Team and Primary Care Team of the Ministry of Health to meet with the Committee to discuss how classification can help achieve the goals of wider access to immunisations within a clearer, more person-centric system, either at the next meeting or in an extraordinary meeting as needed to support this work.

5.3 (b) At the 63^rd meeting under the harmonisation with Australia agenda item, it was noted that Australia had scheduled isopropyl nitrite and n-propyl nitrite, as Schedule 10 substances, had introduced a class entry for alkyl nitrites (poppers) at Schedule 4 (prescription), and down scheduled amyl nitrite to Schedule 2 (pharmacy medicine).

The Committee noted that there was no class entry for alkyl nitrites in New Zealand, even though most were classified as prescription medicines. In NZ, isopropyl nitrite and n-propyl nitrite were unscheduled and therefore freely available. The Committee recommended that there be a class entry for alkyl nitrites, which brought isopropyl nitrite and n-propyl nitrite into alignment with the other alkyl nitrites. However, no decision was made on down scheduling of any individual alkyl nitrite as the Committee felt it did not have enough information. The Committee requested more information.

Feedback received from the Rainbow Community, Men who have Sex with Men (MSM) and other supporting organisations provided more information on the use of poppers and indicated that there was confusion over the practical effects of the recommendation and did not take into account alternative classification proposals for the recommendation.

The Committee felt that the decision to propose a class alkyl nitrite entry was the only recommendation available, as adverse reactions and interactions of isopropyl nitrite and n-propyl nitrite were more serious than the other alkyl nitrites and due to the fact that the majority of these substances have been classified as prescription medicines for many years.

At the 63^rd meeting and the Committee had asked for further information. Contact with the Therapeutic Goods Administration had indicated that while there is no approved amyl nitrite product available for over-the-counter sale, there has been some interest in submitting an application for approval although this has not occurred yet.

The Committee asked, in response to the feedback from the sector, for information on the effect on businesses in Australia in the wake of the changes there, evidence for claims of development of a black market since their reclassification, and any other impacts or consequences.

The Chair refocussed the discussion on the documented harms from not using these products, such as anal tears. The Chair noted that she would be interested in meeting the affected community with other Ministry officials to explore any options, to understand issues of access via health professionals, and to work out the next steps. More information from the community was needed before a decision could be made.

While members agreed to this approach, there was discussion that having access without the intervention of a health professional was not desirable, as these products did have risks, especially with medicine and health condition interactions. In addition, it was unclear if sexual health clinics may be precluded from supplying these products if the classification was changed to restricted/pharmacy only medicine, but it was noted they could supply if the classification was general sale.

The committee noted that discussion on the classification was moot without an approved product in the market.

It was reiterated that alkyl nitrites are medicines and must be looked upon as such in the first instance, before looking at the access issue. Issues to explore with the sector include determining interested and trusted organisations, health clinics and health professionals. It was acknowledged that some people would not be comfortable going to their GP, but it was considered that access mainly via sex shops was unlikely to mitigate risks.

It is noted that in future, the Committee has asked for changes to the process for the Harmonisation with Australia agenda items where these are considered for discussion first, rather than recommendation the first time they are brought to the attention of the Committee. This allows the Committee to reach out to the affected communities discuss matters arising to avoid unintended consequences.

Conclusion: The Chair and Ministry officials will meet with the sector while further information on impacts in Australia is sought.

5.3 (c) Vidhiya Damodaran, Senior Advisor in the Regulatory Practice and Analysis Team, Medsafe gave an informational presentation on the medicinal cannabis scheme and on CBD regulation [attached]. The scheme is to allow the prescribing of quality medicinal cannabis products in New Zealand.

The Committee noted the scheme came into effect on 1 April 2020 and that as unapproved medicines, they do not fall under the remit of the Committee. The Chair indicated that the fact these products are unapproved is not well understood, the scheme mainly relies on informed consent, and was concerned what this means for patient harm. The Committee was advised that information for prescribers will be available on the Medicinal Cannabis website.

It was noted that suppliers of medicinal cannabis products could decide to use the Medicines Act pathways to approval rather than the medicinal cannabis scheme, especially for those products where there is evidence of an effect, such as Dravet syndrome and multiple sclerosis. It was also noted that the more clinical trials that are undertaken, the likelihood of these products going through a Medicines Act pathway may increase. This would enable these products to be advertised and potentially reclassified at a less restrictive classification.

[Presentation]

6

Submissions for reclassification

6.1

Human Papillomavirus (HPV) vaccine – proposed change to the prescription classification statement
(Pharmaceutical Society of New Zealand, the Pharmacy Guild of New Zealand and Green Cross Health)

Purpose

This is a submission (PDF, 569 KB, 35 pages) from the Pharmaceutical Society of New Zealand, the Pharmacy Guild of New Zealand and Green Cross Health. The applicants propose four options for reclassification, all for prescription medicine except when, with pharmacist vaccinator training and complying with Ministry of Health immunisation standards. The other options include either an age limit of 13 years or older, or 16 years or older, and with or without the intern pharmacist being able to administer.

The current classification of human papillomavirus is prescription.

Background

This is the first time HPV vaccine has been considered by the Committee.

Comments

Nine comments were received about this agenda item. All comments were generally supportive, with the majority preferring Option 1 (no age specified). There were a number of comments on the piecemeal approach to immunisation, which was discussed in Agenda Item 5.3(a).

Discussion

The Committee noted that the submission had an inaccuracy regarding information going into the National Immunisation Register (NIR). The current automatic process only supports the MMR and influenza vaccines, so HPV vaccinations by pharmacists would need to be uploaded into the NIR manually.

The Committee commented that the proposal had four options. Most of the submissions did not comment directly on the options as they appear to have no issues with the age or intern vaccinators, and the majority of comments were on IT issues or provision of stock. Other feedback was of a broader contextual nature on issues that do not affect the classification decision (cf. agenda item 5.3(a)).

The Committee discussed specifying age in the classification. Option 1 does not specify an age. The Committee did not want to add barriers to access, and while they could see the logic of avoiding the school-based programme, it was prudent to have another route of access in case the programme was missed. It was noted that many vaccines have age ranges and adding another range could be confusing.

Previous Committee discussions on intern pharmacists had essentially set a precedent where intern pharmacists were able to administer certain vaccines if trained, and there was no desire to move away from this approach.

It was noted that this is an expensive medicine and even if the classification was changed, lack of funding would still be a barrier to access.

It was noted that pharmacist vaccination training does not include children, especially those under 3 years. If HPV was reclassified without an age limit, this would be an anomaly for vaccinations. However, the Committee concluded that they were satisfied that no age range was needed as there are other controls via funding and the vaccine indications (for HPV vaccine this is 9 years) to capture the age.

Option 1 was supported.

Recommendation

To change the Human Papillomavirus (HPV) vaccine to Prescription Medicine, except when administered by a registered pharmacist or registered intern pharmacist who has successfully completed a vaccinator training course approved by the Ministry of Health and who is complying with the immunisation standards of the Ministry of Health.

6.2

Cetirizine – proposed change to the pack size limit
(AFT Pharmaceuticals Limited)

Purpose

This is a submission (PDF, 1443 KB, 24 pages) from AFT Pharmaceuticals proposing to increase the pack size limit of cetirizine hydrochloride for general sale from five days' supply to ten tablets.

The current classification of cetirizine is:
Prescription; except for oral use
Pharmacy Only; for oral use except in divided solid dosage forms for oral use containing 10 milligrams or less of cetirizine hydrochloride 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
General Sale in divided solid dosage forms for oral use containing 10 milligrams or less of cetirizine hydrochloride 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

There are currently 9 medicines approved in New Zealand containing the active ingredient cetirizine hydrochloride in packs of five 10 mg tablets.

Background

At the 8^th meeting on 6 December 1991, the Committee recommended that cetirizine be classified as a prescription medicine. At the 9^th meeting on 28 May 1992, the recommendation was for cetirizine to be classified as pharmacy-only. At the 16^th meeting on 24 April 1994, the Committee had requested that the Medicines Adverse Reactions Committee should actively seek further information about cetirizine and loratadine. However, when considering this data at the 17^th meeting on 15 May 1997, it was agreed that no further data had been produced which would cause them to reconsider the present classification of either cetirizine or loratadine and it was concluded that no further action was necessary at that point.

At the 46^th meeting, the Committee concluded that both cetirizine hydrochloride and loratadine should be reclassified from pharmacy-only medicine to general sale medicine when in packs containing sufficient tablets for only five days' supply and when used for Seasonal Allergic Rhinitis.

Comments

One comment was received about this agenda item. The submission did not support the change in pack size.

Discussion

Cetirizine is a second-generation antihistamine and has a good safety profile. The Committee discussed the reasons for an increase in General Sale pack size from 5 tablets to 10 tablets (the equivalent of 5 days to 10 days usage). It was noted that cetirizine has a contraindication for people with a glomerular filtration rate (GFR) > 30mL/min and that many people are unaware of their renal function status. The dosage of 5 mg daily of cetirizine is likely safe for people with impaired renal function for 5 days, but as it significantly affects the half-life, a 10-day regimen may not be safe.

It was considered that a 5-day self-selected supply is sufficient for a person to observe if it has any effect on the symptoms of seasonal rhinitis. If there was no effect, medical advice could be sought that is timely and appropriate.

The Committee compared the General Sale supply of loratadine and fexofenadine. Loratadine has a 10-day supply, while fexofenadine has a 5-day supply. It was noted that cetirizine has a better efficacy profile than loratadine but has a higher likelihood of cognitive impairment (drowsiness). There is a difference in effects between cetirizine and loratadine with regard to renal impairment, where loratadine has an insignificant effect on half-life in people with renal impairment.

The Committee concluded that there were no clear benefits for providing a 10-day supply of cetirizine hydrochloride, but there were risks.

Recommendation

That the pack size should remain at 5 tablets for General Sale packs.

6.3

Pholcodine – reclassification from a pharmacy medicine to a restricted medicine (Medsafe)

Purpose

This is a submission (PDF, 1051 KB, 62 pages) from Medsafe proposing to change the classification of pholcodine from a pharmacy medicine to a restricted medicine.

The current classification of pholcodine is:
Prescription; except when specified elsewhere in this schedule
Pharmacy only; in medicines for oral use containing not more than 15 milligrams of pholcodine per solid dosage unit or per dose of liquid with a maximum daily dose not exceeding 100 milligrams of pholcodine, when combined with 1 or more active ingredients in such a way that the substance cannot be recovered by readily applicable means, or in a yield that would constitute a risk to health, when sold in a pack approved by the Minister or the Director-General for distribution as a pharmacy-only medicine

There are currently 16 medicines that are approved in New Zealand containing the active ingredient pholcodine.

Background

At the 55th meeting, the Committee considered a submission to change the classification wording for numerous substances, including pholcodine. The submission proposed to remove references to approved or manufacturer's original packs. The Committee deferred a decision due to insufficient information.

At the 61^st meeting, The Committee agreed that pholcodine has limited potential for abuse. A rare but fatal association with anaphylaxis and neuromuscular blockers and pholcodine was discussed but the evidence for this was considered limited. The Committee discussed how OTC medicines sometimes are not perceived by patients as medicines and therefore it is more difficult to identify this when taking a patient's medication history. However, the Committee concluded that there were minimal safety concerns around pholcodine and that the current classification is appropriate.

The Committee agreed that consumers can appropriately self-manage coughs and cold. There are alternative cough and cold products available OTC.

The Committee suggested that Medsafe should review the risk-benefit profile and efficacy of pholcodine, which is a grandfathered medicine.

Medsafe’s review was referred to the Medicines Adverse Reactions Committee (MARC) at their December 2019 meeting. The MARC looked at the association between pholcodine and neuromuscular blocking agent anaphylaxis and found while efficacy studies were inferior, adverse reactions were rare but serious and there must be a pre-sensitisation. People can be sensitised from a number of sources, e.g. cosmetics and chemicals used in occupations such as hairdressing. Studies have noted that the Immunoglobulin E (IgE) response for pholcodine go down when pholcodine is not in the market, so studies have narrowed this down to medicinal pholcodine as a major sensitizer. However, the evidence is insufficient. The MARC and Medsafe submission recommend a change in classification to restricted (pharmacist only) to ensure an interaction with a pharmacist.

Comments

Eight comments were received about this agenda item. Seven comments opposed the proposal, preferring no change. The College of Anaesthetists support the proposed change to restricted medicine but would also support a prescription classification.

Discussion

The Committee was interested in what effects the absence of pholcodine had had in countries where it has been removed from the market, such as Sweden. Sweden had an alternative product for dry coughs but New Zealand has few medicinal alternatives. The current amount of pholcodine purchased OTC in New Zealand is unknown as this may have changed due to the recent classification changes for other cough suppressants, such as dextromethorphan, but is unlikely to be high volumes.

The Committee discussed that the efficacy data was weak and old, but it was unlikely that better data would be obtained as it is an old product, countries are moving away from using pholcodine, and there is no reason to repeat efficacy studies so the efficacy evidenceis unlikely to change. However, this does not mean there is no need for the product as there is still consumer demand.

It was noted that anaphylaxis is rare and neuromuscular blocking agent anaphylaxis is rarer again. A person would have to have repeated exposure to be at risk and that exposure can come from a number of substances in the environment. The causality is unclear.

There is evidence of harm and it is noted there is some concern about masking a cough. It is likely that if the classification is restricted medicine then pharmacists would limit the supply to those who don’t need it and can add value by way of clinical intervention.

The change in classification may not mitigate the risk of anaphylaxis under anaesthetic, as the sensitisation may occur from exposure to a number of substances, but the interaction with the pharmacist may reduce the risk to the individual person.

It was noted that most submitters opposed the reclassification but the chance to reduce the volume used by intervention of a pharmacist may be useful. The Committee discussed reasons to retain the current classification, such as there are no other alternatives, that the connection with neuromuscular blocking agents is not clear due to other environmental factors, and mitigations such as taking a complete history pre-surgery. However, it was considered that these are not compelling reasons to retain the current classification and the risk can be best managed by moving to a restricted medicine classification where people who need it can access it from a pharmacist.

Recommendation

To change the classification of pholcodine from pharmacy to restricted (pharmacist only).

7.

New medicines for classification

7.1

New chemical entities

7.1a

Galcanezumab

Galcanezumab is a humanized Immunoglobulin G4 monoclonal antibody specifically binding to calcitonin gene-related peptide (CGRP) without blocking the CGRP receptor. The binding to CGRP inhibits its activity as a sensory neuropeptide in the trigeminal system and the CGRP signalling pathway, a fundamental mechanism in the pathophysiology of migraine.

Recommendation

That galcanezumab should be classified as a prescription medicine.

7.1b

Plitidepsin

RecommendationThat plitidepsin should be classified as a prescription medicine.

[Secretary’s Note: This substance appears to have been classified at the 63^rd meeting]

7.1c

Baloxavir marboxil

Baloxavir marboxil is a virus replication (polymerase acidic endonuclease) inhibitor and is indicated for the treatment and prohylaxis of influenza.

Recommendation

That baloxavir marboxil should be classified as a prescription medicine.

7.2

New chemical entities identified by Medsafe

7.2a

Cilnidipine

Cilnidipine is a novel calcium antagonist and is a dual blocker of L-type and N-type calcium channels. It is used as an antihypertensive. It was developed in Japan and appears to have similar blood pressure lowering efficacy as amlodipine, but it does not cause amlodipine’s reflex tachycardia. Cilnidipine is not approved in Australia, the United Kingdom or with the Food and Drug administration (FDA).

Recommendation

That cilnidipine should be classified as a prescription medicine.

8

Harmonisation of the New Zealand and Australian schedules

8.1

New chemical entities which are not yet classified in New Zealand

8.1.1

From 1 October 2019, lorlatinib is classified as a prescription medicine in Australia.

Potential impact on products in the New Zealand market:
There are no products currently approved or pending containing any of the specified substances.

Recommendation

That lorlatinib should be added to the New Zealand Schedule as a prescription medicine.

8.1.2

Niraparib

Niraparib is an oral, highly selective Poly(ADP-Ribose) Polymerase 1(PARP1) and Poly(ADP-Ribose) Polymerase 2 (PARP2 )inhibitor indicated for: treatment of ovarian cancer.

From 1 October 2019, niraparib is classified as a prescription medicine in Australia.

Potential impact on products in the New Zealand market:
There are no products currently approved or pending containing this substance.

Recommendation

That niraparib should be added to the New Zealand Schedule as a prescription medicine.

8.1.3

Darolutamide

Darolutamide is a non-steroidal androgen receptor antagonist and is indicated for: prostate cancer, nonmetastaticand castration resistant.

From 1 October 2019, darolutamide is classified as a prescription medicine in Australia.

Potential impact on products in the New Zealand market:
There are no products currently approved or pending containing this substance.

The Committee considered the Scheduling delegate’s final decisions published on the Therapeutic Goods Administration website.

Recommendation

That darolutamide should be added to the New Zealand Schedule as a prescription medicine.

8.1.4

Alpelisib

Alpelisib is a phosphatidylinositol-3-kinase (P3K) inhibitor indicated for: breast cancer, advanced or metastatic, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)negative disease, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA)-mutated, in combination with fulvestrant in postmenopausal women, and men following progression on or after endocrine therapy

From 1 October 2019, alpelisib is classified as a prescription medicine in Australia

Potential impact on products in the New Zealand market:
There is one product pending approval containing this substance.

The Committee considered the Scheduling delegate’s final decisions published on the Therapeutic Goods Administration website.

Recommendation

That alpelisib should be added to the New Zealand Schedule as a prescription medicine.

8.2

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

8.2.1

Decisions by the Delegate – November 2019

8.2.1.a

Talazoparib is a poly ADP ribose polymerase (PARP) inhibitor indicated for: metastatic breast cancer, or locally advanced, HER2-negative, germline BRCA-mutated disease

From 1 December 2019, talazoparib is classified as a prescription medicine in Australia

Potential impact on products in the New Zealand market:
There are no products currently approved or pending containing this substance

Recommendation

That talazoparib should be added to the New Zealand Schedule as a prescription medicine.

9

Agenda items for the next meeting

10

General business

10.1

Codeine implementation

Following on from the recommendations of the 59^th meeting and the 63^rd meeting, the implementation of the change to the classification of codeine-containing products is likely to be 5 November 2020. From this date, all codeine only and codeine-containing products will only be able to be supplied pursuant to a prescription. Medsafe has worked with the pharmaceutical industry sector to identify a date for this change that is practicable. All labelling should be transitioned by May 2021. Advice to healthcare professionals on managing the clinical aspects of change will be provided by bpac^nz.

10.2

Artemisia annua extract update

The gazetting of Artemisia annua extract has generated feedback from the natural health products sector. There is disagreement that the safety issues are widespread, and that they relate only to the specific extraction method used for the Arthrem and Go Healthy® products that had serious adverse reaction reports.

Medsafe met with representatives of the natural health product sector and they will provide a submission to the Committee outlining this evidence and proposing an alternative classification.

10.3

Acknowledgment to Medsafe

A letter was received from the MARC expressing support for the recent reclassification of dextromethorphan.

The Chair also acknowledged the efforts of Medsafe during the COVID-19 lockdown to maintain the supplies of medicines in New Zealand during this challenging time, and thanked Medsafe for the work done.

11

Date of next meeting

A date in October 2020 will be confirmed.