Committees

Published: 17 January 2018

Minutes of the 59th meeting of the Medicines Classification Committee held in Wellington on Tuesday 7 November 2017 at 9:30 am

Present:
Dr S Jessamine (Chair)
Dr D Burrell
Mrs A Harwood
Mrs K Miedema
Mrs A Shirtcliffe (Deputy Chair)
Professor L Toop
Ms A Kerridge (Secretary)

In attendance (from Medsafe):
Dr J Barber (Advisor Science, Product Regulation)
Mr L Holding (Team Leader, Committee and Support Services)
Dr S Kenyon (Manager, Clinical Risk Management)
Ms C Low (Advisor, Regulatory Practice and Analysis)
Ms V Mills (Advisor, Regulatory Practice and Analysis)

In attendance (from the Ministry of Health):

Mrs S Swan (Chief Advisor, Strategy and Policy)

1

Welcome

The Chair opened the 59th meeting at 9:30 am and welcomed members and guests.

2

Apologies

No apologies were received.

3

Confirmation of the minutes of the 58th meeting held on 16 May 2017

The minutes of the 58th meeting were accepted as a true and accurate record. The 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 Miedema declared that her fellow director of Olsen's Pharmacy (2002) Limited had submitted a comment regarding agenda item 5.3 - codeine. The Committee agreed that this declaration should not prevent Mrs Miedema from fully participating in the discussion or from contributing to the recommendation.
  2. Professor Toop declared a close relationship with the Royal New Zealand College of General Practitioners in that most recommendations impact general practitioners as prescribers in one way or another. The Committee agreed that this ongoing declaration should not prevent Professor Toop from fully participating in the discussion or from contributing to any recommendation.

5

Matters arising

5.1

Objections to recommendations made at the 58th meeting

No valid objections had been received.

5.2

Update on outstanding agenda items from the 58th meeting

(5.1-6.4) Selected oral contraceptives (desogestrel, ethinylestradiol, levonorgestrel and norethisterone)
(Green Cross Health Ltd and Natalie Gauld Ltd)


Medsafe wrote to Green Cross Health Ltd and Natalie Gauld Ltd requesting a timeline of milestones (eg, requested changes made to the training and monitoring procedures, selected oral contraceptives available in pharmacies, market sales data collected) that the Committee could expected to be updated on and when.

An email response was received on 6 July 2017. Although training is now available to pharmacists, the date of when selected oral contraceptives will be available in pharmacies is still unknown.

(5.1-8.2.1.b) Paracetamol


The Deputy Chair wrote back to Retail New Zealand with the list of criteria that the Committee considers when reviewing a medicine for reclassification for non-prescription sale and a comment that the sector’s approach to the sale of paracetamol will be taken into account when considering the reclassification of future medicines and their availability for general sale.

A response was received on 27 July 2017. Retail New Zealand emphasised that in the previous letter they had clearly outlined a mix of views amongst members and that some members were willing to comply with the Committee’s requests regarding paracetamol.

The Deputy Chair passed on the comments, regarding the sale of paracetamol medicines at general sale, from the Committee and Retail New Zealand to the team currently drafting the new therapeutic products regulatory regime in an email dated 27 July 2017.

(5.4) Updated version of the document titled ‘How to change the legal classification of a medicine in New Zealand’


The Medsafe consultation regarding the draft document ‘How to change the legal classification of a medicine in New Zealand’ was published on 8 November 2017. Interested parties should respond by close of business on 15 January 2018.

The Medsafe consultation regarding observers at Ministerial Advisory Committees was also published on 8 November 2017. Interested parties should respond by close of business on 15 January 2018.

(5.5) Medicine reclassification – proposed additional process when considering the reclassification of prescription medicine to restricted medicine
(Pharmacy Council)


The proposed additional process from the Pharmacy Council has been updated, added to the document ‘How to change the legal classification of medicine in New Zealand’ and included in the Medsafe consultation.

(5.6.3) Sildenafil – proposed amendment to the prescription medicine except classification
(Individual
pharmacist submission)


The Deputy Chair wrote to the Pharmaceutical Society of New Zealand (the Society) for further information on what the sector would do to ensure that patients are fully informed if they are buying a medicine that is not in the manufacturer’s original pack. Further information following their submission (made at the 55th meeting) to change the classification statements of lansoprazole, promethazine, sumatriptan, ibuprofen, omeprazole, pantoprazole, opium, phlocodine and ranitidine was also requested.

A response was received from the Society on 29 September 2017 with a letter sent by the Society on 31 January 2017 which had not been received by the Chair.

The Society has withdrawn their submission (made at the 55th meeting) to change the classification statements of lansoprazole, promethazine, sumatriptan, ibuprofen, omeprazole, pantoprazole, opium, phlocodine and ranitidine. The Society will seek to resolve their concerns outside of the Committee process.

Medsafe will write a paper summarising all medicines in Schedule 1 of the Medicine Regulations 1984 that reference the manufacturer’s original pack and the Committee deliberations behind each reference. The Medsafe paper will be added to the agenda of the 60th meeting to allow for public consultation.

Update on outstanding agenda items from the 57th meeting

(8.1.f) Flubromazolam


The classification of flubromazolam as a prescription medicine was gazetted on 9 March 2017.

The classification of flubromazolam was considered by the Expert Advisory Committee on Drugs at a meeting on 11 April 2017. No objections were received following a consultation that took place in July 2017 regarding the proposed scheduling of flubromazolam as a Class C1 controlled drug. A final decision is currently with the Minister of Health.

56th meeting


The 56th meeting for Natural Health Products, which was scheduled for late September 2016, has been postponed. As at November 2017, the Natural Products Bill is no longer on the legislative programme. The Ministry of Health is awaiting further information from the Government on the next steps for natural health products.

Update on outstanding agenda items from the 55th meeting

(8.2.1.a) Esomeprazole


The classification of 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 was gazetted as a pharmacy-only medicine on 18 August 2016.

The Label Statements Database was updated on 3 July 2017 with the following statements for esomeprazole:

  • 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.

(10.1) Calcium hydroxylapatite and polycaprolactone as dermal fillers


The Medsafe consultation on changing the category of dermal fillers back to a medicine has not yet taken place.

Medsafe is currently taking advice regarding the categorisation of dermal fillers.

Changes to the definition of medicines and medical devices came into effect on 1 July 2014. This resulted in dermal fillers (eg, collagen injections) with / without local anaesthetic included in the formulation being categorised as medical devices because of their mode if action. How this change affects those dermal filler substances that remain listed in Schedule 1 is a matter for consideration.

5.3

Codeine – proposed reclassification from pharmacy-only and restricted medicines to a more restricted classification

Purpose

To consider harmonising with Australia and reclassify all medicines containing codeine to prescription medicines.

Background

From 1 February 2018, medicines containing codeine will no longer be available without a prescription in Australia. The change to codeine access in Australia was decided by the Delegate in December 2016.

At the 57th meeting on 1 November 2016, the Committee requested that Medsafe review the outcome of the Australian reclassification to prescription medicine and provide advice on the role of codeine.

At the 58th meeting on 16 May 2017, following consideration of the requested submission from Medsafe, the Committee recommended that the sector would need to answer the following questions to allow codeine to continue to be available without prescription:

  1. what education and continuing professional development would be provided to health professionals regarding the sale and prescription of codeine to minimise the risk of misuse and addiction in consumers?
  2. how will the sector fill the data gap with respect to over-the-counter codeine use?
  3. how will the sector track the sale of codeine in pharmacy in order to better identify consumers with additional needs for pain management and / or addiction problems?
Comments

Twelve pre-meeting comments were received during the consultation period after publication of the agenda.

One supported the reclassification of codeine to prescription but wanted their comments regarding an experience of codeine addiction to remain anonymous. This comment, which outline the experience of codeine addiction, added much value to the Committee’s discussion.

Similarly, another pre-meeting comment supported the reclassification of all codeine-containing medicines to prescription medicines. The comment outlined that further education and professional development would have a limited effect in mitigating the risks of abuse and misuse with at-risk consumers. There is evidence from sales data that a significant base of codeine analgesic use remains and, although local data on misuse and abuse is limited, the international experience suggests many consumers are at risk through the continued availability of codeine over-the counter. Real-time monitoring measures are reliant upon suitable identification, such as a driving licence, which can easily be forged. It may be more appropriate to introduce initiatives to further monitor prescription use of codeine.

Ten pre-meeting comments opposed a reclassification of codeine that would reduce direct access through a pharmacist and answered the questions posed by the Committee. Of the ten, six supported a reclassification to restricted medicines.

  1. What education and continuing professional development would be provided to health professionals regarding the sale and prescription of codeine to minimise the risk of misuse and addiction in consumers?
    1. Training around managing and communicating with patients with identified problematic use of codeine would be welcomed by pharmacists and the wider health sector.
    2. Pharmacists would agree to an accreditation programme to supply codeine.
    3. A public information campaign promoting the safe use of codeine would be appreciated by pharmacists. This would create a level of public awareness for consumers around the risk of codeine misuse and addition, promote appropriate use of codeine and empower consumers with a pain management problem or codeine dependence to seek help.
    4. Pharmacists are already directed by their Code of Ethics to prevent the supply of unnecessary and excessive quantities of medicines containing codeine.
    5. The joint statement by the Pharmacy Council of New Zealand and the Pharmaceutical Society of New Zealand on the sale of codeine-containing analgesics would be updated with any requirements requested by the Committee.
    6. The medical profession, pharmacists and the public should be the target of an educational programme, funded by all major stakeholders, on the better use of analgesics including codeine-containing medicines.
    7. Training should be mandated to ensure all pharmacists who supply codeine have the knowledge required to best prevent dependence and manage potential or obvious dependence.
  2. How will the sector fill the data gap with respect to over-the-counter codeine use?
    1. Currently privacy restrictions prevent the nationwide active sharing of information.
    2. The data gap will be filled when a real-time recording and monitoring system is in place.
  3. How will the sector track the sale of codeine in pharmacy in order to better identify consumers with additional needs for pain management and / or addiction problems?
    1. Implementation of a mandatory real-time monitoring system would be supported for any pharmacy wanting to supply medicines containing codeine over-the-counter.
    2. The Pharmacy Council of New Zealand is willing to actively distribute information to ensure pharmacists are informed of and able to contribute to medication safety campaigns, including monitoring the purchase of non-prescription codeine-containing medicines and informing the public of risks associated with misuse and overuse of such products.
    3. The Pharmacy Guild of New Zealand is currently working with other sector organisations to implement a real-time recording and monitoring system.
    4. To be successful any real-time monitoring system must be mandated.
    5. A real-time monitoring system should also monitor the sales of Gees linctus and could include other misused over-the-counter medicines such as cyclizine.

A two-year suspension in any reclassification of medicines containing codeine has been requested to allow time to implement a real-time monitoring system and pharmacist training programme.

One comment was received after the deadline for comments in agenda items and did not support a more restrictive classification because of the inconvenience and costs associated with visiting a general practitioner.

The Committee raised concerns that none of the submissions from individual pharmacists referred to the joint statement from the Pharmaceutical Society of New Zealand and the Pharmacy Council of New Zealand regarding the sale of codeine-containing analgesics. The joint statement includes ‘Recording details of the sale [of codeine] in an electronic database, such as your dispensary system, provides additional information regarding patient medication use particularly in areas where a shared patient record is accessible. Any concerns about frequent purchasers should be reported to Medicines Control.’

The Committee were disappointed that comments had not been received from any of the medical organisations or general practitioners. The Committee members nominated by the New Zealand Medical Association explained this was because they didn’t feel the questions asked at the last meeting were aimed at them, even though the first question was aimed at all health professionals. It was noted that most had commented on the Medsafe submission at the last meeting.

Additional information considered


The Committee also considered the following documentation:

  1. AIHW. 2016. National Drug Strategy Household Survey 2016: Detailed Findings. Canberra: Australian Institute of Health and Welfare.

    The Survey showed that three in four recent painkiller misusers had misused an over-the-counter codeine medicine in the last 12 months. Codeine is the most abused over-the-counter analgesic and the second most abused prescription analgesic. It was noted that an increase in analgesic misuse (prescription and over-the-counter) was not indicated in the trends. Overall, illicit use of drugs has remained stable between 2013 and 2016.

  2. Boudreau M. 2017. Controlled Drugs and Substances Act – Notice to interested parties – Non-prescription availability of low dose codeine products. Canada Gazette 151 (36). URL: www.gazette.gc.ca/rp-pr/p1/2017/2017-09-09/html/notice-avis-eng.php#ne3 (accessed 20 October 2017).

    Potential changes to New Zealand and Canada’s regulations to require all medicines containing codeine to be sold by prescription would be in line with those already in place in many countries, including Australia, Belgium, Croatia, Czech Republic, Finland, France, Greece, Iceland, India, Italy, Norway, Russia and Sweden.

  3. Codeine move would punish consumers, won’t stop misuse – Coney. Stuff, 15 August 2017.
  4. MacKinnon J. 2017. Correspondence: Reclassifying codeine to prescription-only. The Pharmaceutical Journal 299 (7904) 101.
  5. Pharmacists lobby against codeine prescription move. Radio New Zealand, 18 October 2017.
  6. Robb G, Loe E, Maharaj A, et al. 2017. Medication-related patient harm in New Zealand hospitals. New Zealand Medical Journal 130 (1460) 21-32.
  7. Serious pain coming as NZ’s prescription opioid use soars. Stuff, 9 July 2017.
  8.  Waitemata DHB votes to take codeine off pharmacy shelves. Stuff, 9 August 2017.
  9. WDHB CADS. 2017. Prescription and over-the-counter drug misuse: A focus on codeine. Submission to the Medicines Classification Committee. Auckland: Waitemata District Health Board Community Alcohol and Drug Services.

    The WDHB CADS submission stated an increased incidence of over-the-counter dependence on codeine but there are no specific figures to back up the claim (ie, data provided is over a one year period so it is difficult to see a trend). The submission also states the misuse of prescription and over-the-counter medicines containing codeine is increasing. The key problem in over-the-counter medicines containing codeine appears to be taking more than the recommended dose.

One Committee member gave a brief report on the evidence regarding the use of codeine, for acute pain post-intervention, presented in the Cochrane Database. Evidence suggests a single dose of 60 mg codeine can give pain relief for 4-6 hours in 50% of patients. Adverse events are greater in codeine compared to placebo but the difference is not statistically significant. Paracetamol combined with 60 mg codeine is clinically useful in relieving pain in 50% of patients with moderate to severe post-operative pain. Codeine at doses of 30 mg to 120 mg alone or in combination with paracetamol provides a good level of pain relief for some people with cancer pain. Codeine at a dose of 60 mg combined with 400 mg ibuprofen demonstrates good efficacy for pain relief. Codeine at a dose of 60 mg is prescribed and not available over-the-counter. The data suggests the combination of ibuprofen and codeine is better than either medicine alone. A similar number of patients experience adverse effects with placebo. This evidence suggests an argument could be made for a medicine containing codeine to continue to be available in a pharmacy for acute pain.

Discussion – Education and professional development

One member commented that in New Zealand general practitioners do not effectively manage pain as well as they could, mainly due to a lack of education. Acute and chronic pain are managed completely differently. Codeine is typically given to manage acute pain. Chronic pain management is 20% pharmacology and psychosocial factors account for the rest. Most opioids on the black market are prescribed, so switching all medicines containing codeine to prescription alone would not solve the availability issue.

Members discussed what an education campaign and professional development could involve. The following could be aimed at all healthcare professionals:

  1. small group education and discussion meetings
  2. lectures
  3. information on a website, similar to what has been done in Australia.

The Committee decided that Medsafe should write to the professional bodies (ie, New Zealand Medical Association, Royal New Zealand College of General Practitioners, Pharmaceutical Society of New Zealand, Pharmacy Council of New Zealand, Pharmacy Guild of New Zealand, New Zealand Nurses Organisation, Chairs of the District Health Boards, Dental Council and the New Zealand Dental Association) regarding the importance of better education and professional development for health professionals regarding acute and chronic pain management.

The letter should include a reminder of analgesics with the potential for abuse and of section 24(1) of the Misuse of Drugs Act 1975, that every medical practitioner commits an offence who prescribes, administers or supplies a controlled drug (which codeine is also classified) for or to a person who the practitioner has reason to believe is dependent on that or any other controlled drug. Section 24(1A) extends this offence to midwives, nurse practitioners, optometrists and designated prescribers.

Education campaigns and professional development could be targeted regionally as well as nationally.

Discussion – Monitoring the sale of codeine

A number of different systems for monitoring the sale of codeine were discussed.

MedsASSIST, a real-time recording and monitoring system for medicines containing codeine, would achieve some monitoring. TestSafe gives registered healthcare professionals access to records on prescribed medications dispensed by community pharmacies. HealthOne has a matrix of who can see what information. Many pharmacists record the sale of codeine using dispensary software which has a notes function.

The main issue with monitoring is that all pharmacists and general practitioners would need to use the same system. The key to efficient monitoring would be to ensure all systems work together so that the information does not become fragmented. Monitoring should be in real-time and there should be no opt out function.

The Committee agreed that monitoring the sale of codeine was essential no matter what the classification. When opioids are prescribed the dispensing can be tracked. Medicines Control in the Ministry of Health receive an automatic feed of dispensing records. However, this feed is not available if codeine is sold from a pharmacy without a prescription.

The Committee recommended that they should advocate the national monitoring of all medicines containing codeine which would include restricted and prescription, subsidised and unsubsidised medicines. Medsafe and the Ministry of Health should explore how the Committee could advocate a monitoring system which would build on existing systems. Any system should take into account the move in New Zealand towards electronic health records for all patients, where information follows the patient enabling them to make informed decisions about their own health care. Medsafe and the Ministry of Health could lead the discussions with the sector.

The Committee considered there is public value in collecting this data set. However the biggest barrier to collecting this data set is the current privacy laws.

Discussion – Reclassification of codeine to prescription medicine

The Health Quality and Safety Commission provide maps on the use of opioids by District Health Board. They have raised significant concerns over the use of opioids, including codeine. There is evidence of toxicity and a risk of abuse associated with combination medicines.

New Zealand appears to have a belief system that codeine is necessary, which is not supported by the currently available data on efficacy. As explained in the Medsafe submission at the 58th meeting, the hepatic CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, including codeine. CYP2D6 converts codeine in to its active metabolite, morphine, which provides its analgesic effect. However, pain relief may be inadequate in individuals who carry two inactive copies of CYP2D6 (ie, poor metabolizers), because of reduced morphine levels. In contrast, individuals who carry more than two normal function copies of the CYP2D6 gene (ie, ultra-rapid metabolizers) are able to metabolize codeine to morphine more rapidly and more completely. As a result, even with normal doses of codeine, these individuals may experience the symptoms of morphine overdose, which include extreme sleepiness, confusion, and shallow breathing.

Considering the available evidence, the Committee recommended that all codeine-containing combination medicines, both analgesics and those used for cough and colds, should be reclassified to prescription medicines. The Committee acknowledged the comments made during the consultation period and suggested an implementation date of 31 January 2020.

The Committee were informed that in Australia, the Pharmacy Guild has suggested that the Australia Department of Health consider adopting the New Zealand model of ‘prescription except when’ so that pharmacists could dispense codeine medicines without a script in certain circumstances.

The Committee briefly discussed reclassifying codeine as a prescription medicine except under specific circumstances including the accreditation of pharmacists. It was noted that the joint statement regarding the sale of codeine-containing analgesics already listed the specific circumstances that the Committee would expect in a prescription except when reclassification. The Committee understood that the prescription except when classification means that the medicine under specific circumstances becomes a general sale medicine. It was agreed that the prescription except when classification would not be appropriate for a controlled drug.

Discussion – Reclassification of codeine to restricted medicine

The Committee considered the pain relief gap that would be created by making codeine-containing combination medicines prescription only. The Committee therefore suggested that it would be useful for medicines containing codeine as the only active ingredient to be available from a pharmacist for the emergency management of acute pain. Concerns were raised regarding diagnostic accuracy if a patient presented in a pharmacy. However, there was general acknowledgement that codeine has a legitimate place as a step 2 analgesic in the World Health Organisations’ three-step pain ladder for adults.

The Committee did not consider that there was a need for a cough and cold medicine containing codeine because of the evidence of toxicity and a risk of abuse associated with combination medicines.

The Committee raised concerns that there was no restriction regarding age within the current classification of codeine. Removing the availability of codeine in liquid form implies it is not suitable for use in children 12 years of age and younger. In addition, the Nurofen Plus data sheet (currently available on the Medsafe website), suggests that ibuprofen and codeine-containing combination solid dose strength products should not be used in children below the age of 12 years because of the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine.

The Committee recommended that medicines containing codeine as the only active ingredient should be reclassified from prescription to restricted medicine; for oral use in adults and children over 12 years of age in medicines containing not more than 15 mg per solid dosage unit with a maximum daily dose not exceeding 90 mg of codeine for use as an analgesic and when sold in a pack of not more 3 days’ supply. This would also have an implementation date of 31 January 2020 to coincide with the upscheduling of codeine-containing combination medicines.

Although not in real-time, dispensary software would collect data from patients when codeine is sold as a restricted medicine. In the interim, until 31 January 2020, the sale of codeine should be monitored as per the joint statement from the Pharmaceutical Society of New Zealand and the Pharmacy Council of New Zealand regarding the sale of codeine-containing analgesics.

Discussion – codeine as a controlled drug

Under the Misuse of Drugs Act 1975, codeine is classified as a:

  • Class C2 Controlled Drug; other than a preparation or mixture described in Schedule 3, Part 6
  • Class C6 Controlled Drug; (i) Compounded with one or more other pharmacologically active ingredients in such a way that the substance cannot be recovered by readily applicable means or in a yield which would constitute a risk to health; and (ii) Containing not more than 100 milligrams of the substance in each dosage unit and with a concentration of not more than 2.5 % in undivided preparations.

Drugs that pose a moderate risk of harm are classified as Class C drugs.

The Committee discussed the option of referring codeine to the Expert Advisory Committee on Drugs with the advice that it should be rescheduled from a Class C6 drug to a Class C2 drug. Controlled drugs that are also medicines are required to meet the requirements of both the Misuse of Drugs legislation and the Medicines legislation. Where there is any inconsistency between the two sets of legislation, the Misuse of Drugs legislation takes precedence over the Medicines legislation.

The Committee agreed not to recommend making the referral to the Expert Advisory Committee on Drugs. The Committee wanted to make more practical recommendations such as education and monitoring.

Conclusion

In conclusion, the Committee felt that the recommendations made were evidence-based and considered the benefits and risks of harm from using codeine as an analgesic and a cough and cold medicine.

The current classification of codeine is:

  • prescription medicine; except when specified elsewhere in this Schedule
  • restricted medicine; in medicines for oral use containing not more than 15 mg of codeine per solid dosage unit or per dose of liquid with a maximum daily dose not exceeding 100 milligrams of codeine, when combined with one 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, for use as an analgesic and when sold in a pack of not more than five days' supply, approved by the Minister or the Director-General for distribution as a restricted medicine
  • pharmacy-only medicine; in medicines for oral use, containing not more than 15 mg of codeine per solid dosage unit or per dose of liquid with a maximum daily dose not exceeding 100 milligrams of codeine, when combined with one 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, for the treatment of the symptoms of cough and cold and when sold in a pack of not more than six days' supply, approved by the Minister or the Director-General for distribution as a pharmacy-only medicine.

The recommended classification of medicines containing codeine as the only active ingredient, from 31 January 2020, is:

  • prescription medicine; except when specified elsewhere in this Schedule
  • restricted medicine; for oral use in adults and children over 12 years of age in medicines containing not more than 15 mg per solid dosage unit with a maximum daily dose not exceeding 90 mg of codeine for use as an analgesic and when sold in a pack of not more three days’ supply.
Recommendation

That Medsafe should write to the professional bodies (ie, New Zealand Medical Association, Royal New Zealand College of General Practitioners, Pharmaceutical Society of New Zealand, Pharmacy Council of New Zealand, Pharmacy Guild of New Zealand, New Zealand Nurses Organisation, Chairs of the District Health Boards, Dental Council and the New Zealand Dental Association) regarding the importance of better education and professional development for health professionals regarding acute and chronic pain management, analgesics with the potential for abuse and a reminder of section 24(1) of the Misuse of Drugs Act 1975.

That the Committee should advocate the national monitoring of all codeine-containing medicines which would include restricted and prescription, subsidised and unsubsidised medicines. Medsafe alongside the Ministry of Health should explore how the Committee could advocate a monitoring system.

That, from 31 January 2020, all codeine in combination medicines, both analgesics and those used for cough and colds, should be reclassified to prescription medicines.

That, from 31 January 2020, medicines containing codeine as the only active ingredient should be reclassified from prescription to restricted medicine; for oral use in adults and children over 12 years of age in medicines containing not more than 15 mg per solid dosage unit with a maximum daily dose not exceeding 90 mg of codeine for use as an analgesic and when sold in a pack of not more three days’ supply.

That Medsafe should liaise with the sector regarding the required labelling to be included on codeine when sold as a restricted medicine.

5.4

Principles of harmonisation

At the 58th meeting, the Committee recommended that the principles of harmonisation should be added to the agenda of this meeting.

The Committee considered a number of decisions recommended by the Australian Delegate regarding proton pump inhibitors, fexofenadine and ulipristal. At the 58th meeting the Committee commented that it was difficult to harmonise with Australia when only the minutes of their deliberations were provided.

The principles of harmonisation are available on the Medsafe website and were considered by the Committee.

Two comments were received during the consultation period after publication of the agenda.

One supported the harmonisation of labelling and packaging in terms of safety directions, warning statements and common nomenclature of drugs and poisons, but did not support the harmonisation of drugs and poisons.

The other had the following suggestions for the Committee and the meeting minutes:

  1. it would be useful to have an explanation of the significance of the classification of the new chemical entities (agenda item 8.1)
  2. for each harmonisation considered it would be useful to have a summary of the change made in Australia, a link to the webpage containing the reasons behind the change in Australia and information on the current classification in New Zealand (agenda item 8.2)
  3. it would be useful to have a table on the Medsafe website that gave an overview of the Australian classification, the New Zealand equivalent and what each means in practice
  4. it would also be helpful if a link was provided to the Medsafe website with information on the principles of harmonisation.

The Committee noted the suggestions and agreed that the discussion around harmonisation would be more appropriate when considering the role of the Committee under the new therapeutic products regulatory regime. Until that time, the Committee process for harmonisation would continue in the current format. The Committee was not aware of the processes carried out by the Australian Advisory Committee on Medicines Scheduling to incorporate harmonisation with New Zealand, but noted that patient access and communal benefit were increased by New Zealand continuing to harmonise with Australia.

Recommendation

No recommendation was required.

5.5

Matters arising for information

 

5.5.1

Classification of lisdexamfetamine and palbociclib


An out-of-session consultation took place in June 2017 regarding the classification of lisdexamfetamine and palbociclib.

The Committee recommended that lisdexamfetamine and palbociclib should be classified as prescription medicines.

These classification recommendations were gazetted on 22 June 2017.

Recommendation

No recommendation was required.

5.6

Influenza vaccine – proposed amendment of the classification statement to include registered nurses

This late agenda item was not published on the Medsafe website and therefore has not been consulted on.

Influenza vaccine is currently classified as a prescription medicine; except when administered to a person 13 years of age or over by a registered 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.

Following a request from the Director of Public Health, the Committee considered extending the current classification to include registered nurses. Currently registered nurses can only administer the influenza vaccine if a medical practitioner has either written a prescription or has a standing order in place. Alternatively, section 44A of the Medicines Regulations 1984 enables registered nurses to administer vaccines as an authorised vaccinator without the need for a prescription if this is given as part of an approved immunisation programme by a medical officer of health, for example influenza vaccination in workplace settings.

There are issues associated with the supply of the influenza vaccine for vaccinator training and clinical assessment due to the prescription only status of the vaccine when administered by a registered nurse who is an authorised vaccinator in occupational settings. This causes delays in authorisation and can have a significant impact on the delivery of the annual influenza vaccination programme, especially when large volumes are delivered in a very short period of time.

The aim of extending the current classification to include registered nurses is to increase the access and convenience of obtaining an influenza vaccination, in order to increase uptake by the general population and reduce the burden of influenza. This extension would remove the need to use of section 44A of the Medicines Regulations 1984, and will enable registered nurses with the appropriate vaccinator training to provide influenza vaccine in an agile and responsive manner. This rationale aligns with the Pharmacists Vaccinator reclassification and also reduces the administrative burden associated with section 44A on health professionals.

The Committee acknowledged that, although the proposed amendment to the classification statement of influenza vaccine had not been included in the agenda, interested parties could object to the recommendation after the minutes were published. However, ideally the amendment could come into effect before the next flu season in 2018. The amendment is technical with no real change in access other than in a small number of cases where training would occur.

Recommendation

That the current classification of influenza vaccine should be amended to include registered nurses.

6

Submissions for reclassification

6.1

Hydrocortisone – proposed reclassification from prescription medicine to restricted medicine
(Zovirax Duo, GlaxoSmithKline Consumer Healthcare New Zealand Limited)

Purpose

This was a company submission requesting the reclassification of hydrocortisone 1% w/w from prescription medicine to restricted medicine when combined with aciclovir 5% w/w in primary packs of not more than 2 g for dermal use in adults or children 12 years of age and older for the treatment of herpes labialis (cold sores).

Zovirax Duo contains a combination of aciclovir and hydrocortisone. Aciclovir is currently available as a general sale medicine for external use for the treatment of herpes labialis in medicines containing 5% or less and in tubes containing 10 g or less. In New Zealand, if a medicine has more than one active ingredient the active with the most restrictive classification determines the classification of the medicine. Therefore the classification of hydrocortisone will determine the classification of Zovirax Duo.

The Committee noted there were currently no other products marketed that contained hydrocortisone in combination with aciclovir.

Background

At the 1st meeting on 13 November 1984, the Committee recommended that the classification of hydrocortisone should include the words ‘with no other active ingredient’.

At the 7th meeting on 31 July and 1 August 1990, the Committee confirmed that hydrocortisone and hydrocortisone acetate should be classified as:

  • prescription; except when contained in dermatological medicines containing 1% or less by weight of hydrocortisone base and in a quantity of 15 g or 15 ml or less per container
  • part I pharmacy; in dermatological medicines containing 1% or less by weight of hydrocortisone base and in a quantity of not more than 15 g or 15 ml per container; in rectal medicines in a non-divided dose form containing 1% or less by weight of hydrocortisone base and in combination with a local anaesthetic and in a quantity of not more than 35 g per container.

At the 9th meeting on 28 May 1992, the Committee acknowledged that the words ‘with no other active ingredient’ recommended at the 1st meeting had been omitted when hydrocortisone was discussed at the 7th meeting. Following discussion, the Committee therefore recommended that products containing hydrocortisone in combination with antifungals which are currently available over-the-counter should retain their present status. However products in combination with any active ingredient other than an antifungal should be a prescription medicine.

At the 20th meeting on 19 November 1998, the Committee recommended that there be no increase in the volume limit for 1% hydrocortisone lotions sold as restricted medicines.

At the 24th meeting on 2 November 2000, in order to harmonise with Australia, the Committee recommended that the maximum pack size limit for the sale of dermal hydrocortisone preparations as restricted medicine or pharmacy-only medicines should be increased from 15 g or 15 ml to 30 g or 30 ml.

At the 27th meeting on 23 May 2002, the Secretary reported that Australia had responded to the Committee’s recommendation not to allow steroids more potent than 1 % hydrocortisone to be available over-the-counter. Australia did not adopt the Committee’s recommendation and allowed these products to continue to be sold as Schedule 3 (restricted) medicines. The Committee agreed to review its position in two years.

At the 28th meeting on 19 November 2002, in a discussion considering the classification of clobetasone, the Chair pointed out that the Committee had made a previous policy decision not to allow steroids more potent than 1 % hydrocortisone to be available over-the-counter.

At the 33rd meeting on 9 June 2005, the Committee recommended that the policy statement of November 2000 relating to topical steroids for over-the-counter sale should be revoked.

At the 48th meeting on 30 October 2012, the Committee recommended that hydrocortisone should not be reclassified from restricted medicine to pharmacy-only medicine when for dermal use in medicines containing 1% or less by weight of hydrocortisone base in combination with an antifungal and in a quantity of 30 g or less or 30 mL or less per container.

At the 54th meeting on 24 November 2015, the Committee deferred making a decision to harmonise with the recommendation from Australia that the Schedule 3 (restricted medicine) entry for hydrocortisone should be amended to allow for 1% or less of hydrocortisone when compounded with aciclovir 5% w/w or less in primary packs of not more than 2 g for dermal use in adults and adolescents (12 years of age and older).

At the 55th meeting on 3 May 2016, the Committee recommended not harmonising and that hydrocortisone when combined with an antifungal should not be reclassified as a pharmacy-only medicine.

Hydrocortisone, and hydrocortisone acetate but no other esters of hydrocortisone, are currently classified as:

  • prescription; except when specified elsewhere in this Schedule
  • restricted; 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 g or less or 30 mL 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 g or less per container or up to 12 suppositories per pack
  • pharmacy-only; 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 g or less or 30 mL 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 g or less per container or 12 suppositories or fewer per pack.
Comments

One comment was received during the consultation period after publication of the agenda which supported the reclassification proposal. In New Zealand both aciclovir and hydrocortisone are already available without the need for a prescription with a well-established safety record. Internationally the combination product is available over-the-counter in over 22 jurisdictions. Recurrent herpes labialis is a common skin infection that people often seek advice at a pharmacy.

Discussion

Following a brief discussion, the Committee recommended that hydrocortisone 1% w/w should be reclassified from prescription medicine to restricted medicine when combined with aciclovir 5% w/w in primary packs of not more than 2 g for dermal use in adults or children 12 years of age and older for the treatment of herpes labialis (cold sores). Even though there was not much evidence of efficacy and a concern was raised regarding resistance, the Committee considered that the benefit to patients evidenced in the submission outweighed the risks of recommending the reclassification.

Recommendation

That hydrocortisone 1% w/w should be reclassified from prescription medicine to restricted medicine when combined with aciclovir 5% w/w in primary packs of not more than 2 g for dermal use in adults or children 12 years of age and older for the treatment of herpes labialis (cold sores).

6.2

Penciclovir – proposed reclassification from pharmacy-only medicine to general sale medicine
(Vectavir, Orion Laboratories (New Zealand) Limited)

Purpose

This was a company submission requesting the reclassification of penciclovir from pharmacy-only medicine to general sale medicine when for external use for the treatment of herpes labialis. This requested reclassification would harmonise New Zealand with Australia.

The Committee noted there were currently no other products marketed that would be affected by the proposed reclassification.

Background

At the 20th meeting on 19 November 1998, the Committee recommended that there be no change to the current pharmacy-only classification of topical aciclovir and penciclovir when indicated for herpes labialis. At the 20th meeting it was reported that penciclovir was a relatively new chemical entity and had been classified as pharmacy-only medicine because its toxicity was no greater than that of aciclovir. In 1998 it was suggested to observe the results of the use of penciclovir as a pharmacy-only medicine for at least three years before recommending a less restrictive classification.

Penciclovir is currently classified as:

  • prescription; except for external use for the treatment of herpes labialis
  • pharmacy-only; for external use for the treatment of herpes labialis.
Comments

One comment was received during the consultation period after publication of the agenda which opposed the reclassification proposal. Having penciclovir or any other medicine used to treat recurrent herpes labialis available through a pharmacy ensures the consumer receives usage information and is assessed for any risks.

Discussion

Following a brief discussion, the Committee recommended that penciclovir should be reclassified from pharmacy-only medicine to general sale medicine in preparations containing 1% or less for the treatment of herpes labialis in packs containing 10 g or less. Aciclovir is available as a general sale medicine for the treatment of herpes labialis in medicines containing 5% or less and in tubes containing 10 g or less. A lot more time than the suggested three years at the 20th meeting in 19 November 1998 had passed. Concerns were raised over resistance and inappropriate use in other areas. However, these risks were not considered enough by the Committee to outweigh the benefits of recommending that penciclovir be made available as a general sale medicine.

Recommendation

That penciclovir should be reclassified from pharmacy-only medicine to general sale medicine in preparations containing 1% or less for the treatment of herpes labialis in packs containing 10 g or less.

7

New medicines for classification

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

7.1

Patent blue V – Patent blue V 25 mg/mL solution for injection (TT50-10054)

Patent Blue V is injected subcutaneously under local anaesthesia. The usual injection site is the back of the foot or hand at the level of the first and fourth interdigital spaces. After massage and passive movement of the hand or foot, a skin incision is made transversely, or in the direction of the lymph vessel, and the stained lymph vessel is exposed. Patent Blue V is generally administered once during the lymphographic examination.

Patent Blue V is indicated for diagnostic use only, for marking:

  1. lymph vessels and arterial regions
  2. sentinel nodes before biopsy in patients with operable breast cancer.

At the 23rd meeting on 25 May 2000, the Committee recommended that radiographic contrast media should be reclassified from prescription medicines to general sale medicines. However, Patent Blue V is not a radiographic contrast agent.

A similar product currently marketed, Proveblue 50 mg / 10 mL solution for injection (TT50-9882), is classified as a prescription medicine.

The Committee was asked to consider classifying Patent Blue V as a prescription medicine.

One comment was received during the consultation period after publication of the agenda which raised concerns with classifying it as a prescription medicine. If Patent Blue V becomes scheduled as a prescription medicine, it will also not be available for use in cosmetic products or for industrial use. This is because a prescription would be necessary in order to obtain a prescription medicine. Scheduling Patent Blue V as prescription medicine would affect its availability for use as an approved colouring substance for use in foods, medicines, related products, cosmetic products, natural health products, and other possible industrial products.

The Centre for Adverse Reactions Monitoring has received 67 reports of reactions with Patent Blue V to date. 43 of the reactions reported were either anaphylactic shock, anaphylactic reaction or anaphylactoid reaction. The Committee were provided with a summary of these reports.

Following consideration of the data presented, the Committee recommended that Patent Blue V should be classified as a prescription medicine; for injection when used in diagnostic procedures (or words of similar meaning).

Recommendation

That Patent Blue V should be classified as a prescription medicine; for injection when used in diagnostic procedures (or words of similar meaning).

7.2

Emicizumab – Hemlibra 30mg/1mL, 60 mg/0.4 mL, 105 mg/0.7mL and 150 mg/1 mL solution for injection (TT50-10274, a, b, c)

Emicizumab is a humanised monoclonal modified immunoglobulin G4 (IgG4) antibody with a bispecific antibody structure bridging factor IXa and factor X produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells.

Hemlibra is indicated for routine prophylaxis to prevent bleeding or reduce the frequency of bleeding episodes in patients with haemophilia A (congenital factor VIII deficiency) with factor VIII inhibitors. Hemlibra can be used in all age groups.

Emicizumab is not classified in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

Recommendation

That emicizumab should be classified as a prescription medicine.

7.3

Evolocumab – Repatha 140 mg solution for injection (TT50-10273)

Evolocumab is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells.

Repatha is indicated in adults with primary hyperlipidaemia (heterozygous familial and nonfamilial) or mixed dyslipidaemia, as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), TC/HDL-C, ApoB/apolipoprotein A 1 (ApoA 1), very low density lipoprotein cholesterol (VLDL-C), triglycerides (TG) and lipoprotein(a) (lp[a]), and to increase HDL-C and ApoA 1:

  1. in combination with a statin or statin with other lipid-lowering therapies (eg, ezetimibe), or
  2. alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or
  3. alone or in combination with other lipid-lowering therapies in patients for whom a statin is not considered clinically appropriate.

Repatha is indicated in adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia (HoFH) to reduce LDL-C, TC, ApoB, and non-HDL-C in combination with other lipid-lowering therapies (eg, statins, LDL apheresis).

Evolocumab is not classified in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

Recommendation

That evolocumab should be classified as a prescription medicine.

7.4

Teduglutide – Revestive 5 mg powder for injection (TT50-10225)

The active ingredient teduglutide (rDNA origin) is a 33 amino acid glucagon-like peptide-2 (GLP-2) analogue manufactured using a strain of Escherichia coli modified by recombinant DNA technology.

Revestive is indicated for the treatment of adult patients with Short Bowel Syndrome who are dependent on parenteral support.

Teduglutide is classified in Australia as a prescription medicine (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

Recommendation

That teduglutide 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

Bezlotoxumab (June 2017)

Bezlotoxumab is indicated for the prevention of Clostridium difficile infection (CDI) recurrence in patients 18 years or older receiving antibiotic therapy for CDI.

Bezlotoxumab is already classified in Australia and New Zealand as a prescription medicine under the group entry of monoclonal antibodies. Bezlotoxumab is also individually classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. bezlotoxumab is a new chemical entity with no clinical / marketing experience in Australia
  2. bezlotoxumab should be prescribed by medical professionals who are familiar with the diagnosis and management of Clostridium difficile infection
  3. the most common adverse reactions following treatment with bezlotoxumab are nausea, diarrhoea, pyrexia and headache
  4. bezlotoxumab is a pregnancy Category B2 drug
  5. the potential for abuse of bezlotoxumab is unlikely.

The Committee agreed to harmonise.

Recommendation

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

8.1.2

Brexpiprazole (May 2017)

Brexpiprazole is indicated for the treatment of schizophrenia in adults.

Brexpiprazole is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. brexpiprazole is a new chemical entity with no clinical / marketing experience in Australia
  2. brexpiprazole may be related however, to aripiprazole which is available in Australia with a satisfactory risks / benefits analysis
  3. brexpiprazole is marketed overseas with satisfactory risks/benefits
  4. the potential for abuse of brexpiprazole is unlikely.

The Committee agreed to harmonise.

Recommendation

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

8.1.3

Ceritinib (March 2017)

Ceritinib is indicated as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on or who are intolerant of crizotinib.

Ceritinib is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia took advice from the Advisory Committee on Medicines Scheduling (from the 19th meeting on 15 November 2016) which comprised the following:

  1. Although there is no human data, pregnant rats and rabbits given ceritinib had increased skeletal abnormalities during organogenesis as well as a low incidence of visceral anomalies.
  2. The benefits of ceritinib use include its efficacy as a second line therapy for people who are intolerant or show disease progression with first-line therapy.
  3. The risks of ceritinib include embryofoetal toxicity at very low exposure in animals.
  4. Generally Appendix L (requirements for dispensing labels for human and veterinary medicines) would not be applied to anti-neoplastics when patients are being counselled to avoid pregnancy in the treatment period and shortly thereafter.
  5. The purpose for ceritinib is treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) where the disease has progressed on or who are intolerant of crizotinib (which has similar mechanism of action). Only a small number of patients would require ceritinib as its use is narrow (as a chemotherapeutic agent for NSCLC). Use of ceritinib will be prescribed only by specialist oncologists to patients under ongoing specialist care.
  6. Adverse events most common for ceritinib include gastrointestinal disorders (diarrhoea, nausea, vomiting, abdominal pain). Other very common adverse reactions include decreased appetite, fatigue, liver laboratory test abnormalities, abdominal pain and rash, as well as possible foetal toxicity.
  7. Antineoplastic agents are not routinely included in Appendix L (requirements for dispensing labels for human and veterinary medicines) or Appendix D (additional controls on possession or supply of poisons included in Schedule 4 or 8) with pregnancy warnings despite teratogenicity and other foetal abnormalities being a common concern with this class of drugs. The dosage formulation is 150 mg oral capsules taken daily, and its use will be closely monitored by specialists. Therefore, the issue of pregnancy should be raised by treating clinicians.

The Committee agreed to harmonise.

Recommendation

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

8.1.4

Dengue Vaccine (March 2017)

Live attenuated chimeric dengue virus (serotypes 1, 2, 3 & 4) is indicated for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4 in individuals 9 through 60 years of age living in endemic areas.

Dengue Vaccine (live attenuated chimeric dengue virus (serotypes 1, 2, 3 & 4)) is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. it is a new chemical entity with no marketing experience in Australia
  2. the proposed indication for the CYD dengue vaccine is for the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4 in individuals 9 through 60 years of age living in endemic areas, living in endemic areas would require medical assessment
  3. the approved dose is as a suspension for injection
  4. the potential for abuse of live attenuated chimeric dengue virus (serotypes 1, 2, 3 & 4) is unlikely.

Sanofi Pasteur’s dengue vaccine (Dengvaxia (CYD-TDV) has been registered in nineteen countries: Argentina, Australia, Bangladesh, Bolivia, Brazil, Cambodia, Costa Rica, El Salvador, Guatemala, Honduras, Indonesia, Malaysia, Mexico, Paraguay, Peru, The Philippines, Singapore, Thailand and Venezuela. The Committee noted that the World Health Organisation recommends that countries should consider introduction of the dengue vaccine CYD-TDV only in geographic settings (national or subnational) where epidemiological data indicate a high burden of disease.

The Committee agreed not to harmonise because it is already classified as a prescription medicine in New Zealand under the group entry of vaccines.

Recommendation

That dengue vaccine should not be added to the New Zealand Schedule as a prescription medicine.

8.1.5

Dupilumab (June 2017)

Dupilumab is indicated for the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupilumab can be used with or without topical therapy.

Dupilumab is already classified in Australia and New Zealand as a prescription medicine under the group entry of monoclonal antibodies. Dupiloumab is also individually classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. dupilumab is a new chemical entity with no clinical experience in Australia
  2. dupilumab is intended to treat moderate to severe atopic dermatitis
  3. there is potential for increased infection, possible interference with immune response to vaccines and a theoretical risk that it may increase potential for malignancy
  4. the potential for abuse of dupilumab is unlikely.

The Committee agreed to harmonise.

Recommendation

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

8.1.6

Fosfomycin (June 2017)

The proposed indications for fosfomycin (with trometamol) is for treatment of acute uncomplicated lower urinary tract infections, caused by pathogens sensitive to fosfomycin, in women above 12 years of age and for prophylaxis of urinary tract infections in surgical or diagnostic procedures involving the lower urinary tract in adult males and females.

Fosfomycin is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. it is a new chemical entity with no clinical experience in Australia
  2. the potential for abuse of fosfomycin is unlikely.

The Committee agreed to harmonise.

Recommendation

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

8.1.7

Guanfacine (March 2017)

Guanfacine hydrochloride is a central alpha2A-adrenergic receptor agonist and is indicated for the treatment of Attention Deficit Hyperactivity Disorder in paediatric patients (children and adolescents 6-17 years old inclusive).

Guanfacine is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia took advice from the Advisory Committee on Medicines Scheduling (from the 19th meeting on 15 November 2016) which comprised the following:

  1. Guanfacine is a central alpha2A-adrenergic receptor agonist used in the treatment of Attention Deficit Hyperactivity Disorder in children and adolescents.
  2. Guanfacine hydrochloride carries a significant risk of causing sedation and somnolence in humans exhibited by a medicine in normal use. Data demonstrates impairment of critical motor reflexes and cognitive skills applicable to driving or the operation of machinery with guanfacine hydrochloride use and therefore there is a need to warn users of any potential danger of the medication.
  3. There are no products containing guanfacine hydrochloride currently registered in the Australian Register of Therapeutic Goods. This is a prescription-only medicine and Appendix K (drugs required to be labelled with a sedation warning) sedation warning is appropriate.
  4. Guanfacine hydrochloride has no known potential for abuse or dependence. The current sedation warning statements are more appropriate for a medication used in adults rather than children and adolescents.

The Committee agreed to harmonise.

Recommendation

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

8.1.8

Meningococcal Group B Vaccine (March 2017)

Meningococcal Group B Vaccine is indicated for individuals ten years and older for active immunisation to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B.

Meningococcal Group B Vaccine is already classified in Australia and New Zealand as a prescription medicine under the group entry of Meningococcal Vaccine. From 1 June 2017, Meningococcal Group B Vaccine is also classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. Meningococcal Group B Vaccine is a new chemical entity with no clinical and marketing experience in Australia
  2. the proposed indication is for individuals 10 years and older for active immunisation to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroup B
  3. the potential for abuse of Meningococcal Group B Vaccine is unlikely.

Three comments were received during the consultation period after publication of the agenda which supported the reclassification proposal. In New Zealand meningococcal vaccine is classified as a prescription medicine; except when administered to a person 16 years of age or over by a registered 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. All three comments supported the same exception for Meningococcal Group B Vaccine. Data on the benefit in New Zealand and information about efficacy, safety dosage and administration was provided.

The Committee agreed not to harmonise. One member commented that at future meetings it would be useful to consider the classification of vaccines in other jurisdictions, not just Australia.

Recommendation

That Meningococcal Group B Vaccine should not be added to the New Zealand Schedule as a prescription medicine.

8.1.9

Migalastat (June 2017)

Migalastat is indicated for long-term treatment of adult and adolescent patients 16 years and older with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) and who have an amenable mutation.

Migalastat is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. migalastat is a new chemical entity with no marketing experience in Australia
  2. the proposed indication for migalastat is for long-term treatment of adult and adolescent patients 16 years and older with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency) and who have an amenable mutation
  3. Fabry disease is a rare disease associated with serious health risks. Treatment should be supervised by a specialist physician experienced in the diagnosis and management of Fabry disease
  4. treatment with migalastat requires clinical evaluation and monitoring by a medical practitioner
  5. labelling needs to comply with the requirements for a prescription only medicine
  6. the potential for abuse of migalastat is low.

The Committee agreed to harmonise.

Recommendation

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

8.1.10

Panobinostat (March 2017)

Panobinostat lactate, in combination with bortezomib and dexamethasone, is indicated for the treatment of adult patients with relapsed and/or refractory multiple myeloma, who have received at least two prior regimens including bortezomib and an immunomodulatory agent.

Panobinostat is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia took advice from the Advisory Committee on Medicines Scheduling (from the 19th meeting on 15 November 2016) which comprised the following:

  1. The risk of panobinostat to a human foetus is unknown. Data suggests high risk of foetal malformation or non-viability in animal trials at half the dose used in humans.
  2. Panobinostat was registered as a Prescription-only Medicine by the Therapeutic Goods Administration in March 2016 as an adjunctive therapy in adults with refractory multiple myelomas who have not responded to treatment with at least two prior regimens, including bortezomib and an immunomodulatory agent. Therefore the potential patient population is low.
  3. The product contains a boxed warning to alert prescribers and consumers to the potentially multiple and severe toxicities that may occur with this medicine. The indication was restricted to those with very limited remaining treatment options and includes the following statement: Treatment should be initiated and monitored by a specialist with experience in treating haematological malignancies.
  4. Generally, Appendix L (requirements for dispensing labels for human and veterinary medicines) would not be applied to anti-neoplastics when patients are already being counselled to avoid pregnancy in the treatment period and shortly afterwards. Antineoplastic agents are not routinely included in Appendix L (requirements for dispensing labels for human and veterinary medicines) or Appendix D (additional controls on possession or supply of poisons included in schedule 4 or 8) with pregnancy warnings despite teratogenicity and other foetal abnormalities being a common concern with this class of drugs.

The Committee agreed to harmonise.

Recommendation

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

8.1.11

Sebelipase alfa (March 2017)

Sebelipase alfa is indicated for long-term enzyme replacement therapy in patients of all ages with lysosomal acid lipase deficiency.

Sebelipase alfa is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. it is a new chemical entity with no clinical experience in Australia apart from clinical trials
  2. the risks and benefits of sebelipase alfa have been considered and are outlined in the product information and the evaluation reports
  3. sebelipase alfa is indicated for long-term enzyme replacement therapy in patients with lysosomal acid lipase deficiency
  4. it has no previous experience of use in Australia outside the clinical trial setting but has recently been approved overseas
  5. sebelipase alfa is a recombinant human lysosomal acid lipase given by intravenous infusion – its use requires medical intervention, evaluation and monitoring by a medical practitioner
  6. labelling needs to comply with the requirements for an injectable prescription only medicine
  7. it does not appear to produce dependency and the abuse potential appears low.

The Committee agreed to harmonise.

Recommendation

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

8.1.12

Silodosin (March 2017)

Silodosin is indicated for the relief of lower urinary tract associated with benign prostatic hyperplasia in adult men.

Silodosin is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia did not consult the Advisory Committee on Medicine Scheduling, but decided on a classification of prescription medicine for the following reasons:

  1. silodosin is a new chemical entity with no clinical experience in Australia
  2. the risks and benefits of silodosin have been considered and are outlined in the product information, Delegate's request for Committee advice and the evaluation reports
  3. silodosin has no previous experience of use in Australia but has been available for several years internationally
  4. silodosin is proposed for use in the hospital and community, however the majority of use will be in the community
  5. treatment should be initiated by a medical practitioner – silodosin has risks that require medical intervention, evaluation and monitoring by a medical practitioner
  6. labelling needs to comply with the requirements for a prescription only medicine
  7. it does not appear to produce dependency and the abuse potential appears to be low.

The Committee agreed to harmonise.

Recommendation

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

8.1.13

Tianeptine (March 2017)

Tianeptine is considered as an anti-depressive agent and is used for the treatment of major depressive disorder.

Tianeptine is classified as a prescription medicine in Australia (in the Standard for the Uniform Scheduling of Medicines and Poisons, October 2017).

The Committee noted that the Delegate in Australia took advice from the Advisory Committee on Medicines Scheduling (from the 19th meeting on 15 November 2016) which comprised the following:

  1. Clinical data suggest tianeptine as an effective antidepressant. It is used in 66 countries, but not in New Zealand, Canada, United Kingdom or the United States. In Singapore, tianeptine is only prescribed by psychiatrists. It is not registered or marketed in Australia. It is not in any products listed on Australian Register of Therapeutic Goods and is not listed in Therapeutic Goods (permissible ingredients) Determination. Tianeptine is however freely available in Australia via websites where it is reportedly advertised as bulk powder.
  2. Tianeptine has a short half-life requiring three times daily dosing, so its use is likely to be very limited in a well-saturated market of once-a-day antidepressants. Glutamatergic pathways, in which tianeptine acts, may become important in future as research for cognitive enhancement and when neuroprotection develops. These pathways may also become an alternative antidepressant target for special populations (eg, treatment resistant populations). Tianeptine has a wide therapeutic margin with minimal toxicity reported at very high doses.
  3. The benefits of tianeptine include its use as an antidepressant with other potential medical uses.
  4. The risks include misuse. It is apparently relatively uncommon and is apparently used for anxiolytic effect.
  5. In relation to potential for abuse, there are reports of opioid-like euphoria effects (from mu-agonist activity) at high doses (much higher than antidepressant effect eg, 300–500 mg/day). There are some reports of abuse potential overseas and reports of ‘doctor-shopping’ in France, where 28 days’ supply restrictions apply. Given this, tianeptine is recommended to have an Appendix D, item 5 listing (poisons for which possession without authority is illegal).

The Committee agreed to harmonise.

Recommendation

That tianeptine 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)

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 – March 2017


Decisions also included under agenda item 8.1.

 

a. Cetirizine

Cetirizine hydrochloride should be reclassified from Schedule 2 (pharmacy-only medicine) to unscheduled (general sale medicine) when in preparations for the treatment of seasonal allergic rhinitis in adults and children 12 years of age and over, when in a maximum pack size of 10 days’ supply labelled with a recommended daily dose not exceeding 10 mg of cetirizine hydrochloride.

The Committee noted that the Delegate in Australia took advice from the Advisory Committee on Medicines Scheduling (from the 19th meeting on 15 November 2016) which comprised the following:

  1. Adverse events associated with use of cetirizine hydrochloride during pregnancy or breastfeeding have been documented as low or nil and is managed through Required Advisory Statements for Medicine Labels. Increased benefit of increasing access to supply for indication, which is easy for consumers to self-diagnose, and improves patient autonomy. Rescheduling will align with other recent decisions for chemicals with a similar toxicological profile (loratadine and fexofenadine).
  2. The symptoms of seasonal allergic rhinitis are easy for consumers to detect and self-diagnose and are generally short-term. It is noted that cetirizine hydrochloride may be used for other allergic disorders. However, this is unlikely to be problematic.
  3. Risks of cetirizine hydrochloride use include slight potential increase in somnolence compared with other less-sedating antihistamines. These effects are unlikely to be significant at the proposed doses. Adverse events associated with use during pregnancy/breast feeding have been documented but are negligible and managed by Required Advisory Statements for Medicine Labels requirements.
  4. Cetirizine hydrochloride requires a sedation warning, and dose is limited to 10 mg daily for use in adults and children 12 years of age and older.

In New Zealand, at the 8th meeting on 6 December 1991, the Committee recommended that cetirizine be classified as a prescription medicine.

At the 9th meeting on 28 May 1992, the recommendation was for cetirizine to be classified as pharmacy-only.

At the 15th 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 17th 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 46th meeting on 15 November 2011, the Committee recommended that cetirizine hydrochloride 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 and that Medsafe should review the labelling to ensure that the cetirizine hydrochloride pack was brought into line with the loratadine pack.

At the 52nd meeting on 21 October 2014, the Committee recommended that there should be no change to the classification of cetirizine.

Cetirizine is currently classified as:

  • prescription; except for oral use
  • pharmacy-only; for oral use except in divided solid dosage forms for oral use containing 10 mg 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 mg 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.

The Committee noted there were currently 11 products marketed that would be affected by the proposed reclassification.

One comment was received during the consultation period after publication of the agenda which opposed the reclassification proposal because increasing the pack size has the potential to be a risk to public safety and result in poor patient outcomes.

The Committee agreed that it was difficult to harmonise without seeing the full submission and data set considered in Australia. Fexofenadine is already available in pack of 10 days’ supply.

Recommendation

That cetirizine should not be reclassified from Schedule 2 (pharmacy-only medicine) to unscheduled (general sale medicine) when in preparations for the treatment of seasonal allergic rhinitis in adults and children 12 years of age and over, when in a maximum pack size of 10 days’ supply labelled with a recommended daily dose not exceeding 10 mg of cetirizine hydrochloride.

8.2.2

Decisions by the Delegate – May 2017


Decisions included under agenda item 8.1.

8.2.3

Decisions by the Delegate – June 2017


Decisions included under agenda item 8.1.

9

Agenda items for the next meeting

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

  1. the future of the Committee and how it will function under the new therapeutic products regulatory regime (a number of points for discussion were highlighted – continuing with the transparency of the Committee, increasing engagement with the health sector, concerns that the number of submissions will reduce due to the commercial sensitivity of publishing training tools and references (submissions over the past few years have typically come from Green Cross Health as opposed to product sponsors), and a consideration of prescriber rights).
  2. a Medsafe paper summarising all medicines in Schedule 1 of the Medicine Regulations 1984 that reference the manufacturer’s original pack and the Committee deliberations behind each reference (generally pharmacists feel there is no need for a requirement of being sold in the manufacturer’s original pack in a classification statements because pharmacists have been repackaging for years and it is part of their good practice to do so, where as general practitioners feel that repackaging increases the risk for the patient because they do not receive the pack insert or pack detailing important safety information).

10

General business

10.1

Articles for information

The Committee were presented with the following for information:

  1. Gauld N. 2017. Short Communications: Oral contraceptives in New Zealand pharmacies. Clinical Pharmacist 9(4): 106.
  2. Gauld N. 2017. Why the resurgence of OTC reclassifications in the UK is a good thing. Clinical Pharmacist. 9(5): 130-132.
  3. MHRA. 2017. Maloff Protect antimalarial tablets to be available to buy from pharmacies. URL: www.gov.uk/government/news/maloff-protect-antimalarial-tablets-to-be-available-to-buy-from-pharmacies (accessed 3 November 2017.
  4. PHARMAC. 2017. Update to the funding of influenza vaccine via pharmacies. URL: www.pharmac.govt.nz/news/notification-2017-06-13-influenza-pharmacy/ (accessed 3 November 2017.
  5. Woman dies from accidental overdose on paracetamol, coroner finds. Stuff, 25 July 2017.

11

Date of next meeting

To take place on a Tuesday in April 2018. The Secretary would email members for their availability.

There being no further business, the Chair thanked members and guests for their attendance and closed the meeting at 12:50 pm.

This document was prepared and written by
Andrea Kerridge
the Medicines Classification Committee Secretary