1

Welcome

The Chair opened the 54^th meeting at 9:37 am and welcomed the new member, current members and guests.

2

Apologies

No apologies were received.

3

Confirmation of the minutes of the 53^rd meeting held on Tuesday 5 May 2015

The minutes of the 53^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

The Chair explained the principles of a conflict of interest declaration to new and existing members. The Chair emphasised that members were selected as independent experts in their fields and the importance of maintaining independent decision making especially if members have multiple professional roles. He explained that for these reasons, committee members needed to ensure transparency in their decisions by declaring potential conflicts of interest. A member raised a question about the confidentiality of the meeting papers and discussions undertaken. The Chair advised all members should read the spokespersons protocol in the Handbook.

The Conflict of Interest forms were returned to the Secretary.

The following conflicts of interest were declared:

1. Dr K Baddock declared that she is the deputy chair of NZMA and a member of the Medical Council of New Zealand. After discussion, the Committee decided that Dr Baddock could fully participate in the meeting as her offices are independent of her role as a committee member.
2. Mrs A Harwood declared that she is the director of Port Chalmers Pharmacy and this may be a conflict of interest of agenda item 5.1.1 oral contraceptives. After discussion, the Committee decided that Mrs Harwood could participate in the meeting as she was not involved in the objection.

All other members declared they had no additional 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 53^rd meeting

5.1.1

Oral contraceptives – proposed reclassification from prescription medicine to restricted medicine (Green Cross Healthcare Limited)

Purpose

This was a company objection to the recommendations made at the previous meeting. The objection (PDF 222 KB, 3 pages) was made on the grounds that:

• the recommendation made was outside of the Committees guidelines.
• departure from aspects of the Members' Handbook, including the expectation that members should have 'an interest in fostering self-medication where safe and appropriate'.
• unstated conflicts of interest.
• the need to be evidence based.
• the inappropriate and unprecedented role given to the major medical organisations in a reclassification.

Background

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

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

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

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

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

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

The major reason it was declined was that the submission was not supported by a medical organisation.

Desogestrel, ethinylestradiol and norethisterone are currently classified as prescription medicines. Levonorgestrel is currently classified as:

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

Green Cross Healthcare Limited has objected to the decision made at the 53^rd meeting. The original proposal has been documented with the 53^rd meeting minutes. The objection was based on:

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

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

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

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

Comments

Thirteen comments regarding the proposed reclassification of selected oral contraceptives were received. One submission commented on why they did not support the proposal. Their reasons are as follows:

1. Oral contraceptives as a prescription medicine do not constitute a significant barrier to accessing them.
2. Any existing concerns about access can be addressed via a delegated collaborative model of prescribing under the Medicines Amendment Act 2013.
3. An important aspect of prescribing oral contraceptives is the advice and counselling about its use as well as general sexual heath, particularly for young females. In some cases, when females are requesting advice on contraception or sexually transmitted infections (STI), opportunistic medical intervention is appropriate and this will not be available in a pharmacy setting.
4. The importance of a thorough background check including a physical examination where indicated (where there is a suspected STI) to assess whether there is a risk.
5. Concerned the proposed reclassification will further fragment patient care with potentially serious consequences for patients, including unintended pregnancy or life threatening adverse events.

Twelve comments supporting the proposed reclassification were received. They were from a combination of individuals and organisations. Comments made by the supporters include:

1. The proposed reclassification would increase the accessibility of selected oral contraceptives, particularly to young females, those from a cultural background that consider the topic of sexual health taboo, those living in a rural area and those that come from a low income family.
2. Green Cross Healthcare Limited have presented an alternative option that is a collaborative approach between pharmacists with additional competencies and Family Planning and/or General Practitioners. Pharmacists will refer women to Family Planning and/or GPs for ongoing contraceptive discussions, STI checks and smear tests.
3. There are successful models of pharmacists providing medicines without a prescription. Family Planning and student health are able to distribute contraception without knowledge of the patient's medical history.
4. This is in the interest of women's health and self-management of contraception for the prevention of unintended pregnancies.
5. Pharmacists are capable and this will allow GPs to see patients with more complex needs.
6. Oral contraceptives are safe and meet the criteria for reclassification.
7. The previous decision made by the MCC was outside of their guideline; in deciding that continuity of care and absence of support from major bodies was the reason to decline the reclassification of selected oral contraceptives.
8. The concern of fragmented care is less important than the risk associated with unintended pregnancies.

Discussion

The Committee reviewed the grounds of the objection made by Green Cross Healthcare Limited. The Chair conducted a vote on the validity of the objection; consensus was upheld and the objection by Green Cross Healthcare Limited was deemed valid. The Committee discussed the original proposal against the criteria of the terms of reference, their comments are as follows:

• Patient access
  1. The Committee discussed whether patient access was ideal.
  2. The Committee discussed whether there is an unmet need and whether the initial proposal would address them.
  3. One member commented that there should be an emphasis on the unmet need; the proportion of women that aren't seeking effective contraceptives and are relying on the emergency contraceptive pill (ECP) or having an abortion to avoid unintended pregnancy.
  4. The Committee discussed the proportion of women that rely on regular use of the ECP or who have terminations rather than seeking effective contraception such as the OCP.
  5. The impact of the proposal on the group of women not currentlyseeking oral contraception was discussed. The Committee was concerned that the proposal appears to be more of a convenience factor for current oral contraceptive users.
  6. One member raised the possibility of promoting the use of the 'Manage my health' portal to gain electronic access to repeat prescriptions of selected oral contraception. A member expressed the opinion that the benefit a consumer would obtain from a pharmacist consultation would be greater than that associated with receiving a repeat prescription from an electronic portal.
  7. One member highlighted a public comment that the same benefits can be delivered through standing orders.
  8. The Committee discussed the growing use of oral contraceptives in a number of cultural groups where contraception appears to be a topic of taboo. The Committee noted the growing use of oral contraception in the Pacific Island and Chinese communities where counselling increased awareness.
  9. After discussion, the Committee concluded that patient access was not a barrier to accessing OCPs.
• Accuracy
  10. The Committee discussed the initiation of treatment for oral contraceptive naïve patients during the proposed consultation process by pharmacists with additional competencies.
  11. Two members were concerned that the training programme would not be adequate and that oral contraceptive naïve patients require a comprehensive assessment.
  12. One member was concerned that while oral contraceptives are generally safe to use for majority of women there is a small proportion of women where there is a risk and a comprehensive assessment by a medical practitioner is required.
  13. Two members explained that a medical consultation focuses on the establishment of what sort of contraception is suited for the patient.
  14. Two members discussed pharmacists' capabilities to conduct the proposed consultations.
  15. The Committee discussed the availability of oral contraceptives by nurses and student health. One member commented that nurses do not prescribe for oral contraceptive naïve patients and that they perform cervical smears when necessary. The protocol for Student Health is to prescribe a 3 month supply of an oral contraceptive and to refer the student to her general practitioner.
  16. Another member highlighted that pharmacists have an in depth understanding of pharmacology and would expect this knowledge to translate to acceptable skills to prescribe oral contraceptives.
  17. The Committee discussed the prescribing of oral contraceptives in the following jurisdictions: California, Europe, and United Kingdom. The Committee noted that in the United Kingdom, nurses and pharmacists are able to prescribe oral contraceptives under certain circumstances but are required to notify the patient's general practitioner.
  18. One member commented that a protocol would be a useful tool to guide the process and also to ensure that patients with higher risk contraindications do not get lost through the system.
  19. One member commented that there is nothing in the submission that states the protocol is the only tool that guides the consultation.
• Efficacy
  20. No concerns.
• Precedent
  21. The Committee was aware that the emergency contraceptive pill is classified as a restricted medicine.
• Therapeutic index
  22. No major concerns.
• Toxicity
  23. The Committee was not aware of anything new. They were aware of all adverse reactions as they are well documented. Safety of oral contraceptives can be established with family history and asking the right questions.
• Abuse potential
  24. No concerns.
• Inappropriate use
  25. A member was concerned if patients with endometriosis were seeking oral contraceptives for self-treatment without disclosing their full medical history. They also expressed concern for patients with undiagnosed endometriosis who were using the pill, ceased use and presented with symptoms that would not be recognised as endometriosis till much later.
• Precautions
  26. No concerns.
• Communal harm and/or benefit
  27. Three members commented on the risk of fragmentation of care in the absence of electronic records and lack of communication between pharmacy and medical professionals.
  28. One member made the comment that the current manual process of pharmacists forwarding on patients information with patient consent to general practice was not ideal but had value. The process could be improved with electronic records.
  29. In their experience, the Committee discussed the group of women who do not use effective birth control and are increasingly relying on ECP and termination. Although there is no evidence that access in pharmacy will address this, the proposed options do not present a greater risk of harm.
  30. The Committee expressed interest in monitoring the proposed change in classification.
  31. The Committee noted that the submission lacked detail about the training programme. There was no detail regarding who would be responsible for maintaining and enforcing the provisions under which a pharmacist with additional competencies could prescribe selected oral contraceptives. The Committee discussed the requirements of the training programme and indicated it must be an accredited training programme with refresher courses.

After the Committee discussed the original proposal submitted at the 53^rd meeting, the Chair took the proposal to vote. The proposal did not achieve consensus or majority support from the Committee and the proposal was once again rejected.

The Committee considered that the proposed treatment protocol did not manage the risks associated with oral contraceptives in patients being prescribed these medicines for the first time.

Oral contraceptive naïve patients require a comprehensive assessment and a degree of oversight.

The Committee then discussed whether to consider the alternative proposal provided by Green Cross Healthcare Limited for this meeting. The Committee noted that the alternative proposal included in the submission was within the material released for public consultation prior to the meeting and the Committee had received submissions on the proposal from several organisations. The Committee therefore agreed that it was appropriate to consider the alternate proposal put forward by Green Cross Healthcare Limited.

The alternative proposal is a collaborative approach between pharmacists with additional competencies and Family Planning and/or GPs to limit the provision of oral contraceptives as restricted medicines only to women who have previously been prescribed an oral contraceptive.

1. The Committee noted that the alternative proposal had partial support from RANZCOG. The RANZCOG supported the repeat prescribing of oral contraceptives by pharmacists with additional competencies to woman who are a previous oral contraceptive user as set out in scenarios 1-5 in their submission.
2. One member commented on the reasoning behind RANZCOG's decision and wanted to know how they reached this decision. RANZCOG's decision indicated that a risk-benefit analysis had been completed and this member wanted this information.
3. Several members noted that concerns about fragmentation of care also applied to the alternative proposal. However, the alternate proposal's protocol which encourages communication between pharmacy and medical professionals with regards to obtaining patients consent for the sharing of patient information, especially in the absence of electronic records, was seen as an appropriate risk mitigation tool.
4. One member raised the concern that the alternative proposal did not address the proportion of women that do not present to general practitioners (unmet need).
5. The Committee noted that the alternative proposal did not have a timeframe on the prescribing of selected oral contraceptives.
6. The Committee considered that a pharmacist may prescribe oral contraceptives within a three-year period from the date of a previous medical practitioner prescription, providing that there were mechanisms in place to ensure it was not dispensed to women for whom it was now contraindicated.
7. The Committee expressed concern with regards to the development of a medical condition in the time since the initial medical assessment. The Committee concluded that this risk could be mitigated if the treatment protocol reminded Pharmacists to ensure that women had not developed medical conditions since their last medical consultation which would mean the OCP was now contraindicated. The protocol should require Pharmacists to seek information on a number of conditions, listed as contraindications in the product data sheets, including:
   1. New or worsening headaches
   2. Changes in patterns of migraine
   3. New symptoms of cardiovascular disease
   4. Commenced smoking
   5. Women younger than 16 years in age
   6. Recently diagnosed (or close relative) with breast cancer, heart or kidney problems, epilepsy, hypertension, depression
   7. Planning to undergo major surgery
   8. Immobilised
   9. Pregnant or likely to be pregnant
8. Women with newly identified contraindications would then be referred to their primary healthcare provider for further assessment and discussion on optimum methods of contraception.
9. The Committee discussed the supply of the selected OCPs as restricted medicines. The Committee indicated that selected oral contraceptives were to be supplied:
   1. in a pack approved as a restricted medicine
   2. with an explanation of possible side effects and encouragement to seek medical advice as described in the patient information leaflet and datasheet.
   3. encourage regular cervical screening and blood pressure checks etc.
   4. in no more than a six months' supply
10. The Committee considered that a pharmacist may prescribe oral contraceptives within a three-year period from the date of a previous medical practitioner prescription, providing that there were mechanisms in place to ensure it was not dispensed to women for whom it was now contraindicated.

Recommendation

That the selected oral contraceptives (desogestrel, ethinylestradiol, norethisterone and levonorgestrel) should be reclassified as restricted medicines, when sold in the manufacturer's original pack containing not more than six months' supply by a registered pharmacist who has successfully completed a training programme (endorsed or accredited by an organisation that is to be confirmed as stated in the following recommendation), when indicated for oral contraception in women who have previously been prescribed an oral contraceptive within the last 3 years from the date of an original medical practitioner's prescription.

That Green Cross Healthcare Limited should provide Medsafe with details of who will be responsible for accrediting the training programme and maintaining and enforcing the provisions under which a pharmacist with additional competencies could prescribe selected oral contraceptives.

That Green Cross Healthcare Limited should update Medsafe of the changes required to the training and monitoring procedures to reflect the Committee's recommendations.

That market sales should be collected and analysed to monitor the success of the scheme in improving access to oral contraceptive pills. The Committee is interested in being updated on the outcomes of this recommendation.

5.2

Matters arising for information

5.2.1

Update to the First Schedule to the Medicines Regulations 1984

6

Submissions for reclassification

6.1

Influenza vaccine – extension of influenza vaccination by pharmacists
(Green Cross Healthcare)

Two representatives of the sponsor observed the discussion but left the meeting room before a final recommendation was made.

Purpose

This was a company submission to extend the prescription medicine classification of Influenza vaccine for the treatment and prevention of influenza to allow for the administration of the vaccine by pharmacists who have completed an approved course, to children 13 years and over.

Background

Green Cross Healthcare Limited have made a submission to extend the classification of Influenza vaccine from

prescription medicine except when administered to a person 18 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, to

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.

The submission documentation provided by Green Cross Heathcare Limited focused on the following points:

• Internationally growing acceptance and trend
• Convenience of getting family vaccinated without an appointment
• Vaccinating young teenagers reduces the spread of influenza and the cost and time of a parent having to take time off work
• A summary of benefits of the proposed reclassification with regards to the terms of reference.

The influenza vaccine was discussed at the 47^thand the 50^th meeting. It was also discussed at the 43^rd meeting agenda item 5.3 Vaccines, and 49^th meeting agenda item 5.3 Further data to support the reclassification of diphtheria, tetanus and pertussis (acellular, component) vaccine, and 5.6 Training for pharmacist vaccinators.

Currently, the influenza vaccine is classified as a prescription medicine except when administered to a person 18 years of age or older by a registered pharmacist who has successfully completed a vaccinator course approved by the Ministry of Health.

Comments

Two comments were received supporting the proposed extension of the prescription medicine classification to allow the administration of the vaccine to children 13 years of age and over by a pharmacist that has completed a vaccinator course approved by the Ministry of Health.

Discussion

The Committee assessed the proposal against the criteria under the Terms of Reference.

• Patient Access
  1. The Committee discussed the impact of the proposal in increasing access of the influenza vaccine to include adolescents. Adolescents have been identified as the hardest age group to vaccinate and it would be advantageous to target them as they are main transmitters due to a longer period of viral shedding.
  2. The proposal would increase the number of influenza vaccinators during an outbreak or pandemic.
  3. The proposal would be in line with WHO guidance and government policy.
  4. One member queried why the age of 13 years was chosen and suggested enabling vaccination of even younger children would be appropriate.
• Accuracy
  5. No concerns.
• Efficacy
  6. The Committee were aware that the influenza vaccine is reasonably efficacious.
• Precedent
  
  
• Therapeutic Index
  7. No concerns.
• Toxicity
  8. One member was concerned of the risks of multiple vaccines given to the same person.
• Abuse Potential
  9. Nothing significant.
• Inappropriate Use
  10. No concerns
• Precautions
  11. One member raised awareness to allergic reactions.
• Communal harm and/or benefit
  12. One member acknowledged good communal benefit.

Recommendation

That the classification of the influenza vaccine should be extended to allow pharmacists with additional competencies, those that have completed a vaccinator course approved by the Ministry of Health, to administer the vaccine to children aged 13 years of age or over.

The Committee encouraged Green Cross Healthcare Limited to make another submission to extend the administration of influenza vaccine by a specially trained pharmacist who has completed a vaccinator course that is approved by the Ministry of Health to younger aged children.

7

New medicines for classification

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

1. Grazoprevir and Elbasvir
   
   Merck Sharp and Dohme (MSD) are proposing to seek approval for their new once-daily, single-tablet combination therapy for the treatment of adult patients infected with chronic hepatitis C virus (HCV) genotypes (GT) 1, 4 or 6.1.
   
   The tablet is a combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor).
   
   Both actives are New Chemical Entities and require classification. Grazoprevir and Elbasvir are not classified in Australia.

   Recommendation

   That grazoprevir and elbasvir should be classified as prescription medicines.
2. Nivolumab
   
   Nivolumab is a fully human anti-PD-1 monoclonal antibody which is a highly specific programmed death-1 (PD-1) immune checkpoint inhibitor and has been studied in treatment of melanoma, squamous and non-squamous non small cell lung cancer (SQ NSCLC and NS NSCLC), renal cell carcinoma (RCC) and other tumor types.
   
   Medsafe has not yet received any products containing nivolumab. However, Medsafe does expect an application for Opdivo which contains the active ingredient nivolumub, and expects the indications to be as follows:
   
   Nivolumab is indicated for the treatment of unresectable or metastatic melanoma as a single agent in patients with disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor, or in combination with ipilimumab in patients with wild-type melanoma. Nivolumab is also indicated for the treatment of metastatic non-small cell lung cancer in patients with progression on or after platinum-based chemotherapy.
   
   Nivolumab is not classified in Australia.

   Recommendation

   That nivolumab should be classified as a prescription medicine.
3. Lesinurad
   
   Lesinurad is a selective uric reabsorption inhibitor (SURI) of the urate transporters, URAT1 and OAT4. The urate transporter URAT1 is responsible for most of the uric acid reabsorption in the kidneys.
   
   Lesinurad is indicated for the treatment of hyperuricemia associated with gout, in combination with a xanthine oxidase inhibitor.
   
   Lesinurad is not classified in Australia.

   Recommendation

   That lesinurad should be classified as a prescription medicine.

7.1

Section 29 new medicines for classification

The following section 29 new chemical entities were submitted to the Committee for classification.

1. Alectinib
   
   Alectinib is an investigational medicine by Roche. Alectinib is an oral investigational anaplastic lymphoma kinase inhibitor (ALKi), indicated for patients with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC) whose disease had progressed following treatment with crizotinib. Submitted to FDA for approval in June 2013 and supplied in Japan from September 2014 (http://www.roche.com/media/store/releases/med-cor-2015-05-14.htm)
   
   Currently undergoing phase 3 studies (https://clinicaltrials.gov/ct2/show/NCT02271139)

   Recommendation

   That alectinib should be classified as a prescription medicine.
2. Amifampridine
   
   Amifampridine is marketed in the EU by BioMarin Pharmaceutical under the trade name Firdapse. It is designated as an orphan drug in the EU and it is used to treat the symptoms of Lambert-Eaton myasthenic syndrome (LEMS) in adults.
   
   Amifampridine is a potassium channel blocker, which prevents charged potassium particles from leaving the nerve cells. It is designated as a prescription medicine in Europe (http://www.drugs.com/uk/firdapse.html)

   Recommendation

   That amifampridine should be classified as a prescription medicine.
3. Artesunate
   
   Artesunate is marketed as Artsun by Guilin Pharmaceutical Co. Ltd. It has been approved by the WHO via the pre-qualification programme for the treatment of severe falciparum malaria.
   http://apps.who.int/prequal/whopar/whoparproducts/MA051part3v1.pdf
   http://apps.who.int/prequal/
   
   Artesun solution for injection has been imported regularly into New Zealand during the last 2 years.
   
   The WHO recommends the medicine is administered by qualified medical personnel which is equivalent to a prescription medicine classification in New Zealand.

   Recommendation

   That artesunate should be classified as a prescription medicine.
4. Benzbromarone
   
   Benzbromarone, a potent uricosuric drug, was introduced in the 1970s and was viewed as having few associated serious adverse reactions. It was registered in about 20 countries throughout Asia, South America and Europe. In 2003, the drug was withdrawn by Sanofi-Synthélabo, after reports of serious hepatotoxicity.
   
   Benzbromarone is currently used for treating selected cases of gout particularly for patients in whom allopurinol produces insufficient response or toxicity. (http://www.ncbi.nlm.nih.gov/pubmed/18636784)
   
   Benzbromarone is regularly supplied in New Zealand (http://www.rheumatology.org.nz/downloads/BENZBROMARONE-patient-Nov-2014.pdf).

   Recommendation

   That benzbromarone should be classified as a prescription medicine.
5. Defibrotide
   
   In Europe defibrotide is approved as Defitelio by Gentium SpA. It is is indicated for the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstruction syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy in adults and in adolescents, children and infants over 1 month of age .
   
   It is a prescription medicine in Europe.

   Recommendation

   That defibrotide should be classified as a prescription medicine.
6. Felbamate
   
   Felbamate is an anticonvulsant. It works by controlling nerve impulses in the brain, which prevents or reduces some types of seizures.
   
   An application to distribute a medicine containing felbamate (Taloxa) was received by Medsafe in 1993. After consideration by the MAAC and several requests for information, the application was withdrawn in 2000. The medicine was proposed as a prescription medicine but was not formally classified.
   
   Felbamate has a significant risk profile which means it should only be prescribed (https://www.nlm.nih.gov/medlineplus/druginfo/meds/a606011.html).

   Recommendation

   That felbamate should be classified as a prescription medicine.
7. Flunarizine
   
   Flunarizine is a calcium channel blocker, prescribed for migraine occlusive peripheral vascular disease, vertigo of central and peripheral origin and as an adjuvant in the therapy of epilepsy.
   
   It is classified internationally as a prescription medicine.
   (http://www.medindia.net/doctors/drug_information/flunarizine.htm)

   Recommendation

   That flunarizine should be classified as a prescription medicine.
8. Idebenone
   
   Idebenone, a synthetic short-chain benzoquinone and a cofactor for the enzyme NAD(P)H: quinone oxidoreductase (NQO1). It was first developed by Takeda Pharmaceuticals for use in Alzheimer's disease but may not have been commercialised. It is currently being studied by Santhera Pharmaceuticals for use in a number of orphan mitochondrial and neuromuscular indications.
   
   The reasons for import under section 29 in New Zealand are unknown.
   
   There is also some evidence that idebenone is promoted internationally as a skin rejuvenating product
   (http://www.prioriskincare.com/idebenone-about/)
   
   As there is very little information available about the risk profile of idebenone, it is prudent to consider a prescription classification.

   Recommendation

   That idebenone should be classified as a prescription medicine.
9. Nitazoxanide
   
   Nitazoxanide is an antiprotozoal agent used to treat diarrhoea in children and adults caused by Cryptosporidium or Giardia. The brand imported is Alinia, an FDA approved medicine
   (http://www.alinia.com/) and distributed in the USA as a prescription medicine.
   
   It is covered by the class entry 'antibiotic substances' but enquiries from one of the current importers suggests that they consider it to be unscheduled. For convenience a separate entry should be added for nitazoxanide given the regular imports.

   Recommendation

   That nitazoxanide should be classified as a prescription medicine.
10. Pentostatin
    
    Pentostatin is an antibiotic that is only used in chemotherapy to treat hairy cell leukemia. It is marketed internationally by Hospira under the trade name 'Nipent'. In Europe it is a prescription only medicine
    (https://www.medicines.org.uk/emc/medicine/20604).
    
    This substance is included in the class entry 'antibiotic substances' but given its specialist use in chemotherapy this may not be immediately obvious to stakeholders (e.g. NZ Customs). For convenience a separate entry should be added for pentostatin given the regular imports.

    Recommendation

    That pentostatin should be classified as prescription medicine.
11. Picibanil
    
    Picibanil is a lyophilised mixture of group A Streptococcus pyogenes with antineoplastic activity. It has been approved by in Japan since 1995 for the treatment of lymphangiomas.
    
    A short internet search failed to identify commercialisation of this medicine outside of Japan. Its uses appear to be mainly experimental
    (http://www.ncbi.nlm.nih.gov/pubmed/19029851)
    
    The risk profile of this medicine is unknown and hence should be classified as a prescription medicine.

    Recommendation

    That picibanil should be classified as a prescription medicine.
12. Rufinamide
    
    Rufinamide is an anticonvulsant used with other medication(s) to control seizures in people who have Lennox-Gastaut syndrome.
    
    The brand imported to New Zealand is Inovelon. This brand is approved in Europe as a prescription medicine and distributed by Eisai.
    (http://www.medicines.org.uk/emc/medicine/20165/SPC/)

    Recommendation

    That rufinamide should be classified as a prescription medicine.
13. Sargarmostim
    
    Sargramostim is marketed in the US by Sanofi under the trade name Leukine. It has been an FDA approved medicine since 1991. Sargramostim is a recombinant granulocyte macrophage colony-stimulating factor (GM-CSF).
    
    Leukine is used to help increase the number and function of white blood cells after bone marrow transplantation, in cases of bone marrow transplantation failure or engraftment delay, before and after peripheral blood stem cell transplantation, and following induction chemotherapy in older patients with acute myelogenous leukemia
    (http://www.leukine.com/patient-index)
    
    It is regarded as a prescription medicine in the USA.

    Recommendation

    That sargarmostim should be classified as a prescription medicine.
14. Stiripentol
    
    Stiripentol is approved as an orphan drug in Europe under the brand name Diacomit.
    
    According to the company website Diacomit is an original anti-epileptic drug resulting from BIOCODEX's research programme. Its chemical structure is not related to any other known anticonvulsant and its active substance is stiripentol.
    
    DIACOMIT® was designated as an orphan drug by the European Medicines Agency (EMA) on December 5th 2001 for its use in Severe Myoclonic Epilepsy in Infancy (SMEI).
    (http://www.diacomit.eu/).
    
    Diacomit is currently approved for use in Europe as a prescription medicine
    (http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000664/human_med_000742.jsp&mid=WC0b01ac058001d124)

    Recommendation

    That stiripentol should be classified as a prescription medicine.
15. Streptozocin
    
    Streptozocin is an alkylating agent used to treat pancreatic cancers
    (http://www.drugs.com/cdi/streptozocin.html)
    
    It is marketed internationally as a prescription medicine.

    Recommendation

    That streptozocin should be classified as a prescription medicine.
16. Tizanidine
    
    The product, Sirdalud, containing the active ingredient tizanidine is imported into New Zealand. Tizanidine is used to treat spasticity by temporarily relaxing muscle tone. It is regulated internationally as a prescription medicine.

    Recommendation

    That tizanidine should be classified as a prescription medicine.
17. Trientine hydrochloride
    
    The product, Trientine, containing the active ingredient trientine hydrochloride is imported into New Zealand by Univar.
    
    Trientine dihydrochloride, is a chelating agent indicated for the treatment of Wilson Disease in patients who are intolerant of D-Penicillamine therapy or have clinical features indication potential intolerance.
    
    It has been approved in Europe since 1985
    (http://www.trientine.com/sites/www.trientine.com/uploads/files/Trientine_SPC_Jan_2014.pdf ). It has been designated as an orphan drug by the EMA in 2003.
    
    Trientine is a prescription medicine internationally.

    Recommendation

    That trientine hydrochloride should be classified as a prescription medicine.

7.2

1,3-dimethylamylamine (DMAA) – proposed classification as a prescription medicine (Medsafe)

This is a Medsafe submission that requests classification of 1,3-dimehtylamyamine (DMAA) as a prescription medicine; except when present as an unmodified, naturally occurring substance.

DMAA is a straight chain aliphatic amine with sympathomimetic physiological effects. DMAA was first synthesised and patented in 1944 by pharmaceutical company Eli Lilly. It was originally patented as a nasal decongestant.

DMAA is currently commonly sold in dietary supplements (usually for weight loss by appetite suppression), pre-workout supplements (due to its stimulant properties) and in a range of over-the-counter party pills. DMAA is not found in any food stuff that is considered a normal part of the human diet. Therefore, it was Medsafe’s view prior to 2008 that DMAA did not meet the definition of a dietary supplement and should not be regulated under the Dietary Supplement Regulations 1985.

One comment was received supporting the proposed reclassification of DMAA to prescription medicine.

Recommendation

That 1,3-dimethylamylamine (DMAA) should be classified as a prescription medicine; except when present as an unmodified, naturally occurring substance.

7.3

Sunifiram (1-benzoyl-4-propanolypiperazine) – proposed classification as a prescription medicine (Medsafe)

This is a Medsafe submission that requests classification of sunifiram, a racetam-like substance, as a prescription medicine.

Background

At the 53^rd meeting held on 5 May 2015, it was agreed to individually classify racetam and racetam-like structures as prescription medicines as there was no suitable class entry that would describe all concerned structures.

Sunifiram (1-benzoyl-4-propanoylpiperazine) is described as a racetam-like compound. It is a piperazine derived synthetic chemical. Sunifiram does not contain the common 2-pyrolidone nucleus, but is similar to scheduled compound molracetam in that it contains a benzoyl piperazine core. Sunifiram is structurally similar to 1-benzylpiperazine (BZP), but is not captured under the Misuse of Drugs Act 1975.

Sunifiram (1-benzoyl-4 propanoylpiperazine)

An internet search of sunifiram leads to articles^{1, 2} that describe this compound as having nootropic effects in animal studies with significantly higher potency than piracetam.

Recommendation

That sunifiram 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

1. Asunaprevir
   
   Asunaprevir is an inhibitor of the NS3 serine protease of HCV, and subsequent viral RNA replication. Asunaprevir competitively inhibits the binding of substrate to NS3/4A protease complex, binding directly and reversibly to the protease, with Ki 0.24 to 1.0 nM, depending on the genotype strain employed.
   
   Asunaprevir is indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults with compensated liver disease (including cirrhosis) in combination with:
   • daclatasvir, an NS5A replication complex inhibitor, for patients with HCV genotype 1b infection.
   • daclatasvir, peginterferon alfa, and ribavirin for patients with HCV genotype 1 or 4 infection.
   In March 2015, the delegate made a final decision to include asunaprevir in Schedule 4 (prescription medicine), with an implementation date of 1 June 2015 for the following reasons:
   • It is a new chemical entity with no clinical and marketing experience in Australia.
   • asunaprevir is indicated for the treatment of chronic hepatitis C virus infection in adults with compensated liver disease (including cirrhosis) in combination with:
     • daclatasvir, an NS5A replication complex inhibitor, for patients with HCV genotype 1b.
     • daclatasvir, peginterferon alfa, and ribavirin for patients with HCV genotype 1 or 4 infection.
     • asunaprevir may cause liver toxicity. As asunaprevir is to be used in combination with other medicines, there could be adverse events caused by the concomitant medicines. Drug-drug interactions can occur when asunaprevir is co-administered with other medicines.
   • Pregnancy category B1 is acceptable for asunaprevir. When used in combination with daclatasvir (B3), or daclatasvir and peginterferon alfa and ribavirin (category X), the most restrictive category is applicable.
   • asunaprevir should be prescribed by medical professionals who are familiar with the management of chronic liver diseases. The patients need to be instructed to follow the recommended dosing regimens.
   The Committee considered harmonising with the above classification.

   Recommendation

   That asunaprevir should be classified as a prescription medicine.
2. Daclatasvir
   
   Daclatasvir is an inhibitor of the hepatitis C virus nonstructural protein 5a (NS5A) replication complex. NS5A is a multifunctional protein with key functions in both HCV replication and modulation of cellular signalling pathways.
   
   Daclatasvir is indicated, when in combination with other agents, for the treatment of chronic hepatitis C virus (HCV) infection in adults with compensated liver disease (including cirrhosis).
   
   In March 2015, the delegate made a final decision to include daclatasvir in Schedule 4 (prescription medicine), with an implementation date of 1 June 2015, for the following reasons:
   • It is a new chemical entity with no clinical and marketing experience in Australia.
   • Daclatasvir is indicated, in combination with other medicinal products, for the treatment of chronic hepatitis C virus (HCV) infection in adults with compensated liver disease (including cirrhosis).
   • Daclatasvir is to be used for a medical condition (chronic hepatitis C virus infection) that requires careful diagnosis and management by medical professionals. Drug-drug interactions can occur when daclatasvir is coadministered with other medicines.
   • Pregnancy Category B3 is proposed.
   • There are side effects associated with the use of Daclatasvir, such as diarrhoea, nausea and headache, hypersensitivity reactions, drug-induced liver toxicity, etc.
   • Daclatasvir should be prescribed by medical professionals who are familiar with the management of chronic liver diseases. The patients need to be instructed to follow the dosing regimens.
   The Committee considered harmonising with the above classification.

   Recommendation

   That daclatasvir should be classified as a prescription medicine.
3. Netupitant
   
   Netupitant is a neurokinin1 receptor antagonist.
   
   Netupitant is indicated in adult patients, in combination with palonosetron (as part of a fixed dose combination product), for the:
   • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy; and
   • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
   In March 2015, the delegate made a final decision to include netupitant in Schedule 4 (prescription medicine), with an implementation date of 1 October 2015, for the following reasons:
   • It is a new chemical entity with no marketing experience in Australia.
   • The benefits are considered to outweigh the risks at a population level.
   • It is also noted that netupitant is currently proposed for use in a fixed dose combination with palonosetron, and benefit / risk has been assessed in this context.
   • The purpose and extent of use is reflected in the indication, i.e. use in adults for:
     • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy; and
     • Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
   • The potential for abuse of netupitant is unlikely.
   The Committee considered harmonising with the above classification.

   Recommendation

   That netupitant should be classified as a prescription medicine.
4. Cholic acid
   
   Cholic acid is a bile acid and used in patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders.
   
   Cholic acid is indicated for the treatment of inborn errors of bile acid synthesis responsive to treatment with cholic acid.
   
   In March 2015, the delegate made a final decision to include cholic acid
   
   in Schedule 4 (prescription medicine), with an implementation date of 1 October 2015, for the following reasons:
   • It is a new chemical entity with no [clinical/marketing] experience in Australia.
   • This cholic acid is a synthetic version of a naturally occurring bile acid. It has a relatively good safety profile.
   • Cholic acid is intended to be used in the management of certain inborn errors of bile acid synthesis that, if untreated, result in liver failure. Its use will be in the context of long-term management of patients with a serious medical condition that requires ongoing assessment.
   The Committee considered harmonising with the above classification.

   Recommendation

   That cholic acid should be classified as a prescription medicine.
5. Levomilnacipran
   
   Levomilnacipran is a selective serotonin and noradrenaline reuptake inhibitor (SNRI). It is reported to inhibit both the norepinephrine (NE) and 5hydroxytryptamine (5HT, serotonin) reuptake with an approximate two fold more potent inhibition of NE reuptake than 5HT reuptake transporters. It is the more active enantiomer of the racemate milnacipran.
   
   Levomilnacipran is indicated for the treatment of Major Depressive Disorder (MDD) in adults.
   
   In March 2015, the delegate made a final decision to include levomilnacipran in Schedule 4 (prescription medicine), with an implementation date of 1 October 2015, for the following reasons:
   • It is a new chemical entity with no [clinical/marketing] experience in Australia.
   • This active may cause increases in heart rate and blood pressure as well as nausea, vomiting and dizziness. Less frequent adverse effects may also occur that may require assessment and management by a medical doctor.
   • It is intended for the treatment of depression, a medical condition that requires management by a healthcare professional.
   • It has side effects that may require management by a doctor.
   The Committee considered harmonising with the above classification.

   Recommendation

   That levomilnacipran should be classified as a prescription medicine.
6. Naloxegol
   
   Naloxegol is a PEGylated derivative of the mu-opioid receptor antagonist naloxone.
   
   Naloxegol is indicated for the treatment of opioid-induced constipation (OIC).
   
   In March 2015, the delegate made a final decision to include Naloxegol in Schedule 4 (prescription medicine), with an implementation date of 1 October 2015, for the following reasons:
   • It is a new chemical entity with no clinical/marketing experience in Australia.
   • This active can cross the blood brain barrier in certain medical conditions and interacts with many other medications via CYP metabolism pathways
   • Naloxegol is intended for the treatment of opioid induced constipation. It is a new chemical entity.
   • While naloxegol when used as intended has a good safety profile it can interfere with the action of other medicines and must not be given where there is a possibility of bowel obstruction. A medical assessment should be performed prior to its initial use and where there is significant abdominal pain.
   The Committee considered harmonising with the above classification.

   Recommendation

   That naloxegol should be classified as a prescription medicine.
7. Milnacipran
   
   Milnacipran is a balanced, specific, dual reuptake inhibitor of noradrenaline (NA) and serotonin (5hydroxytryptamine [5 HT]), inhibiting noradrenaline uptake with greater potency than serotonin.
   
   Milnacipran is indicated for the treatment of fibromyalgia.
   
   In March 2015, the delegate made a final decision to include
   
   milnacipran in Schedule 4 (prescription medicine), with an implementation date of 1 October 2015, for the following reasons:
   • It is a new chemical entity.
   • This active may cause increases in heart rate and blood pressure as well as nausea, vomiting and dizziness. Less frequent adverse effects may also occur that may require assessment and management by a medical doctor. It is intended for the treatment of depression, a medical condition that requires management by a healthcare professional.
   • It is intended for the treatment of a chronic pain condition that requires management by a healthcare professional.
   • It has side effects that may require management by a doctor
   The Committee considered harmonising with the above classification.

   Recommendation

   That milnacipran should be classified as a prescription medicine.
8. Ponatinib
   
   Ponatinib is the active substance in an anticancer medicine. It is used to treat adults with the following types of leukaemia:
   • chronic myeloid leukaemia (CML);
   • acute lymphoblastic leukaemia (ALL) in patients who are 'Philadelphia' chromosome positive (Ph+).
   Ponatinib is a BCRABL tyrosine kinase inhibitor that is used for the treatment of chronic, accelerated, or blast phase chronic myeloid leukaemia, or Philadelphia chromosome-positive acute lymphoblastic leukaemia, that is resistant to, or in patients who are intolerant of, prior tyrosine kinase inhibitor therapy.
   
   Ponatinib is used in patients who do not respond to dasatinib or nilotinib (other medicines of the same class); or who cannot tolerate dasatinib or nilotinib and for whom subsequent treatment with imatinib (a third such medicine) is not considered appropriate. It is also used in patients who have a genetic mutation called 'T315I mutation' which makes them resistant to treatment with imatinib, dasatinib or nilotinib.
   
   In March 2015, the ACMS recommended that Ponatinib not be listed in Appendix D, Item 1, for the following reasons:
   • Benefits: Treatment of chronic myeloid leukaemia and Philadelphia chromosome positive acute lymphoblastic leukaemia.
   • Risks: Life threatening blood clots, severe occlusion of blood vessels, cardiac failure, pancreatitis and hepatotoxicity. Possible fetotoxicity.
   • Purposes as above. Use is limited by the incidence of the diseases, adverse effects and cost.
   • Attracts a FDA "black box" warning and a "risk evaluation and mitigation strategy" in view of the above risks.
   • Oral tablets.
   • The specialised nature of this drug is such that only haematologists are likely to use it.
   The Committee considered harmonising with the above classification.

   Recommendation

   That Ponatinib should be classified as a prescription medicine.
9. Ulipristal
   
   Ulipristal is an orally active synthetic selective progesterone receptor modulator that acts via high affinity binding to the human progesterone receptor. When used for emergency contraception the mechanism of action is inhibition or delay of ovulation via suppression of the luteinising hormone (LH) surge.
   
   Ulipristal is indicated for emergency contraception within 120 hours (5 days) of unprotected sexual intercourse or contraceptive failure.
   
   In May 2015, the delegate made a final decision to include ulipristal in Schedule 4 (prescription medicine), with an implementation date of 1 June 2015, for the following reason:
   • It is a new chemical entity with no clinical or marketing experience in Australia.
   The Committee considered harmonising with the above classification.
   
   The Committee noted that the safety of ulipristal is unknown.

   Recommendation

   That ulipristal should be classified as a prescription only medicine.
   
   The Committee encourage healthcare professionals to put forward a submission for reclassification once there is useful information suggesting it should be reclassified.

8.2

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

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

8.2.1

Decisions by the Delegate – November 2014

1. Performance and image enhancing drugs
   
   In March 2015, the Delegate made a decision to include the performance and image enhancing drugs listed below to schedule 4 (prescription medicine), with an implementation date of 1 June 2015, for the following reasons:
   • There is limited information on the risks and benefits of the substances as there has been minimal use under appropriate medical supervision. Risks from misuse are considered to be similar to those associated with the misuse of growth hormone.
   • There is increasing evidence that the PIEDs are being advertised to attract a number of user markets including:
     • Strength enhancement/muscle enhancement
     • Anti-ageing
     • Fat loss
     • Injury rehabilitation
     • Libido enhancement
     • Growth hormone deficiency
   • There is the potential for the side effects associated with use of growth hormone when growth hormone secretagogues are used, particularly if the use is not under medical supervision. There are limited data on the safety of intravenous and subcutaneous use of AOD9604 and on the long-term oral use of AOD9604 in doses in excess of those used in clinical trials.
   • Many of the substances are injected. This carries additional risks compared with other routes of administration. Injections need to be administered by persons who use appropriate infection control procedures.
   • There is misuse of the substances in sport and by body builders.
   • There is evidence of involvement of organised crime in supply of the substances. The substances are offered for sale via the internet. Many of the substances are promoted as safe alternatives to traditional performance enhancing substances such as the anabolic steroids. Suppliers are making unproven assertions about the efficacy and safety of the substances.
   Performance and image enhancing drugs that were added to schedule 4 include:
   • AOD-9604 (CAS No. 221231-10-3)
   • CJC-1295 (CAS No. 863288-34-0)
   • Pralmorelin ((Growth Hormone Releasing Peptide-2) (GHRP-2))
   • Growth Hormone Releasing Peptide-6 (GHRP-6)
   • Growth Hormone Releasing Hormones *(GHRHs)
   • Growth Hormone Releasing Peptides *(GHRPs)
   • Growth Hormone Secretagogues *(GHSs)
   • Hexarelin
   • Ipamorelin
   The Committee considered harmonising with the above classification.
   
   At the 49^th meeting held on the 17 June 2013, the Committee recommended to individually add growth hormone secretagogues to the schedule. At that meeting hexarelin and ipamorelin were recommended to be scheduled as prescription medicines.

   Recommendation

   That the following performance and image enhancing drugs should be classified as prescription medicines:
   • AOD-9604 (CAS No. 221231-10-3)
   • CJC-1295 (CAS No. 863288-34-0)
   • Pralmorelin ((Growth Hormone Releasing Peptide-2) (GHRP-2))
   • Growth Hormone Releasing Peptide-6 (GHRP-6)
   • Growth Hormone Releasing Hormones *(GHRHs)
   • Growth Hormone Releasing Peptides *(GHRPs)
   • Growth Hormone Secretagogues *(GHSs)
   That new performance and image enhancement drugs should be classified by their INN name.
2. Benzydamine
   
   In February 2015, the ACMS recommended that benzydamine be exempt from Schedule 2 (pharmacy medicine) in preparations for topical use containing 3 mg or less of benzydamine in divided oral preparations and 3 mg/mL (0.3%) or less in undivided oral preparations in a pack containing 50 mL or less, with an implementation date of 1 June 2015.
   
   The ACMS also recommended that the TGA should consider whether the Required Advisory Statements for Medicine Labels (RASML) should include any requirements for benzydamine.
   
   The reasons for the recommendation comprised the following:
   • Minimal risk of masking a condition with short-term use. Risk of substance is such that unscheduled status is acceptable and there is a potential benefit in wider access.
   • Surgery and radiation therapy are managed interventions and under clinical supervision.
   • Established safety profile of benzydamine in preparations for topical oral use.
   • Limited potential for abuse/misuse.
   The Committee considered harmonising with the above classification.

   Recommendation

   That benzydamine for topical and external use should be classified as general sale medicines.
3. Pantoprazole
   
   In February 2015, the ACMS recommended that a new entry in Schedule 2 (pharmacy medicine) for pantoprazole when supplied in oral preparations containing 20 mg or less of pantoprazole per dosage unit for the relief of heartburn and other symptoms of gastro-oesophageal reflux disease, in packs containing not more than 7 days of supply, with an implementation date of 1 June 2015.
   
   The reasons for the recommendation comprised the following:
   • Short term use of pantoprazole for the treatment of heartburn and other symptoms of gastro-oesophageal reflux disease is likely to be safe and effective.
   • Heartburn and other symptoms of gastro-oesophageal reflux disease are common. Other agents for the same indication are available as Schedule 2 medicines or are exempt from scheduling.
   • The proposed labelling and provision of Consumer Medicine Information would help ensure appropriate use of the product.
   • Pantoprazole may be more effective in treatment of gastro-oesophageal reflux disease than ranitidine which is currently available as an unscheduled medicine in a 7 day pack and as a Schedule 2 medicine in a 14 day pack.
   The Committee considered harmonising with the above classification.

   Recommendation

   That pantoprazole should remain classified as a pharmacy only medicine in divided solid dosage forms for oral use containing 20 milligrams or less with a maximum daily dose of 20 milligrams for the short-term symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and over when sold in the manufacturer's original pack containing not more than 28 dosage units.
4. Cyclizine
   
   In February 2015, the ACMS recommended that the Schedule 3 (pharmacist only medicine) entry for cyclizine be amended to specify divided preparations with a pack size limit of six dosage units, with an implementation date of 1 June 2015.
   
   The ACMS recommended an implementation date of 1 June 2015.
   
   The reasons for the recommendation comprised the following:
   • A maximum pack size of six dosage units is proposed for cyclizine in Schedule 3, due to the potential for abuse (and the recommended dosage and short-term duration of use). A six tablet pack is sufficient for the agreed dose for cyclizine HCl 50 mg tablets and the short term treatment of motion sickness. Inclusion of a pack size limit is consistent with requirements for pack size limits in the SUSMP for other OTC antihistamines for use for motion sickness, and in ARGOM for other OTC antihistamine products with abuse potential (Schedule 3 antihistamines indicated for use in insomnia). All these products are intended for short term use only.
   • There are currently no registered Schedule 3 cyclizine preparations. The only cyclizine product currently on the ARTG is a Schedule 4 injection (for prevention of nausea and vomiting, post-operatively).
   • Potential for adverse effects as a result of accumulation of cyclizine on repeated dosing (due to long half-life).
   • Cyclizine in oral preparations is currently Schedule 3 (rather than Schedule 2, as for other antihistamines with antiemetic indications) due to its abuse potential. No history of abuse is noted in Australia (no oral cyclizine products are registered), but there have been reports of abuse of OTC cyclizine products by opiate users in New Zealand (tablets are dissolved in water and injected, usually with methadone), and reports of abuse of cyclizine by methadone users in the UK.
   • The Schedule 3 entry should specify divided dose cyclizine preparations (for oral use). This would result in oral liquids being rescheduled to Schedule 4 – this is appropriate, as liquid cyclizine preparations present a greater risk of abuse than solid dose preparations, it would not affect any current products, and TGA has not considered any oral cyclizine product for use in children under 12 years.
   The Committee considered harmonising with the above classification.

   Recommendation

   That the restricted medicine entry of cyclizine should be amended to specify divided preparations sold in the manufacturer's original pack containing not more than with a pack size limit of six dosage units for oral use other than in medicines used for the treatment of anxiety or insomnia; for oral use for the treatment of anxiety or insomnia.
5. Cannabidiol
   
   In March 2015, the ACMS recommended that cannabidiol, including extracts of Cannabis sativa, and including preparations of up to 2% of cannabinoids, including cannabidivarin (CBDV), for therapeutic use, be included in Schedule 4 (prescription medicine), with an implementation date of 1 June 2015.
   
   The reasons for the recommendation comprised the following:
   • The condition that cannabidiol treats (the therapeutic use) requires diagnosis, management and monitoring under an appropriate medical practitioner.
   • Cannabidiol has a safety profile which is consistent with a Schedule 4 listing.
   • There is low risk of misuse or abuse as cannabidiol does not possess psychoactive properties.
   The Committee considered harmonising with the above classification.

   Recommendation

   That cannabidiol should be referred to the Expert Committee on Drugs as cannabidiol is classified as a class C1 controlled drug under the Misuse of Drugs Act 1975.

8.2.2

Decisions by the Delegate – March 2014

1. Hydrocortisone
   
   In March 2015, the ACMS recommended that the Schedule 3 (pharmacist only medicine) entry for hydrocortisone be amended to allow for 1 per cent 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) with an implementation date of 1 October 2015.
   
   The reasons for the recommendation comprised the following:
   • Both hydrocortisone and aciclovir at the proposed topical concentrations have been individually available at Schedule 3 or exempt from scheduling for many years without any significant public health concerns. Data indicate a risk:benefit ratio consistent with a Schedule 3 listing for combination preparations for topical treatment of herpes labialis.
   • Early access for consumers to this combination product from a pharmacist for recurrent cold sores is likely to be beneficial in reducing progression of symptoms and safe. Inclusion in Schedule 3 will mean that the product is accessed in consultation with a pharmacist for advice, education and checking appropriate use.
   • Herpes labialis can be identified by the consumer. Topical aciclovir has been exempt from scheduling for over a decade without signals indicating significant risk at this scheduling level. Mandatory pharmacist assessment at the time of sale will reduce risk where hydrocortisone is combined with aciclovir for the same indication and ensures the patient will have sufficient information about the recommended duration of use.
   • Toxicity is minimal at the proposed strength and duration of use.
   • Both ingredients have been available without prescription (at the same strengths) for more than 10 years as dermal preparations with good safety profiles and large consumer experience. It is likely that risks would be similarly low in the combination product.
   • Risks are minimised by the small pack size (2 g tube) and dermal application.
   • Combination aciclovir 5% and hydrocortisone 1% dermal cream in packs of 2 g will be used for same indication and same route of administration, dose and timing (frequency, duration) as aciclovir 5% cream.
   • The applicant's proposed labelling and Consumer Medicine Information promote appropriate use and health education.
   • Very limited abuse potential - there is the same potential for possible off-label misuse (genital herpes) as for aciclovir 5% available on general sale.
   • The combination product may be more effective in early treatment of cold sores, reducing progression rates and lesion area. Improving access to early treatment via a pharmacist reduces consumer treatment burden, and has the potential to improve self-management health outcomes. Allowing advertising to consumers would improve consumer awareness of timely access to the combination.
   One comment was received that supports the proposal to amend the restricted medicine classification of hydrocortisone.
   
   The Committee considered harmonising with the above classification.

   Recommendation

   That the Committee should defer making a decision to harmonise. The Committee requests evidence to support harmonisation.
2. Ranitidine
   
   In March 2015, the ACMS recommended that ranitidine be exempted from Schedule 2 (pharmacy medicine) when in divided preparations for oral use containing 300 mg or less of ranitidine per dosage unit in the manufacturer's original pack containing not more than seven dosage units, with an implementation date of 1 October 2015.
   
   The reasons for the recommendation comprised the following:
   • Both the 300 mg and 150 mg ranitidine products are indicated for relief of symptoms of gastro-oesophageal reflux. The 7 x 300 mg tablet packs and 14 x 150 mg tablet packs each contain the same total quantity of ranitidine - both packs would provide seven days' supply at the maximum daily dose. Once daily dosing (with 300 mg tablets) could be seen as a benefit over the twice daily dosing which may be required for efficacy with the 150 mg tablets.
   • Consumers are more likely to seek medical aid due to perceived inefficacy of a product marketed as being stronger.
   • The 300 mg dosage unit provides an easier to access dosage form of a dose that is also possible with the currently unscheduled medication, albeit one that is not recommended (for all users) by the pack instructions.
   The Committee considered harmonising with the above classification.
   
   One comment was received with regards to ranitidine and the supply of medicines in manufacturer's original pack.
   
   The Committee noted the comment. As stated in the Medicines Act 1981, medicines are to be supplied in the manufacturer's original pack as required by specific labelling guidelines.

   Recommendation

   That the general sale classification of ranitidine should be amended to include 300 milligrams or less per dose unit when sold in the manufacturer's original pack containing not more than seven dose units.

8.2.3

Decisions by the Delegate – May 2014

1. Allergens
   
   In March 2015, the Delegate made the final decision to amend the Schedule 4 (prescription medicine) entry for allergens to include "for therapeutic use", with an implementation date of 1 June 2015.
   
   The reason for the decision is that it clarifies that the Schedule 4 entry only applies to allergens used in therapeutic circumstances.
   
   The Committee considered harmonising with the above classification.
   
   The Committee noted that allergens only for therapeutic use are classified under the Medicines Act 1981.

   Recommendation

   That the prescription medicine entry for allergens remains.

9

Agenda items for the next meeting

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

1. Pack size of paracetamol

10

General Business

10.1

Article by Nadia Freeman and Paul Quigley

The Committee discussed the article by Nadia Freeman and Paul Quigley:

Freeman N and Quigley P. 2015. Care versus convenience: Examining paracetamol overdose in New Zealand and harm reduction strategies through sale and supply. The New Zealand Medical Journal. URL https://www.nzma.org.nz/journal/read-the-journal/all-issues/2010-2019/2015/vol-128-no-1424-30-october-2015/6708
(accessed 30 October 2015)

The Committee made the recommendation that Medsafe should review the pack size of paracetamol and report back to the Committee at a future meeting.

10.2

Australian Delegate's Interim decision on Codeine and letter from New Zealand Self-Medication Industry

The Committee noted the Australian Delegate's interim decision on codeine. The Committee will defer making a decision until more information becomes available.

10.3

Barriers to Accessing Prescription Medicines

The Committee noted several recent submissions alluded to barriers to accessing prescription medicines (cost, time, and convenience). Submitters indicate that an over-the-counter (OTC) classification would address access issues even though OTC medicines tend to be more expensive than subsidised prescription medicines. However, evidence was anecdotal.

The Committee considered it would be useful to see data from a comprehensive study to support the claim that reclassification would improve access rather than other options such as extending prescribing rights. The Committee deliberated and indicated that it would be useful to have a long-term strategic review of the provisions of healthcare and the role of reclassification with it.

11

Date of next meeting

The next meeting will be held on a Tuesday in April 2016.