1

Welcome

The Chair opened the 57^th meeting at 9:27 am and welcomed members and guests.

2

Apologies

Apologies were received from L Toop.

3

Confirmation of the minutes of the 55^th meeting held on Tuesday 3 May 2016

One member requested clarification on paragraph three of agenda item 10.1 - Calcium hydroxyapatite and polycaprolactone as dermal fillers. The minutes stated that dermal filler administrators are regulated under the Health and Disability Commissioner Act 1994.

It was explained that non-regulated health professionals are administered under the Health and Disability Commissioner Act 1994 because they are not designated to the Health Practitioners Competence Assurance Act 2003.

The Committee was informed that Medsafe will be re-examining the categorisation of dermal fillers. It was noted that the MHRA regulation of dermal fillers is under review https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/192028/Review_of_the_Regulation_of_Cosmetic_Interventions.pdf,
http://www.legco.gov.hk/general/english/library/stay_informed_overseas_policy_updates/cosmetic_interventions.pdf). Dermal fillers will be regulated as a medicine if it is determined that its intended action on the human body is by pharmacological or metabolic means, as outlined in the Medicines Act 1981 (the Medicines Act). Once Medsafe has completed its review, this will be added to the agenda of the next meeting.

The minutes of the 55th 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. K Miedema declared that she had previously worked with N Gauld of Natalie Gauld Ltd, who is a co-writer of the submission for agenda item 6.4 – Selected oral contraceptives.
2. K Miedema also declared that she is a co-signatory of a letter of support for selected oral contraceptives (agenda item 6.4).
   
   The Committee discussed these declarations in the absence of K Miedema. The Committee noted that the letter of support predated her appointment to the Committee. The Committee considered that K Miedema had a conflict of interest, which meant that she could remain present and answer questions during agenda item 6.4, but could not vote on this agenda item.
   
   Secretary confirmed that the Committee still had a quorum with four members, who were a balanced representation of the Committee; two Ministry members and two sector members.

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

Report on agenda items from the previous meeting

5.2

Objections made at the previous meeting

There were no objections made to the recommendations made at the 55^th meeting held on Tuesday 3 May 2016.

The 56^th meeting for Natural Health Products, which was scheduled for late September 2016 has been postponed until the Natural Health Products Bill has had its third reading in Parliament.

5.3

Updating the guidance document titled 'How to change the legal classification of a medicine in New Zealand' and other MCC processes.

At the recent 55th Medicine Classification Committee (MCC) meeting, the Committee made the recommendation that:

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

Following this recommendation, Medsafe has reviewed the current MCC processes as well as developing a proposal for an update to the decision criteria currently used.

Discussion

The Chair introduced the consultation document, which proposed an update to the guidance document titled ‘How to change the legal classification of a medicine’ as well as other committee processes. He noted that comments received expressed a diverse range of opinion. Some supported increased transparency while others supported withholding information provided to the expert committee ie, removing the consultation process.

The Committee’s discussion focused on:

1. publication of documentation including reference lists, supporting documents and appendices
2. the presence of observers at the meetings
3. the new parameters/criteria for consideration during reclassification proposals.

The Committee discussed at length, the conflicting submissions regarding transparency of the medicine reclassification process. The Committee noted that some confidentiality requests of data that are received meet the commercially sensitive criteria of the Official Information Act 1982 (OIA). This data includes product formulations, some bioequivalence data, sales strategies and unpublished data, which the Committee agreed should be withheld. The Committee agreed that public consultation of the agenda is a useful mechanism to capture other professional and professional body opinions and assessments of training tools and supporting documentation, as it can highlight aspects that may not have been considered otherwise. One member noted that there were many different healthcare practitioners involved in the administration of medicines and provisions of patient care and not all are represented on the Committee. The Committee also noted that some submitters considered that citations used to support their proposals were commercially sensitive information. The Committee agreed that for full consultations to take place, complete reference lists would need to be available in the public domain.

The Committee discussed the possibilities of making information available only by request or for a limited period, however, it was noted that the information would still be within the Ministry’s records and would be released on request under the OIA. Therefore, the Committee considered there to be limited value in restricting the release of information unless requested under the OIA as it could result in an unnecessary administrative burden for Medsafe. The Committee agreed with the purpose of the OIA to progressively increase the availability of official information to the people of New Zealand, and that any information regarding medicine classification that would otherwise be obtainable under OIA should be made permanently available on the Medsafe website. The Committee also noted that the proposal outlined in agenda item 5.4 - Medicine reclassification process could possibly enhance collaboration between appropriate professional bodies.

The Committee also noted the comments regarding one of PHARMAC’s consulting models that involves the disclosure of a summary of the proposal being considered, which is produced by PHARMAC staff. However, the Committee considered that this model would not suit the reclassification process as it would take significant resource to summarise the reclassification submissions.

The Committee considered the pilot process of having observers at the meeting. The Committee noted the comments made during consultation, some of which supported completely open meetings, and some of which supported completely closed meetings. The Committee noted the observer process of other Medsafe committees; Medicines Assessment Advisory Committee (MAAC) and Medicines Adverse Reaction Committee (MARC). Medsafe officials explained that the observer process for the MAAC was under reassessment, and that selected visitors such as academics are invited to the MARC. The Committee considered that it would be useful if Medsafe could produce a consultation paper that reviewed this process for the next meeting.

The Committee reviewed the new reclassification decision parameters proposed. Overall, the Committee was pleased with the amendments. However, it was noted that communal harm had been removed and that the replacement criteria did not appear adequate. It was explained that the intention of the removal of communal harm was due to the consideration that it was covered by other aspects of the parameters. The Committee requested that this should be made more explicit as communal harm is an important factor of the parameters. The Committee discussed the need for a risk analysis of unintended consequences to be included. The Committee discussed the addition of a risk mitigation section to provide advice on how items such as training programmes and restrictions on sale can be used to mitigate risk. The Committee also agreed that safety was an important criterion in medicine reclassification and that this should be agreed by relevant professional bodies before a reclassification takes place. The Committee recommended that the revised version of the document titled ‘How to change the legal classification of a medicine in New Zealand’ should be added to the agenda of an upcoming meeting for consultation.

The Committee also discussed who can make submissions for medicine reclassifications. The Committee disagreed with the comment received suggesting that only sponsors should be allowed to make reclassification submissions. The Committee noted that such a limitation would significantly restrict the reclassification process. Historically, submissions on medicine reclassification has been open to all and the Committee did not consider it appropriate to change this.

The Committee considered the remaining aspects of the consultation document appropriate.

Recommendation

That Medsafe should provide a final document to the Secretary in time for addition to the agenda of an upcoming meeting to allow for a full consultation.

That Medsafe should review the observer process and provide a consultation paper to the Secretary in time for addition to the agenda of an upcoming meeting to allow for a full consultation.

5.4

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

The Pharmacy Council (the Council) proposed a process for the consideration of submissions for medicine reclassifications. Under this process, any future submissions for medicines to be reclassified from prescription to restricted medicines would be reviewed against the Council's framework and a report provided to the Committee for discussion during its consideration of the application.

The process is intended to provide the Committee with information regarding pharmacist competence to safely and effectively supply a particular medicine to a patient as a restricted medicine. The framework is currently being developed in collaboration with the Pharmaceutical Society of New Zealand (PSNZ) and is designed to provide the Committee with assurance regarding Pharmacist Competence Standards, current guidelines or protocols and relevant codes (eg, Code of Ethics). The process could also enable the Council and/ or the PSNZ to provide a recommendation as to whether any formal training or up-skilling is required or whether it is within a pharmacist's current competence and knowledge. Advice around screening tools and documentation will also be provided in the reports to the Committee.

Discussion

The representatives for this submission observed a proportion of the introduction of this agenda item, and were not present for the discussion or the recommendation.

The Committee noted the proposed addition to the medicine reclassification process provided a potentially useful mechanism.

The Chair reminded the Committee that formulating training programmes was out of the Committee’s scope. The Committee noted that their role in the development of training programmes was to discuss the requirements, consider the risks of a programme and identify safety issues that should be addressed. The Committee considered that it was not necessary for it to review the final training programme.

The Committee questioned who should develop the training programmes and the content of the training material. It was considered that an integrated framework with other healthcare professionals including medical practitioners would be instrumental and provide more confidence in the programme. The Committee considered that development of pharmacy training programmes between the Council and the PSNZ was appropriately placed.

The Committee discussed the ideal level of transparency of medicine reclassification processes including the proposed additional process. The Committee informed the representatives that the proposed process would work best if the Council and the PSNZ websites contained information on classification and examples of the outcomes of previous applications the Council and the PSNZ have considered. It was noted that other information that should be available on the Council and the PSNZ websites includes useful contacts that potential submitters should consult with prior to making a submission. The Committee considered that future submissions should demonstrate that the submitter has undertaken the appropriate consultation.

The Committee discussed the scope of the proposal and its potential with the representatives of the Council and the PSNZ.

A representative confirmed the intended placement of the additional process is after the application added to the agenda and before consideration by the Committee. The representative shared that they have discussed this within the pharmacy sector that any submission wanting to down schedule would come through this process and there is a positive attitude towards its development. A representative confirmed that the intention of this proposal was for the Council and the PSNZ to review medicine reclassification submissions in order to establish and apply the appropriate rules and codes for the Committee to note alongside future submissions. That way the Committee would only need to review risks and benefits.

The representatives provided clarity on their intentions regarding confidentiality, how they intended to address confidentiality when dealing with training programmes, and whether there would be caution in addressing conflicts of interests. One Committee member considered that as the PSNZ is involved in delivering training programmes, that it was considered a potential conflict of interest. However, it was noted that this could be managed by collaborating with the Council and assessed on a case by case basis. A representative assured the Committee that any potential conflicts of interests would be managed. The representatives also confirmed regarding their intentions on confidentiality, was that some discretion would be important to be exercised, and that collaboration and transparency is important for an effective debate. The representatives shared that they were interested in the Committee’s opinion and confirmed that more transparency was welcomed.

The representatives agreed that collaboration with appropriate healthcare professions should be included in the development of training programmes.

Recommendation

That the final version of the proposed addition to the medicine reclassification process should be provided to the Secretary in time for addition to the agenda of an upcoming meeting to allow for a full consultation.

5.5

Review of codeine classification

The outcomes of the Australian Committee on Medicine Scheduling (ACMS) meeting in August 2015 were released to the Committee. The Committee reviewed the outcomes regarding the classification of codeine and signalled it would consider harmonising with the Australian Schedule.

The Committee noted harmonisation with Australia would affect the current classification of codeine. The Committee requested that the Secretary add the recommendation to the agenda of the 58th meeting to allow for a full consultation.

The Committee noted that the ACMS upscheduled codeine in its pure form or in combination, to prescription medicine, as it considered that there are safer alternatives available.

A Medsafe official stated that no abuse or misuse research had been conducted in New Zealand to indicate there was need for concern. The Committee noted that the prevalence of ibuprofen/paracetamol combination products in New Zealand may have reduced patient’s reliance on codeine for effective pain relief.

Recommendation

That an item to consider the reclassification of codeine should be added to the agenda for the 58^th meeting for the possible harmonisation with Australia of all pharmacy only entries of codeine to be amended to restricted medicine.

That Medsafe should review the relationships between the Australian and New Zealand markets, the role of codeine in cough in cold products and whether the benefit of its use outweighs the risk of harm.

6

Submissions for reclassification

6.1

Bifonazole – proposed amendment to the general sale medicine classification
(Bayer Healthcare Ltd)

Purpose

This was a submission to amend the general sale medicine classification wording of bifonazole from:

1. general sale medicine for dermal use in medicines for tinea pedis only or in shampoos containing 1% or less, to
2. general sale medicine for dermal use in medicines for tinea pedis only or in shampoos containing 1% or less or when sold in practice by a podiatrist registered with the Podiatrists Board.

Comments

Three comments were received on the proposed amendment to the general sale medicine entry of bifonazole. Two comments supported the proposal and one comment opposed the amendment.

Discussion

It was noted that the proposed submission would allow podiatrists to extend the general sale medicine use for indications other than tinea pedis.

The Committee noted other antifungal medicines that are available for supply by podiatrists, and considered the proposed amendment to the general sale classification appropriate. The Committee had no concerns with safety.

The Committee considered that there would be benefits of bifonazole supplied by registered podiatrists for indications other than tinea pedis such as the treatment of an infected toe nail.

Recommendation

That the general sale classification of bifonazole should be amended to: for dermal use in medicines for tinea pedis only or in shampoos containing 1% or less or when sold in practice by a podiatrist registered with the Podiatrists Board.

6.2

Melatonin
(Luminarie Healthcare Ltd)

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

6.3

Melatonin
(Natalie Gauld Ltd and Pharmacy Retailing (NZ) Ltd trading as Healthcare Logistics)

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

6.4

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

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 contraceptive pills (OCP) should be deferred until the results of the several ongoing studies had been published and analysed. At the time several studies claimed that low dose oral contraceptive pills containing desogestrel and gestodene presented an increased risk of thromboembolism compared to other low dose oral contraceptive pills.

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

At the 53^rd meeting on 5 May 2015, Green Cross Healthcare Ltd made a submission to reclassify selected oral contraceptives (SOCs) 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 Committee recommended that desogestrel, ethinylestradiol, levonorgestrel, and norethisterone should not be reclassified from their current schedule entries, as the submission was not supported by medical representative bodies.

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

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

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

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

7. a NZ woman who has run out of her SOC
8. a woman visiting from overseas who has run out of her SOC
9. a woman receiving the emergency contraceptive pill who was a previous SOC user
10. a woman wanting to restart contraception who was a previous SOC user
11. a woman wanting postpartum contraception who was a previous SOC user.

The Committee made the following recommendations at the 54^th meeting:

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

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

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

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

At the 55^th meeting on 3 May 2016, the Committee assessed the objection to its recommendation made at the 54^th meeting on 24 November 2014. The Committee decided that it would be best for the submitters to resubmit with a new proposal that would address all the concerns made to date.

Purpose

This was a revised submission to reclassify SOCs (desogestrel, ethinylestradiol, levonorgestrel and norethisterone) from prescription medicine to a prescription medicine except when supplied by a pharmacist who has successfully completed a training programme endorsed by the PSNZ for the supply of oral contraceptives.

The revised submission proposed a reclassification of SOCs, which could affect combined SOC pills and selected progesterone only pills (POPs). The proposed lists of SOCs contained in combined SOCs and selected POPs are provided below:

20. combined SOCs:
    1. ethinylestradiol with norethisterone
    2. ethinylestradiol with levonorgestrel
21. selected POPs:
    3. desogestrel
    4. levonorgestrel
    5. norethisterone.

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

Levonorgestrel is currently classified as:

22. prescription: 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
23. restricted: 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

The proposed classification for each substance is as follows:

24. ethinylestradiol: prescription medicine except when supplied at a strength of 35 micrograms or less in combination with levonorgestrel or norethisterone and when supplied in the manufacturer’s original pack by a pharmacist who has successfully completed a training programme endorsed by the PSNZ for the supply of oral contraception
25. levonorgestrel:
    1. prescription medicine except when supplied in the manufacturer’s original pack by a pharmacist who has successfully completed a training programme endorsed by the PSNZ for the supply of oral contraception
    2. restricted medicine 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
26. norethisterone: prescription medicine except when supplied in the manufacturer’s original pack by a pharmacist who has successfully completed a training programme endorsed by the PSNZ for the supply of oral contraceptives
27. desogestrel: prescription medicine except when not in combination and when supplied in the manufacturer's original pack by a pharmacist who has successfully completed a training programme endorsed by the PSNZ for the supply of oral contraceptives.

Other proposed requirements around the supply were as follows:

28. that there has been no break in therapy, the same formulation is continued, unless that formulation is not available in New Zealand
29. if there has been a gap in therapy or the formulation is not available in New Zealand, the therapy may change, eg, where a woman stopped treatment, had a baby and now is postpartum and breastfeeding
30. that supply can only occur if the woman is eligible for supply in accordance with the screening tool consistent with World Health Organisation's Medical Eligibility Criteria for contraceptives, and approved by the PSNZ
31. doctor referral occurs where the woman is ineligible according to the screening tool
32. a full rescreening is undertaken at first visit to a pharmacy, and annually if required
33. a maximum of six months’ supply is provided
34. the woman needs to have been prescribed an oral contraceptive in the past three years by a doctor (based on prescription or first dispensing date)
35. the woman's general practitioner (GP) is informed of the supply unless the woman opts out of this process
36. verbal and/or written information is supplied on the need for smear tests, sexually transmitted infection checks (if necessary), contraceptive options including long-acting reversible contraception, compliance, adverse effects, and what to do if a tablet is missed or diarrhoea or vomiting occur.

The Council’s protocol for the sale and supply of pharmacist only medicines for chronic conditions would also apply to the pharmacist supply of SOCs. This protocol includes:

37. face-to-face consultations when possible unless due to disability or geographical isolation within New Zealand where this is impractical
38. no pharmacist-supply to patients who reside outside of New Zealand unless a face-to-face consultation occurs
39. a requirement to exercise professional judgement to prevent the supply of medicines that are unnecessary or in excess to the patient's needs
40. electronic record-keeping of the supply of the medicine and records of the consultation
41. follow-up information is collected and added to the patient’s record
42. other health practitioners caring for the patient are referred to or consulted with if necessary and with the patient's permission
43. privacy requirements
44. the need to determine the appropriateness of the medicine
45. advising the patient using verbal and appropriate written information.

Comments

Six comments were received regarding the proposed amendment of the prescription medicine entry for SOCs to prescription medicine except when supplied by a pharmacist who has successfully completed a training programme endorsed by the PSNZ for the supply of oral contraception. Five comments were from professional bodies and one comment was from a member of the public.

Four comments supported the proposal. Common themes included:

46. a comprehensive screening tool is essential as a mechanism should be in place to refer women who do not meet the criteria to their healthcare professional
47. a collaborative approach between pharmacists and medical practitioners is encouraged
48. the proposal would increase the access to oral contraception and
49. the risk:benefit profile of these SOCs are similar to other restricted medicines.

One comment raised concerns regarding the proposal, including:

50. the proposal will prevent opportunistic medical interactions
51. there is insufficient evidence in the submission to suggest that SOCs as prescription medicines represents a barrier to access and
52. this proposal is primarily attractive to women who can afford the SOCs supplied as a medicine without a prescription rather than addressing the priority groups (young girls and women, Maori and Pasifika groups). Pharmacists would have a financial incentive for the sale of SOCs to patients, as women would only be charged for the consultation and SOCs upon supply of the medicine.

One comment did not support the proposal as is, however, it was noted there were fewer safety concerns with a change to the proposal to 12 months between prescriptions from a medical practitioner.

Discussion

The representatives for this submission observed a proportion of the introduction of this agenda item, and were not present for the discussion or the recommendation.

It was noted that the revised submission included a World Health Organisation document which reviewed the medical eligibility criteria for contraception. It was also noted that the submitters’ had addressed all material concerns raised at previous meetings.

The Committee focused on the following areas of concern:

53. the set of circumstances under which women would be eligible to receive SOCs from a pharmacist
54. the duration a pharmacist would be able to provide this service from the date of an original medical practitioner’s prescription
55. confirmation that the submitters will work with the Council and the PSNZ in finalising the training programme and an evaluation.

The Committee assessed and discussed the set of circumstances under which women may be eligible to receive SOCs from a pharmacist. The five scenarios discussed are provided below:

55. New Zealand woman who has run out of her SOCs
56. overseas woman who has run out of her SOCs
57. woman collecting ECP, and is a previous SOC user
58. woman wanting to restart contraception, and is a previous SOC user
59. woman wanting postpartum contraception, and is a previous SOC user.

The Committee discussed the switching of formulations and when this was appropriate against the proposed five scenarios. The Committee noted that a switch in SOCs would only be appropriate in two situations:

61. when a woman from overseas had run out of her SOCs, and
62. when a woman who was a previous SOC user wanted postpartum contraception.

The Committee considered that a switch in formulation was not appropriate in the other circumstances. In the circumstance where a woman had come from overseas, the Committee did not have any concerns for a switch from a formulation that was not available in New Zealand but considered that a switch should be made to a formulation that is the most similar to the originally prescribed oral contraceptive.

The Committee discussed the circumstances of a woman wanting postpartum contraception who was a previous SOC user, and had either breastfed her baby or had chosen not to breastfeed her baby.

The Committee considered an extra provision should be added to women wanting SOCs postpartum who were a previous SOC user should require a medical consultation. The Committee considered that a comprehensive medical consultation should be required as there are a number of options that would not be able to be provided by pharmacists and should be discussed. Thus, for a woman wanting SOCs postpartum who was a previous SOC user and had not breastfed her baby could be supplied with the same SOC. Whereas women wanting SOCs postpartum who were a previous SOC user but had breastfed her child could be supplied with selected POPs to give them enough time to have a consultation with a medical practitioner and decide which contraception is best.

The representatives confirmed that they understood the Committee’s concerns regarding the switching of SOCs for women who were previous SOC users and wanted postpartum contraception after breastfeeding their baby and confirmed that referrals to their medical practitioner would take place in this situation or if the women indicated they were considering other contraception options.

The Committee also noted the final recommendation made by the Australian Delegate at the Advisory Committee on Medicine Scheduling meeting in March 2015, which was no change to the reclassification of SOCs as the use of a checklist as proposed is not an adequate alternative to a comprehensive medical evaluations. However, the Committee considered that the revised submission had the potential to address all previous and present concerns.

The Chair reminded the Committee of the recommendation made at the 54^th meeting, that it had recommended the supply of SOCs for three years from the date of an original medical practitioners prescription, and that consideration of another length of period should only be considered on the grounds of new evidence.

The Committee noted the study included in the comment provided by the RNZCGP. The results of the survey, of 141 general practitioners did not highlight any new evidence with regards to the safety of SOCs. The Committee also noted that the training tool had, to an extent, accounted for any previous concerns regarding awareness and detection of sexually transmitted infections.

The Committee considered the length of period against the five scenarios and established that a:

63. one year period would be too short as it is no different from current practice
64. two year period would be insufficient when taking into account the realistic timelines of a woman wanting postpartum oral contraception
65. five year period would be too long as the Committee considered there was a higher possibility of changes in the woman’s health potentially affecting her risk.

The Committee reviewed the training tools and the two checklists provided for the combined SOCs and selected POPs. The Committee noted that these documents were still under development with the Council and the PSNZ.

The Committee requested that the programme be monitored and an evaluation be provided to the Committee as it would be interested to see the effect of the reclassification.

Recommendation

That the prescription medicine entry for selected oral contraceptives (SOC) (desogestrel, ethinylestradiol, norethisterone and levonorgestrel) should be amended to prescription medicines except 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 that is accredited by the Pharmacy Council and the Pharmaceutical Society of New Zealand, when indicated for oral contraception in women who have previously been prescribed a SOC within the last three years from the date of an original medical practitioner’s prescription and meet one of the following five scenarios with the conditions that there is no switching between selected combined oral contraceptive pill formulations, except where the formulation is not available in New Zealand as the woman has come from overseas:

1. NZ woman who has run out of her SOC
2. overseas woman who has run out of her SOC
3. woman collecting the emergency contraceptive pill who is a previous SOC user
4. woman wanting to restart contraception who is a previous SOC user
5. woman wanting postpartum contraception who is a previous SOC user.

In the case where women are previous SOC users who have been breastfeeding and are wanting postpartum contraception, they can be supplied with selected progesterone only pills and are to be referred to their medical practitioner.

That Green Cross Healthcare Limited and Natalie Gauld Ltd 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.

7

New medicines for classification

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

7.1

Betaine – proposed classification as a restricted medicine
(Emerge Health Pty Ltd on behalf of Healthcare Logistics)

This was a company submission for the classification of betaine as a restricted medicine when indicated:

1. as an adjunct in the treatment of homocystinuria
2. to decrease elevated homocysteine blood levels in patients of all age groups with:
   1. cystathionine beta-synthase (CBS deficiency) type of homocystinuria, or
   2. 5, 10-methylenetetrahydrofolate reductase deficiency (MTHFR deficiency), or
   3. cobalamin cofactor metabolism defect (cbl defect) type of homocystinuria.
3. to increase methionine and S-adenosylmethionine blood levels in patients with MTHFR deficiency and cobalamin cofactor metabolism defect (cbl defect) type of homocystinuria.

Discussion

The Committee noted that betaine is an important component in the treatment of homocystinuria. It is used in quantities of several grams per day in combination with vitamin B6, B12, folic acid, and a methionine restricted diet. Homocystinuria, reportedly affects 1 in 126,000 people in the UK.

The Committee noted that betaine is also used in some natural health products.

The Committee noted there have been several case reports of cerebral oedema in patients taking betaine, however, this adverse effect resolved when betaine treatment was stopped. It was also noted that there have been few cases of misuse in the bodybuilding industry.

The Committee noted that betaine has been supplied in New Zealand under Section 29 of the Medicines Act since October 2012, and that it has been an unscheduled medicine in Australia since October 1996.

The Committee discussed the request for a restricted medicine classification for the indications provided but noted the specialised use of betaine and the importance of administration under specialist care.

The Committee discussed classification options which would result in the scheduling of betaine for homocystinuria, while still permitting use as a dietary supplement.

The Committee noted that there was a lack of information about the abuse/misuse potential of betaine. There were no defined thresholds for betaine. This made it difficult to determine the quantities at which classification as a restricted medicine could be determined.

It was agreed that homocystinuria is not a self-diagnosable condition and therefore the Committee considered a general sale classification versus a prescription medicine classification. The general sale classification would require Medsafe to only approve medicine applications that are indicated for the treatment of homocystinuria and restricted to specialist use. However, the Committee noted that confusion could be generated for wholesalers and distributors regarding restrictions on access. The Committee considered that a prescription medicine classification was more straightforward and appropriate.

Recommendation

That betaine should be classified as a prescription medicine when indicated for the treatment of homocystinuria.

7.2

New chemical entities that are not yet classified in New Zealand

a.

Albutrepenonacog alfa

Albutrepenonacog alfa is a purified protein produced by recombinant DNA technology. It is produced by the genetic fusion of recombinant albumin to recombinant coagulation factor IX (FIX). Albutrepenonacog alfa is indicated in all patients with haemophilia B for:

1. routine prophylaxis to prevent or reduce the frequency of bleeding episodes
2. control and prevention of bleeding episodes
3. control and prevention of bleeding in the perioperative setting.

Albutrepenonacog alfa is a recombinant fusion protein linking recombinant coagulation FIX with recombinant albumin that effectively replaces the missing coagulation FIX needed for haemostasis and provides for longer dose regimens. The prolongation of the half-life of FIX and the enhanced systemic exposure are achieved by fusion with recombinant albumin. Albumin is a natural, inert carrier protein in plasma with a long half-life of approximately 20 days that is not involved in immune defence or immune response. Genetic fusion of recombinant coagulation FIX with albumin extends the half-life of FIX.

Albutrepenonacog alfa is not classified in Australia.

The Committee noted that other blood products are general sale medicines and that this classification allows blood transfusion centres to distribute the products without a pharmacist present.

Recommendation

That Albutrepenonacog alfa should be classified as a general sale medicine.

b.

Atezolizumab

Atezolizumab is an engineered, humanised, monoclonal antibody that directly binds to the protein programmed death ligand 1 (PD-L1), and blocks interactions with the programmed death 1 (PD-1) and B7.1 receptors. Atezolizumab is indicated for the treatment of patients with locally advanced or metastatic:

1. non-small cell lung cancer (NSCLC) after prior chemotherapy
2. urothelial carcinoma after prior chemotherapy or who are considered cisplatin ineligible.

Binding of PD-L1 to the PD-1 and B7.1 receptors found on T-cells suppresses cytotoxic T-cell activity through the inhibition of T-cell proliferation and cytokine production. PD-L1 may be expressed on tumour cells and tumour-infiltrating immune cells, and can contribute to the inhibition of the anti-tumour immune response in the microenvironment.

Atezolizumab is an iron-engineered humanised immunoglobulin Gl (IgGl) monoclonal antibody that directly binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors, releasing PD-L1/PD-1 pathway-mediated inhibition of the immune response, including reactivating the anti-tumour immune response. Atezolizumab leaves the PD-L2/PD-1 interaction intact, allowing PD-L2/PD-1 mediated inhibitory signals to persist. In syngeneic mouse tumour models, blocking PD-L1 activity resulted in decreased tumour growth.

Atezolizumab is not classified in Australia.

Recommendation

That Atezolizumab should be classified as a prescription medicine.

c.

Ocrelizumab

Ocrelizumab is a recombinant humanised anti-CD20 monoclonal antibody (lgG1 subtype).

Ocrelizumab is indicated for the treatment of patients with:

1. relapsing forms of multiple sclerosis to supress relapses and disease progression (clinical and subclinical disease activity)
2. primary progressive multiple sclerosis to delay disease progression and reduce deterioration in walking speed.

Ocrelizumab is a recombinant humanised monoclonal antibody that selectively targets CD20 expressing B-cells. CD20 is a cell surface antigen found on pre-B-cells, mature and memory B-cells but not expressed on lymphoid stem cells and plasma cells.

The precise mechanisms through which ocrelizumab exerts its therapeutic clinical effects in multiple sclerosis are not fully elucidated but is presumed to involve immunomodulation through the reduction in the number and function of CD20-expressing B-cells. Following cell surface binding, ocrelizumab selectively depletes CD20-expressing B-cells through antibody-dependent cellular phagocytosis, antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and apoptosis. The capacity of B-cell reconstitution and pre-existing humoural immunity are preserved. In addition, innate immunity and total T-cell numbers are not affected.

Treatment with ocrelizumab leads to rapid depletion of CD19+ B-cells in blood by 14 days post treatment (first time-point of assessment) as an expected pharmacologic effect. This was sustained throughout the treatment period. For the B-cell counts, CD19 is used as the presence of ocrelizumab interferes with the detection of CD20 by the assay.

Ocrelizumab is not classified in Australia.

Recommendation

That Ocrelizumab should be classified as a prescription medicine.

d.

Osimertinib

Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. It is indicated for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive non-small cell lung cancer.

Osimertinib is a selective and irreversible inhibitor of EGFRs which harbour single (L858R or del746-750) or double (L858R/T790M or del746-750/T790M) mutations.

In vitro studies have demonstrated that osimertinib has high potency and inhibitory activity against EGFR across a range of all clinically relevant EGFR sensitising-mutant and T790M mutant non-small cell lung cancer (NSCLC) cell lines (apparent IC_50s from 6 nM to 54 nM against phospho-EGFR). This leads to inhibition of cell growth, while showing significantly less activity against EGFR in wild-type cell lines (apparent IC_50s 480 nM to 1.8 μM against phospho-EGFR). In vivo oral administration of osimertinib leads to tumour shrinkage in both EGFRm and T790M NSCLC xenograft and transgenic mouse lung tumour models.

Treatment with osimertinib should be initiated by a physician experienced in the use of anticancer therapies.

Osimertinib is not classified in Australia.

Recommendation

That Osimertinib should be classified as a prescription medicine.

e.

Rurioctocog alfa pegol

Rurioctocog alfa pegol, pegylated recombinant human factor VIII, is a full-length form of human coagulation factor VIII (parent molecule: ADVATE [Octocog alfa, Recombinant Human Factor VIII]) with an extended half-life.

Rurioctocog alfa pegol is indicated in haemophilia A (congenital factor VIII deficiency) patients for:

1. control and prevention of bleeding episodes
2. routine prophylaxis to prevent or reduce the frequency of bleeding episodes
3. perioperative management (surgical prophylaxis).

Rurioctocog alfa pegol is not indicated for the treatment of von Willebrand disease.

The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and von Willebrand factor) with different physiological functions. When infused into a haemophilic patient, factor VIII binds to von willebrand factor in the patient's circulation. Activated factor VIII acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X. Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin and a clot can be formed. Haemophilia A is a X-chromosomal linked hereditary disorder of blood coagulation due to decreased levels of factor VIII:C and results in profuse bleeding into joints, muscles or internal organs, either spontaneously or as results of accidental or surgical trauma. By replacement therapy, the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and correction of the bleeding tendencies.

Rurioctocog alfa pegol is not classified in Australia.

The Committee noted that other blood products are general sale medicines and that this classification allows blood transfusion centres to distribute the products without a pharmacist present.

Recommendation

That Rurioctocog alfa pegol should be classified as a general sale 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.a

Alirocumab

Alirocumab is a fully human monoclonal antibody (IgG1 isotype) that specifically targets proprotein convertase subtilisin/kexin type 9 (PCSK9). Alirocumab is produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture.

Alirocumab is indicated:

1. as an adjunct therapy to diet, for long-term use in adult patients with primary hypercholesterolaemia (non-familial and heterozygous familial) to reduce low-density lipoprotein cholesterol (LDLC)
2. in combination with a statin (HMGCoA reductase inhibitor), with or without other lipid modifying therapy (LMT), in patients not appropriately controlled with a statin
3. as monotherapy, or as an add on to other non-statin LMT, in patients who cannot tolerate statins.

It was noted that alirocumab has an insignificant abuse potential. It does not produce dependency. The Committee stated they did not have any concerns about alirocumab.

Alirocumab is classified as a prescription medicine in Australia.

Recommendation

That alirocumab should be classified as a prescription medicine.

8.1.b

Armodafinil

Modafinil is a racemic mixture of the enantiomers R-modafinil and S-modafinil with the stereogenic centre at the sulphur atom. Armodafinil is R-modafinil only.

Modafinil/armodafinil are oral wakefulness promoting agents, but pharmacologically different from other stimulants (including sympathomimetic amines). The exact mechanism of action is unknown.

Armodafinil is indicated:

1. to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy
2. to treat excessive sleepiness associated with moderate to severe chronic shift work sleep disorder where non-pharmacological interventions are unsuccessful or inappropriate
3.  as an adjunct to continuous positive airways pressure (CPAP) in obstructive sleep apnoea/hypopnoea syndrome in order to improve wakefulness.

The Committee noted that armodafinil is not listed in the Misuse of Drugs Act 1975 (the Misuse of Drugs Act).

Armodafinil is classified as a prescription medicine in Australia.

Recommendation

That armodafinil should be classified as a prescription medicine.

8.1.c

Asfotase alfa

Asfotase alfa is a human recombinant tissue on specific alkaline phosphatase (TNSALP)-Fc-deca-aspartate fusion protein with enzymatic activity, produced by recombinant DNA technology using mammalian Chinese Hamster Ovary (CHO) cell culture.

Asfotase alfa is indicated for long-term enzyme replacement therapy in patients with paediatric onset hypophosphatasia.

The Committee noted that asfotase alfa is primarily used by endocrinologists for the management of bone disorders.

Asfotase alfa is classified as a prescription medicine in Australia.

Recommendation

That asfotase alfa should be classified as a prescription medicine.

8.1.d

Deoxycholic acid

Deoxycholic acid is a an adipocytolytic drug, which when injected into localized subcutaneous fat, physically disrupts the cell membrane of adipocytes and causes adipocytolysis, the destruction of fat cells.

Deoxycholic acid is indicated for the improvement in the appearance of moderate to severe convexity or fullness associated with submental fat in adults.

Deoxycholic acid is classified as a prescription medicine in Australia.

Currently, deoxycholic acid is a general sale medicine and is also in a natural health product as it is a natural component of bile sales.

The Committee noted that in its injectable form it is used for lyposysis in chins.

Recommendation

That deoxycholic acid for injection should be classified as a prescription medicine.

That deoxycholic acid in its oral form should remain as a general sale medicine.

8.1.e

Di-iodohydroxyquinoline

Di-iodohydroxyquinoline (INN) or iodoquinol (USAN) is a quinoline derivative that is used in the treatment of amoebiasis.

In Australia, di-iodohydroxyquinoline is classified as:

1. restricted medicine for vaginal use
2. prescription medicine except when a restricted medicine or for human use.

The Committee noted that quinoline derivatives:

3. are poorly absorbed in the gastrointestinal tract used and are most often prescribed for the treatment of gut amoebisis.
4. should not be used topically, orally or for amoebic dysentery in children because of risk of absorption
5. can cause severe neurotoxicity issue absorption and skin
6. also claim to have antifungal properties if used topically and acrodermatitis enteropathica.

The Committee noted that restricted medicine entry of di-iodohydroxyquinoline in Australia applies to its antifungal properties.

The Committee recalled the use of Dalacin T as a topical acne treatment.

The Committee noted that proposing to classify di-iodohydroxyquinoline as a prescription medicine for vaginal use only, would result in the unintended consequence that di-iodohydroxyquinoline would be an unscheduled medicine for all other indications. Therefore, the Committee considered it appropriate to classify di-iodohydroxyquinoline as a prescription medicine for all indications including for vaginal use.

Recommendation

That di-iodohydroxyquinoline should be classified as a prescription medicine.

8.1.f

Flubromazolam

Flubromazolam is a benzodiazepine derivative. It is a triazolo analogue of the designer benzodiazepine, flubromazepam.

Benzodiazepines enhance the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain. This results in anxiolytic, sedative, hypnotic, muscle relaxant and antiepileptic effects.

Flubromazolam has high potency, and can cause strong sedation and amnesia at oral doses as low as 500 micrograms. Flubromazolam has an onset of effect of 30 minutes, and duration of effect of 12-18 hours. After effects are experienced for ≥ 24 hours. There is a risk of fatal overdose if benzodiazepine derivatives such as flubromazolam are combined with other central nervous system depressants such as opioid analgesics, alcohol and 4-hydroxybutanoic acid (GHB).

Flubromazolam has no currently established therapeutic use and is likely to present a high risk of dependency, abuse, misuse or illicit use. The dangers associated with flubromazolam are such as to warrant limiting use to strictly controlled medical and scientific research.

Flubromazepam has a much longer time to onset of effect (four hours) and much longer duration of effect (three days) than flubromazolam.

The Committee noted the following information on flubromazolam, that:

1. there is a risk of unintended overdosing and people who use flubromazolam for its psychoactive properties reported compulsive redosing
2. abrupt discontinuation of flubromazolam following regular dosing over several days can result in a withdrawal phase that includes rebound symptoms such as increased anxiety and insomnia
3. flubromazolam has recently become available online (products available for sale online include the pure substance and 250 microgram pellets).

It was noted that flubromazolam is captured as a prescription medicine under the benzodiazepine derivatives group entry under the Medicines Regulations 1984 (the Medicines Regulations). Benzodiazepine derivatives are individually listed in Schedule 3 of the Misuse of Drugs Regulations 1975 as class C5 controlled drug.

The Committee noted the risks associated with flubromazolam and suggested scheduling it with the highest classifications available under the Medicines Act and the Misuse of Drugs Act.

Recommendation

That flubromazolam should be classified as a prescription medicine.

That flubromazolam should be referred to the Expert Advisory Committee on Drugs with the advice that it should be scheduled with a more restrictive classification than the C5 entry for benzodiazepine derivatives.

8.1.g

Follitropin delta

Follitropin delta is a novel human recombinant follicle stimulating hormone intended for controlled ovarian stimulation in women undergoing assisted reproductive technology (ART) therapy such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI).

Follitropin delta is indicated for controlled ovarian stimulation for the development of multiple follicles in women undergoing ART such as an in vitro fertilisation (IVF) or ICSI cycle.

Follitropin delta is classified as a prescription medicine in Australia.

Recommendation

That follitropin delta should be classified as a prescription medicine.

8.1.h

Hexyl Aminolevulinate

Hexyl aminolevulinate (as hydrochloride) is a hexyl ester of 5aminolevulinic acid (5ALA or ALA), which is the first specific intermediate of heme biosynthesis.

Hexyl aminolevulinate is indicated as adjunct to standard white light cystoscopy to contribute to the diagnosis and management of bladder cancer in patients with known or high suspicion of bladder cancer.

Hexyl aminolevulinate is classified as a prescription medicine in Australia.

Recommendation

That hexyl aminolevulinate should be classified as a prescription medicine.

8.1.i

Ixekizumab

Ixekizumab is a humanised monoclonal antibody against the pro-inflammatory cytokine interleukin17A (IL17A).

Ixekizumab is indicated for the treatment of adult patients with moderate to severe plaque psoriasis.

Ixekizumab is classified as a prescription medicine in Australia.

Recommendation

That ixekizumab should be classified as a prescription medicine.

8.1.j

Phleum pratense extract

Phleum pratense extract is a standardised allergen extract of grass pollen from Timothy-grass (phleum pratense).

Phleum pratense extract is indicated for:

1. allergy immunotherapy indicated for the treatment of grass pollen induced allergic rhinitis with or without conjunctivitis;
2. disease modifying treatment of grass pollen induced rhinitis and conjunctivitis;
3. and use in persons aged 5 years or older.

It was noted that all other allergens are prescription medicines.

Phleum pratense pollen extract (Timothy-grass pollen extract) is classified as a prescription medicine in Australia.

Recommendation

That phleum pratense extract should classified as a prescription medicine.

8.1.k

Tofacitinib

Tofacitinib is a janis kinase (JAK) 1, 2 and 3 kinase inhibitor with some limited inhibitory activity against tyrosine kinase 2 (TyK2).

Tofacitinib is indicated for the treatment of the signs and symptoms of moderate to severe active rheumatoid arthritis in adults who have had an inadequate response or are intolerant to methotrexate. Tofacitinib can be used alone or in combination with non-biological disease-modifying antirheumatic drugs, including methotrexate.

Therapy with tofacitinib should be initiated and monitored by a rheumatologist or specialist physician with expertise in the management of rheumatoid arthritis.

Tofacitinib is classified as a prescription medicine in Australia.

Recommendation

That tofacitinib should be classified as a prescription medicine.

8.1.l

Velpatasvir

Velpatasvir is a novel pangenotypic hepatitis C virus (HCV) non-structural protein 5A (NS5A) inhibitor for use in combination with sofosbuvir for the treatment of HCV infection.

Velpatasvir, in a fixed combination with sofosbuvir, is indicated for the treatment of chronic HCV infection in adults.

Velpatasvir is classified as a prescription medicine in Australia.

Recommendation

That velpatasvir should be classified as a prescription medicine.

8.1.m

Vorapaxar

Vorapaxar is an inhibitor of the protease activator protein 1 receptors on platelets that are activated by thrombin.

Vorapaxar is indicated for the reduction of atherothrombotic events in patients with a history of myocardial infarction or with peripheral arterial disease.

Vorapaxar is classified as a prescription medicine in Australia.

Recommendation

That vorapaxar should be classified 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 2016

a.

Benzodiazepine derivatives

The Australian Delegate has administratively amended the listings of benzodiazepines derivatives under Schedules 2 and 9 (prescription medicine and prohibited substances) of the Therapeutics Good Administration Act 1989.

The Australian Delegate decided that:

1. dicyclazepam, pyrazolam, clonazolam, deschloroetizolam, flubromazepam, nifoxipam and meclonazepam, not previously scheduled, be separately specified as prohibited substances (Schedule 9), and
2. the current scheduling of other benzodiazepines remains appropriate.

In New Zealand, benzodiazepine derivatives are captured under a group entry in Medicines Regulations 1984. Benzodiazepine derivatives are also individually listed under Schedule 3: Class C controlled drugs of the Misuse of Drugs Act as class 5 controlled drugs.

It was proposed to adjust the administrative listing of benzodiazepine derivatives for clarity by maintaining the group listing and also to individually list each benzodiazepine derivative by their classification under the Medicines Act.

Recommendation

That the group classification for benzodiazepine derivatives remains and that each known derivative is also included individually in Schedule 1 of the Medicines Regulations.

b.

Paracetamo

The Australian Delegate considered a proposal to amend its pharmacy only (Schedule 2) entry of paracetamol to:

1. restrict the pack size requirements to no more than 100 tablets or capsules per pack and no more than 50 wrapped powders or sachets of granules per pack for domestic supply, and
2. specifically limit bulk pack sizes of paracetamol for supply only to hospital, nursing homes and pharmacies for dispensing purposes.

Paracetamol is classified as a pharmacy only medicine (Schedules 2), restricted medicine (Schedule 3) and a prescription medicine (Schedule 4) in Australia.

Pharmacy only medicine (Schedule 2)

Paracetamol for therapeutic use:

3. when combined with ibuprofen in preparations for oral use when labelled with a recommended daily dose of 1200 mg or less of ibuprofen in divided doses in a primary pack containing no more than 12 dosage units per pack; or
4. in tablets or capsules enclosed in a primary pack containing not more than 100 tablets or capsules; or
5. in tablets or capsules enclosed in a primary pack containing more than 100 tablets or capsules intended only as a bulk medicine pack and labelled 'For dispensing only' and 'This pack is not to be supplied to a patient'; or
6. in individually wrapped powders or sachets of granules enclosed in a primary pack containing not more than 50 wrapped powders or sachets of granules; or
7. in individually wrapped powders or sachets of granules enclosed in a primary pack containing more than 50 wrapped powders or sachets of granules intended only as a bulk medicine pack and labelled 'For dispensing only' and 'This pack is not to be supplied to a patient'; or
8. in other preparations
   except:
   1. when included in Schedule 3 or 4; or
   2. in individually wrapped powders or sachets of granules each containing 1000 mg or less of paracetamol as the only therapeutically active constituent (other than phenylephrine and/or guaiphenesin or when combined with effervescent agents) when:
      1. enclosed in a primary pack that contains not more than 10 such powders or sachets of granules.
      2. compliant with the requirements of the RASML.
      3. not labelled for the treatment of children 6 years of age or less.
      4. not labelled for the treatment of children under 12 years of age when combined with phenylephrine and/or guaiphenesin; or
   3. in tablets or capsules each containing 500 mg or less of paracetamol as the only therapeutically active constituent (other than phenylephrine and/or guaiphenesin or when combined with effervescent agents) when:
      1. packed in blister or strip packaging or in a container with a child resistant closure.
      2. in a primary pack that contains not more than 20 tablets or capsules.
      3. compliant with the requirements of the RASML.
      4. not labelled for the treatment of children 6 years of age or less.
      5. not labelled for the treatment of children under 12 years of age when combined with phenylephrine and/or guaiphenesin.

Restricted medicine (Schedule 3)

Paracetamol when combined with ibuprofen in a primary pack containing 30 dosage units or less except when included in Schedule 2.

Prescription medicine (Schedule 4)

Paracetamol:

9. when combined with aspirin or salicylamide or any derivative of these substances except when separately specified in the Schedules;
10. when combined with ibuprofen in a primary pack containing more than 30 dosage units;
11. in slow release tablets or capsules containing more than 665 mg paracetamol;
12. in non-slow release tablets or capsules containing more than 500 mg paracetamol;
13. in individually wrapped powders or sachets of granules enclosed in a primary pack containing more than 50 wrapped powders or sachets of granules except when included in Schedule 2; or
14. for injection.

It was proposed to amend the classification of paracetamol in New Zealand to align with the Australian scheduling of paracetamol.

The Committee considered harmonising with the above classification.

Discussion

The Committee reviewed the changes made in Australia. The Committee noted the comment made regarding the complications of limiting pack sizes and that classification cannot be used to limit the number of packs sold in a single purchase. This lead to the discussion of the practice in the UK, where supermarkets limit the sales of paracetamol to two packs per customer. The Committee noted that this practice is self-implemented and that the UK supermarkets are being socially responsible.

The Committee noted that Medsafe considered that a pack size of more than 100 tablets is not considered an over the counter medicine.

The Committee noted that some pharmacies and supermarkets have websites which permit the purchase of general sale medicines and pharmacy only medicines, including paracetamol. The Committee also noted that paracetamol for sale in store or online can be purchased in unlimited quantities. The Committee discussed the possibilities of restricting online sales of paracetamol from pharmacies and supermarkets in New Zealand to limit the number of packs that can be purchased.

Recommendation

That the pharmacy only entry should be amended to a single pack size of a maximum of 100 tablets or capsules.

That no other change should be made to the existing classifications of paracetamol.

That Medsafe should write to the Pharmacy Council and the Food and Grocery Council appraising them that general sale packs of paracetamol should not be sold online by grocery retailers. Pack sizes sold by online pharmacies should be restricted to 32 tablets or capsules and similar oversight should be applied as to in store shopping.

9

Agenda items for the next meeting

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

1. codeine – proposing to reclassify as a restricted medicine
2. final version of proposed update to the document titled ‘How to change the legal classification of a medicine in New Zealand’

10

General business

10.1

Letter from New Zealand Self Medication Industry on the classification of pholcodine

The Committee discussed the letter from New Zealand Self Medication Industry (NZSMI) on the classification of pholcodine. It was noted that pholcodine had been reviewed several times and that the last time the Committee reviewed it was in 2013.

It was considered that no new information was available for review.

The Committee noted paragraph 7 and considered that the interpretation of the data was incorrect and misleading.

A recent study by Katelaris et al has provided new evidence that links pholcodine consumption with antibodies to pholcodine (PHO), morphine (MOR) and suxamethonium. It compared the lgE antibody levels between Australia, a relatively high consumer of pholcodine, with those in Japan and Korea, where pholcodine is not available. Specifically, it found that in Australia 10% were positive to PHO and 8.6% to MOR compared to 0.8% in Japan and 1.0 and 0.5%, respectively, in Korea. Reported anaphylactic reactions to NMBAs are more than 10 times as frequent in Australia than in Japan. These authors concluded that this study supports the pholcodine hypothesis.

The Committee considered that if there was a cause for concern that the appropriate mechanism would be to remove pholcodine from the Medicines Regulations. In which case, Medsafe would need to reassess the risk:benefit profile or determine whether the concerns raised could be mitigated via reclassification.

Recommendation

That the Secretary should write to New Zealand Self Medication Industry informing them that the Committee did not consider there to be sufficient evidence to support a submission for the reclassification of pholcodine.

11

Date of next meeting

The next meeting will be held in May 2017.