Revised: 23 May 2013

Committees

Minutes of the 48th meeting of the Medicines Classification Committee - 30 October 2012

held in the Medsafe Boardroom, level 6, Deloitte House. 10 Brandon Street, Wellington. Commencing at 9:30am

Present:

Dr Stewart Jessamine (Chair)
Dr Melissa Copland
Dr Timothy Healy
Mr Andrew Orange
Dr Mark Peterson
Dr Enver Yousuf
Ms Andrea Kerridge (Secretary)

In Attendance (from Medsafe):

Mrs Marie Prescott (Advisor Science, Medicines Assessment)
Mr Ian Ross (Senior Advisor Science, Medicines Assessment)

Observers (for specific agenda items only)

Aspen Pharma Pty Limited
Bayer Australia Limited
Pharma Projects Limited
Pharmacybrands Limited
Reckitt Benckiser (New Zealand) Limited
Roche Products (New Zealand) Limited
Salterelo Limited

1 WELCOME

The Chair opened the 48^th meeting at 9:30am and welcomed members and guests.

2 APOLOGIES

There were no apologies.

3 CONFIRMATION OF THE MINUTES OF THE 47^TH MEETING HELD ON TUESDAY 1 MAY 2012

The minutes of the 47^th 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.

One member declared a potential conflict with agenda items 5.4 (influenza vaccine) and 6.1 (diphtheria, tetanus and pertussis (acellular, component) vaccine). That member is now on the Board of The Royal New Zealand College of General Practitioners. During the consultation period, the College had provided comment on agenda items 5.2, 5.4 and 6.1. The Committee agreed, because that member was on the Committee as an expert and not a representative of the College, the member could participate fully in discussion.

All 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 47^th meeting

No objections had been received.

5.2 Classification Criteria

At the 47^th meeting a member suggested that revisiting the criteria used when considering a medicine for reclassification for non-prescription sale should be added to the agenda of this meeting. As suggested, the Committee began the process for consideration of the criteria it uses. In opening the discussion, the Chair told members that this consideration would potentially run over a number of meetings and, if any changes to the criteria for reclassification were recommended by the Committee, public consultation on proposed new criteria would be necessary.

The Committee currently uses the following definition, adopted in 1990 by the Commission of the European Communities, for suitability for non-prescription sale:
Medical products which may be available without prescription shall show a substantial safety in use in the treatment of minor ailments or symptoms, usually capable of rapid and spontaneous relief, which are easily identifiable by users and do not justify a medical consultation.

The Committee currently consider the following criteria. The list is not ranked in any order of importance. The criteria can vary in importance according to the medicine being considered for reclassification. In some cases one criterion alone may be sufficient to outweigh all others in determining whether or not a medicine should be reclassified.

Consumer convenience

Accessibility of the medicine and suitability for self-treatment. Accessibility includes time and location factors. Conditions suitable for self-treatment are usually minor and self-limiting.

Potency

The ability of a medicine to produce a wanted pharmacological effect.

Current availability

The availability of products with a similar therapeutic purpose.

Therapeutic index

The margin between therapeutic and toxic effects.

Toxicity

The potential of a substance to produce adverse preclinical and clinical effects. Adverse clinical effects will be assessed by frequency and severity.

Abuse potential

The use of a medicine for gratification-producing effects not required for therapy.

Inappropriate use

Factors relevant to the minor ailment or symptom for which the medicine is indicated, including the suitability of the condition for self-monitoring and the likelihood of misdiagnosis.

Precautions

Factors relevant to the medicine under consideration such as contraindications, side-effects and interactions with other medicines.

Communal harm

The possibility of community harm resulting from wider use of the medicine in question (eg, the development of antibiotic resistance in bacteria).

The Committee also considered the following documentation:

1. Australian Government. 2012. Australian Therapeutic Goods Act 1989. URL: http://www.comlaw.gov.au/Details/C2012C00355 (accessed 26 October 2012).
2. Brass EP, Lofstedt R and Renn O. 2011. Improving the Decision-Making Process for Non-prescription Drugs: A Framework for Benefit-Risk Assessment. Clinical Pharmacology & Therapeutics 90(6): 791-803.
3. Medicines and Healthcare products Regulatory Agency. 2012. Consultation on how to change the legal classification of a medicine in the UK. URL: http://www.mhra.gov.uk/Publications/Consultations/Medicinesconsultations/othermedicinesconsultations/CON172234 (accessed 11 October 2012).
4. Medsafe. 2010. Medicines Classification Committee - Members' Handbook. Wellington: Medsafe.
5. Therapeutic Goods Administration. 2010. National Coordinating Committee on Therapeutic Goods - Scheduling Policy Framework for Medicines and Chemicals. Canberra: Therapeutic Goods Administration.

Two pre-meeting comments had been received during the consultation period:

1. One supported the review of classification criteria. It encouraged the Committee to have an expanded view of which factors to consider during the reclassification process and supported the use of a value-tree tool (Brass et al 2011) as another means of assessing medicines for reclassification.
2. The other expected that the review would not proceed any further without extensive consultation with stakeholders.

One member noted the definition adopted in 1990 by the Commission of the European Communities for suitability for non-prescription sale, and currently used by the Committee, was out of date. The Committee acknowledged that it was time to reconsider the classification criteria currently used and discussed a number of ideas using the documentation presented. Although medicine cost as a consequence of reclassification was not discussed at meetings, other than in terms of consumer convenience, the Committee agreed any future classification criteria should align with what matters to the consumer. It was considered worthy to include discussion of the potential impact of a reclassification on cost during the development of revised criteria.

The Committee noted that at the last meeting it had agreed it would be willing to receive submissions that use the value-tree tool set out in a key paper by Brass et al in 2011.

It was suggested to the Committee that they could consider adopting an approach that is currently under consultation in the United Kingdom whereby companies can request a scientific advice meeting with the Medicines and Healthcare products Regulatory Agency in advance of any reclassification submission. However, it was noted that this would pose a significant resource issue for Medsafe and could be considered a conflict of interest for the Ministry of Health members of the Committee.

Another approach under consultation in the United Kingdom was requesting a risk management and monitoring plan with a reclassification recommendation. European legislation requires that most medicines require a risk management plan to be submitted with an application to market a product. The Committee questioned whether a requirement to have a risk management plan that included safety monitoring, as part of a reclassification application, would improve the chance of reclassification or be seen as a barrier to changing access to a medicine.

It was noted that the results of the consultation in the United Kingdom had yet to be finalised and published. The results of the consultation would be beneficial for the Committee to consider. Also, it was considered important to consider the classification criteria used in Australia to facilitate harmonisation. The Committee agreed it would be useful for Medsafe to put together a paper for discussion that included the outcome of the United Kingdom consultation and options for considering a medicine for reclassification for non-prescription sale.

The Committee also briefly discussed the induction process when a new member joined. Members commented it took a number of meetings to fully understand the classification criteria and how they should be applied to an application for reclassification. One member had observed their first meeting and commented it was really useful to see the Committee in action before fully participating in a meeting.

Recommendation

• That the classification criteria would be considered at the next meeting.
• That Medsafe should put together a paper with the outcome of the United Kingdom consultation and classification criteria options for discussion at the next meeting.

5.3 Bifonazole
(Caneston Once Daily Bifonazole Athlete's Foot and Caneston Once Daily Bifonazole Body, Bayer New Zealand Limited)

At the 46^th meeting on 15 November 2011, the Committee recommended that a number of medicines, used by podiatrists and currently classified as pharmacy-only medicines, should include the wording 'except when sold in practice by a podiatrist registered with the Podiatrists Board'. Bifonazole was not included in these medicines.

Bayer New Zealand Limited made a submission for the reclassification of bifonazole so that the pharmacy-only classification includes the wording 'except when sold in practice by a podiatrist registered with the Podiatrists Board'. The submission proposed the reasoning already applied to these other products was equally valid for bifonazole. Bifonazole is in the same class and has a similar efficacy and safety profile to many of the medicines that have already been made available to podiatrists.

Bifonazole is currently classified as:

• prescription; except for dermal use
• pharmacy-only, for dermal use except in medicines for tinea pedis only or in shampoos containing 1% or less
• general sale; for dermal use in medicines for tinea pedis only or in shampoos containing 1% or less.

The Committee noted there were two products currently marketed in New Zealand that could be affected by a reclassification to include sale by a podiatrist. The Committee also noted that in Australia the Delegate had decided not to harmonise with this reclassification. The reclassification was not possible at the present time in Australia because of the way the definitions of medical practitioners are described within the Standard for the Uniform Scheduling of Medicines and Poisons (ie, medical practitioners are not specifically mentioned within the Schedules).

One comment was received during the consultation period. It suggested that the Committee also consider including Canesten Plus (clotrimazole 10 mg/g and hydrocortisone 10 mg/g) topical cream to be made available for podiatrists. This would require a reclassification of hydrocortisone so that the pharmacy-only classification included the wording 'except when sold in practice by a podiatrist registered with the Podiatrists Board'. Clotrimazole had been included in the list of medicines used by podiatrists and had been reclassified following the 46^th meeting. The interested party argued that it would be advantageous to New Zealand consumers if podiatrists could supply this efficacious medicine.

The Committee noted that, although the reclassification request was simply changing who could sell the product, no supporting data had accompanied the submission. It was queried as to why a product intended for use on various parts of the body (Canesten Plus) was included in the submission when the reclassification would allow the product only to be sold by a podiatrist. As a data sheet was not included it was unclear what Canesten Plus was indicated for. It was also queried as to why Podiatry New Zealand had not included bifonazole in their submission to the 46^th meeting.

The Committee agreed there was not enough data included with the submission to make a recommendation on the reclassification of bifonazole, or clotrimazole / hydrocortisone in this context. However, a submission with supporting data which answered the queries discussed would be considered at a future meeting if submitted.

Recommendation

That a revised submission to reclassify bifonazole, so that the pharmacy-only classification includes the wording 'except when sold in practice by a podiatrist registered with the Podiatrists Board', would be considered at a future meeting if submitted.

5.4 Influenza vaccine
(Pharmacybrands Limited)

At the 47th meeting, the Committee recommended that 'influenza vaccine should be reclassified from prescription medicine to prescription medicine except when administered to an adult by a pharmacist who has successfully completed the New Zealand Qualifications Authority approved vaccinator's training course and is complying with the immunisation standards of the Ministry of Health'.

On 12 July 2012 the classification of influenza vaccine was gazetted as a prescription medicine; except when administered to an adult in a pharmacy by a registered pharmacist who has successfully completed the New Zealand Qualifications Authority approved vaccinator training course and is complying with the immunisation standards of the Ministry of Health.

Following the gazette notice, Pharmacybrands Limited requested that the classification wording for the influenza vaccine be reviewed to clarify the adult age (to '18 years of age or over'), to consider whether the words 'in a pharmacy' are necessary and to reword the provider requirements for the vaccinator course (to 'has successfully completed the Immunisation Advisory Centre vaccinator training course').

The Committee considered this request. The main concern was the removal of the words 'in a pharmacy'. Although the words 'in a pharmacy' were not included in the original application to the Committee and were not a specific recommendation, the Committee's discussion at the last meeting centred on having the vaccination in the clinical setting of a pharmacy. Vaccinations carried out by pharmacists in workplaces or other environments were not considered. The Chair asked the Committee to consider whether it would be appropriate for pharmacists to administer the vaccination in a pharmacy for a specific amount of time following the recent reclassification, before considering changing the classification statement to allow pharmacists to give the vaccination in workplaces and other environments.

The Chair also clarified the reclassification of influenza vaccine. The reclassification means that pharmacists will need to complete a defined training course to become vaccinators. However, unlike most vaccinations, the vaccination programme administered within their pharmacy practice does not need Medical Officer of Health's approval or oversight because the vaccine is not a prescription medicine when administered by a pharmacist.

Pharmacybrands Limited provided the Committee with a copy of their Standard Operating Procedure for influenza vaccine administration in a non-clinical setting (version 8, 28 August 2012). In a letter to the Chair dated 27 September 2012, Pharmacybrands Limited also highlighted that:

1. to date no adverse events or safety concerns have been raised by either the consumer or pharmacist for influenza vaccines administered outside the pharmacy environment
2. safety concerns of influenza vaccination are managed within the pharmacy and off-site on the same way
3. within New Zealand vaccination training is not specific to the environment of administration but focuses on safe delivery through the following of process and attention to cold chain integrity
4. the effect of limiting the classification status to 'in a pharmacy' would be to restrict pharmacists in their ability to reach New Zealanders.

The Committee also considered Chapter 2 of the Immunisation Handbook 2011, Processes for Safe Immunisation.

Three pre-meeting comments were received during the consultation period. One strongly urged the Committee to carefully evaluate how the existing scheme works in practice before removing the requirement to administer the vaccine in a pharmacy. The other two supported the rewording of the classification statement.

All Committee members agreed that the adult age should be clarified to '18 years of age or over'.

The Committee acknowledged that the training required was sufficient for a pharmacist to administer a vaccination safely whether it was in a pharmacy or in the community. Following training a pharmacist would be considered the same as any other accredited vaccinator. It was the responsibility of the vaccinator to have the correct emergency equipment with them either in a pharmacy or in the community. Fragmentation of care had been discussed at the last meeting and was not seen as a big enough risk to prevent the reclassification. Following discussion the Committee agreed that the words 'in a pharmacy' should be removed from the classification statement.

One member suggested that, rather than rewording the provider requirements for the vaccinator course to 'has successfully completed the Immunisation Advisory Centre vaccinator training course', it would be preferable to keep the requirements generic and not specify a particular provider. The Committee agreed that wording similar to 'has successfully completed a vaccinator training course approved by the Ministry of Health' would be preferable.

One member expressed their concern over the level of resuscitation training required by certified vaccinators. The level required was the New Zealand Resuscitation Council's Level 3, which included administration of adrenaline in anaphylaxis. However, it was noted that Level 3 training may not cover enough material to enable someone to resuscitate a collapsed patient. The concern over training would affect all certified vaccinators and not just pharmacists. It was acknowledged that it was not in the Committee's remit to discuss training requirements for vaccinators. However, the Chair agreed the concern over training should be noted and that it would be appropriate to write to the Ministry to Health explaining the concern.

The Committee concluded that the classification statement for the influenza vaccine should be reworded as requested, except for specifying the training provider of the training course.

Recommendation

• That the classification statement for influenza vaccine be changed to clarify the adult age (to '18 years of age or over'), to remove the words 'in a pharmacy' and to reword the provider requirements for the vaccinator course (to 'has successfully completed a vaccinator training course approved by the Ministry of Health').
• That the Chair should write to the Ministry of Health regarding concerns over the level of resuscitation training required by certified vaccinators.

6 SUBMISSIONS FOR RECLASSIFICATION

6.1 Diphtheria, tetanus and pertussis (acellular, component) vaccine
(Pharmacybrands Limited)

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

Purpose

This was a submission from Pharmacybrands Limited (the parent company for Life, Unichem, Amcal, Radius and Care Chemist pharmacies in New Zealand) for the reclassification of diphtheria, tetanus and pertussis (acellular, component) vaccine (Tdap) in a single dose from prescription medicine to prescription medicine except when administered to a person aged 16 years or over by a pharmacist who has successfully completed the Immunisation Advisory Centre vaccinator course and is complying with the immunisation standards of the Ministry of Health.

The submission suggested any vaccination currently marketed containing tetanus, diphtheria or pertussis antigens would be affected by the proposed reclassification. However, given that the submission suggests administration to a person aged 16 years or over, the primary vaccination (DTaP) is not proposed to be administered by a pharmacist. The Committee noted there were eight products currently marketed that would be affected.

Background

At the 7^th meeting on 31 July and 1 August 1990, the Committee recommended that diphtheria toxoid be classified as a prescription medicine, and confirmed that tetanus antitoxin and tetanus toxoid be classified as a prescription medicines.

At the 21^st meeting on 25 March 1999, the Committee recommended that pertussis antigen be classified as a prescription medicine.

All vaccines are currently classified as prescription, except when specified elsewhere in the Schedule.

Comments

A letter of support was received from a Paediatrician in Auckland who reviewed the submission in advance of the meeting and had made several suggestions on the draft materials. The suggestions included:

1. reducing the age of immunisation down to 16 years of age and over
2. immunising women from week 20 of their pregnancy without referral to their doctor or lead maternity carer
3. contacting the lead maternity carer in advance of the immunisation was not necessary and could cause a delay
4. not restricting the vaccination to people currently in close contact with infants only.

An additional eight pre-meeting comments were received during the consultation period. Two of the eight comments were received late.

Four of the pre-meeting comments supported the reclassification for the following reasons:

1. anything that can be done to increase the level of vaccinations in New Zealand should be supported
2. whooping cough outbreaks are a serious public health issue
3. it is essential to increase the number of approved vaccinators who can administer whooping cough vaccines in the community
4. if pharmacists are able to vaccinate the adults in a family, through 'cocooning' it will help to protect vulnerable babies and young children
5. community pharmacies are a convenient place for a vaccination
6. community pharmacists providing influenza vaccines have shown they work closely with general practice, keeping them informed of vaccinations and any other health concerns
7. pharmacists, who have completed the same training requirements as all other authorised vaccinators, should be able to administer this important vaccine
8. it would provide another mechanism by which to manage the current pertussis outbreak.

A comment from the Immunisation Team in the Ministry of Health proposed lifting the age to 18 years or older. This age limit would align with the age for the influenza reclassification and also with the Ministry's eligibility criteria which provides free National Immunisation Schedule vaccines to children up to their eighteenth birthday. This age limit would also create much less confusion for health professionals and consumers. The Immunisation Team also suggested that pharmacists should notify general practitioners when the vaccine is given.

Four of the pre-meeting comments did not support the reclassification because of the following factors:

1. general practitioners make no profit from their prescription recommendations
2. the reclassification would lead to further fragmentation of medical treatment and care
3. patients may miss out on other services provided around immunisations (eg, checking they are taking prescribed medications, other vaccinations, cervical screening, mammography, blood pressure checks, skin checks, cardiovascular risk assessment, etc.).
4. pharmacies are not staffed or equipped to deal with serious reactions
5. a pharmacist's training and qualifications do not provide them with the clinical experience to safely administer an intra-muscular injection
6. tetanus containing vaccines are the most likely vaccine to cause a patient to faint - the vaccinator needs to have worked in a clinical setting where they have experienced faints, know how to prevent them, manage them and easily recognise a faint from an anaphylactic reaction
7. community pharmacists do not have the refrigerated storage capacity or the facilities to be involved in an outbreak vaccination program
8. a written protocol for prescribing is not sufficient to enable pharmacists to appropriately prescribe vaccines
9. it seems wrong to allow pharmacists who are not qualified or experienced to be able to give a vaccine, when nurses who are qualified and experienced in vaccinating under the standing orders of their local office of health or medical practitioner cannot.

Discussion

Pharmacists giving vaccinations was not considered an issue because the precedent had already been set with the reclassification of influenza vaccine at the last meeting. However, there were practical differences between Tdap and the influenza vaccine which raised a number of questions that were not answered in the submission.

It was unclear how much training would be required to give the intramuscular injection required for Tdap. The Immunisation Advisory Centre vaccinator course is aimed at nurses who have already received training in injection technique whereas pharmacists may have not. The observers confirmed that many pharmacists have already been taught how to inject. It was noted that the approved vaccinator training that pharmacists were required to undertake was no different from that for other approved vaccinators.

Who should be given booster doses of Tdap and how would pharmacists identify them? Pharmacists would ideally need access to the National Immunisation Register. The observers stated that signs would be put up in pharmacies. It would be easy to identify those with babies or women who were pregnant, and those buying pre-pregnancy tests from the pharmacy. Family Health Diary had recently advertised the need for Tdap booster immunisation. Pharmacists would identify those who required vaccinating opportunistically. The observers also confirmed that Tdap is not a funded vaccine so would not be included on the National Immunisation Register.

How often should Tdap be given? Why was a five year cut off point chosen when a booster is recommended every 10 years? The observers confirmed that the references provided with the submission suggested the vaccination waned after five years, hence the five year point was chosen. Advice from the Immunisation Advisory Centre states repeat pertussis vaccination can be given at any time.

How would pharmacists deal with any adverse effects? A high number of reactions have been recorded with the tetanus vaccination which would need to be included in the information for pharmacists. It was agreed that it was essential for a general practitioner to be informed that their patient had received Tdap. The requirement for a patient to remain observed on site for 20 minutes would also minimise some of the risk to the patient.

Why did the submission concentrate only on pertussis when the proposal to reclassify included tetanus and diphtheria? The submission should have concentrated on all three vaccinations equally. The Committee expressed a concern that patients would not register they were receiving the other vaccinations. Research data on multiple dosing and increased reactions was not available for each of the three components of the vaccine. The observers confirmed that pertussis was the primary objective of the reclassification submission because of the current epidemic. Tdap would present an additional opportunity to administer a booster for tetanus and diphtheria. If a patient did not remember having the other vaccinations then the default would always be to refer them back to their general practitioner. However, it was disputed as to whether a general practitioner would have vaccination details of all patients.

The Committee discussed the safety of tetanus and diphtheria although data was not provided with the submission. There are few safety issues with repeat vaccination. There is international evidence that supports the safety and efficacy of Tdap. The Food and Drug Administration and the American Medical Association endorse the delivery of the vaccine via pharmacy. It was noted that the submission did not include information that detailed how suitability for booster immunisation was assessed and how pharmacists manage the vaccine in overseas markets where pharmacists administer booster doses of the primary vaccination (DTaP), only that the programme was successful.

If a patient has not received the primary vaccination (DTaP), would the booster vaccination give full immunity? There was a specific cohort of patients who did not receive the primary vaccination in New Zealand so it is not clear whether they would they benefit from a booster, or have a suboptimal immune response to the immunisation with the potential for vaccine failure. The Immunisation Advisory Centre recommends vaccinating adults against pertussis using Tdap. It was noted that the influenza vaccine and Tdap can be given at the same time.

The comments made by one member in item 6.1, regarding keeping the training requirements generic and not specify a particular provider, were also relevant to the submission. The Committee restated that wording similar to 'has successfully completed a vaccinator training course approved by the Ministry of Health' would be preferable.

The same member (as in item 5.4) expressed their concern over the level of resuscitation training required by certified vaccinators. The level required was the New Zealand Resuscitation Council's Level 3, which included administration of adrenaline in anaphylaxis. However, it was noted that Level 3 training may not cover enough material to enable someone to resuscitate a collapsed patient. The concern over training would affect all certified vaccinators and not just pharmacists. It was acknowledged that it was not in the Committee's remit to discuss training requirements for vaccinators. However, again the Chair agreed the concern over training should be noted and that it would be appropriate to write to the Ministry to Health explaining the concern.

The observers agreed that if any additional work was required they would seek out expert advice, from the Paediatrician in Auckland and the Immunisation Advisory Centre, and put this advice into the materials for pharmacists.

The Chair summarised the main issue for the Committee. Using Tdap was already routine in other jurisdictions so the Committee should focus on how the vaccination can fit into the New Zealand environment rather than focussing on safety concerns. It was agreed that the public health advantage for reclassifying diphtheria, tetanus and pertussis was well recognised. However, it was essential to both identify the correct population for the booster vaccination and to confirm that the primary vaccination (DTaP) had been given. A patient should be referred back to their general practitioner if the primary vaccination had not been received.

It was concluded that the potential public health benefits were significant and there was low risk of harm. It was considered that diphtheria, tetanus and pertussis (acellular, component) vaccine (Tdap) in a single dose is appropriate for reclassification. However, the Committee agreed that a revised submission for reclassification should be submitted. The revised material should specifically include:

1. data on tetanus and diphtheria
2. detailed information on patient selection
3. information on how to find out if a patient had received the primary vaccination (DTaP).

Recommendation

• That a revised submission to reclassify diphtheria, tetanus and pertussis (acellular, component) vaccine (Tdap), in a single dose from prescription medicine to prescription medicine except when administered to a person aged 18 years or over by a pharmacist who has successfully completed the Immunisation Advisory Centre vaccinator course and is complying with the immunisation standards of the Ministry of Health, would be considered at a future meeting if submitted.
• That the Chair should write to the Ministry of Health regarding concerns over the level of resuscitation training required by certified vaccinators.

6.2 Hydrocortisone topical preparations
(Caneston Plus, Bayer New Zealand Limited)

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

Purpose

This was a company submission from Bayer New Zealand Limited for the reclassification of hydrocortisone from restricted medicine to pharmacy-only medicine when for dermal use in medicines containing 1% or less by weight of hydrocortisone base in combination with an antifungal and in a quantity of 30 g or less or 30 mL or less per container.

The Committee noted there were four products currently marketed in New Zealand that would be affected by the proposed reclassification.

Background

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

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

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

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

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

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

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

• prescription; except when specified elsewhere in the Schedule
• restricted; for dermal use in medicines containing 1% or less but more than 0.5% by weight of hydrocortisone base with no other active ingredient except an antifungal and in a quantity of 30 g or less or 30 ml or less per container; in rectal medicines containing 1% or less but more than 0.5% by weight of hydrocortisone base and in combination with a local anaesthetic and in a quantity of 35 g or less per container or up to 12 suppositories per pack
• pharmacy-only; for dermal use in medicines containing 0.5% or less by weight of hydrocortisone base with no other active ingredient except an antifungal and in a quantity of 30 g or less or 30 ml or less per container; in rectal medicines containing 0.5% or less by weight of hydrocortisone base and in combination with a local anaesthetic and in a quantity of 35 g or less per container or 12 suppositories or fewer per pack.

Comments

Two pre-meeting comments were received during the consultation period. These comments did not support the proposed reclassification for the following reasons:

• pharmacists regularly have to explain hydrocortisone's purpose
• long term steroid use will mask the symptoms of an infection when it is not improving
• patients will soon learn that hydrocortisone is available in combination form and will purchase this to treat dermatitis even when an antifungal is not warranted
• careful questioning and counselling involving a pharmacist must occur to ensure that the product is being used appropriately and not for prolonged periods without medical review.

Discussion

The observers confirmed the same submission for reclassification had been submitted in Australia and would be considered in March 2013.

The Committee expressed concern that medicines containing 1% or less of hydrocortisone could have adverse effects if used inappropriately. There was no evidence included with the submission that combining hydrocortisone with an antifungal decreases the amount of absorption or improves its safety profile. Hydrocortisone can cause skin thinning when used. Although a patient recovers quickly after the use of hydrocortisone has stopped, this adverse effect could be caused inadvertently by prolonged use.

There was a concern over the long term use of medicines containing 1% or less of hydrocortisone. Patients may not use the medicine for the seven days as directed on the packaging. If used for too short or long a period the medicine may be ineffective or there may be adverse effects. There was also an issue of sub-optimal treatment with multiple short interval treatments occurring as patients stopped treatment when they received symptom relief. When prescribed in general practice hydrocortisone is often prescribed with another medicine.

The Committee also expressed a concern with the indication for use in Candida nappy rash. One of the current warnings on the pack, 'do not use on children under 2 years unless your doctor tells you to', would not be appropriate for a pharmacy-only pack. It was felt that a parent or caregiver would not be able to make a diagnosis of fungally infected nappy rash. If this was misdiagnosed there were potentially severe consequences.

The Consumer Medicine Information included with the submission was for the restricted classification. The Committee commented it would have been preferable to have seen the Consumer Medicine Information proposed for the pharmacy-only classification, with appropriate warnings for self-selection, included with the submission.

The advantages of having a pharmacy-only classification were questioned. The observers confirmed the medicine may be appropriate for down-scheduling as evidenced by overseas experience. However, one member suggested it was important to note that the references included with the submission did not actually demonstrate that there was much evidence of use overseas - the main review looked at products containing 5% and 2.5% hydrocortisone, there was a retrospective telephone survey and a review by the Food and Drug Administration which had the limitations of such a survey technique.

The observers stated there was already a similar product in use in Australia at the pharmacy-only level. They had carried out a search of any adverse effects with this product at the pharmacy-only level and there were no arising issues. The observers confirmed they had tried to stay within the current labelling guidelines and the nappy rash indication had been kept as the status quo.

The observers highlighted one of the references included with the submission concluded that the data suggested over-the-counter hydrocortisone products are used for self-treatment in a limited and appropriate fashion that is likely to be safe in both adults and children. This study was carried out in the United States and there was no reason to believe that New Zealanders would behave differently.

The Committee discussed the option of removing the nappy rash indication for a pharmacy-only classification. The observers confirmed they had worked with dermatologists in writing the submission, particularly with the nappy rash indication. It was concluded that the current warning 'do not use on children under 2 years unless your doctor tells you to' was still the best advice for parents. The warnings were consistent with the Food and Drug Administration's advice in the United States.

The Committee concluded that hydrocortisone should not be reclassified from restricted medicine to pharmacy-only medicine when for dermal use in medicines containing 1% or less by weight of hydrocortisone base in combination with an antifungal and in a quantity of 30 g or less or 30 mL or less per container. The reasons for the recommendation were concerns with:

1. the nappy rash indication
2. prolonged use
3. safety and efficacy of hydrocortisone when in presented as a fixed dose combination with an antifungal agent.

Recommendation

That hydrocortisone should not be reclassified from restricted medicine to pharmacy-only medicine when for dermal use in medicines containing 1% or less by weight of hydrocortisone base in combination with an antifungal and in a quantity of 30 g or less or 30 mL or less per container.

6.3 Ibuprofen in liquid sachet unit dose forms
(Reckitt Benckiser (New Zealand) Limited)

One representative of the company observed the discussion but left the meeting room before a final recommendation was made.

Purpose

This was a company submission from Reckitt Benckiser (New Zealand) Limited for the reclassification of ibuprofen, when in liquid oral suspension in sachets each containing 200 mg or less of ibuprofen for use in adults or children 12 years of age and older, from pharmacy-only medicine to general sale medicine.

The Committee noted there were no products, containing ibuprofen in liquid oral suspension in sachets for use in adults or children 12 years of age and over, currently marketed in New Zealand that would be affected by the proposed reclassification.

Background

At the 7^th meeting on 31 July and 1 August 1990, the Committee decided that a recommendation to change the classification of liquid ibuprofen could not be made on the basis of the limited information available.

At the 13^th meeting on 26 May 1994, the Committee recommended that ibuprofen syrup be available as a restricted medicine when for children over 12 months of age. Also, in addition to the warnings suggested by the company, the labels should include warnings against use in children with dehydration, diarrhoea or any known gastric problem.

Following the 13^th meeting Committee members were consulted by telephone and agreed that a wider overview should be taken of liquid ibuprofen.

At the 14^th meeting on 2 November 1994, the Committee recommended that ibuprofen in liquid form be classified as a restricted medicine when:

1. sold in the manufacturer's original pack which has the consent of the Minister for sale as a restricted medicine
2. in pack sizes of not more than 200 ml
3. in strengths of 100 mg or less per 5 ml
4. contraindicated for use for children under 12 months of age
5. contraindicated for use in children with a temperature higher than 37.7 degrees centigrade
6. contraindicated for use in children suffering dehydration through diarrhoea and / or vomiting
7. juvenile rheumatoid arthritis is not included as an indication.

In a postal consultation conducted in May 1995, the Committee recommended that the temperature contraindication be removed for the sale of liquid ibuprofen as a restricted medicine.

At the 19^th meeting on 19 May 1998, the Committee recommended that ibuprofen should be a pharmacy-only medicine when in liquid form for oral use in medicines sold in the manufacturer's original pack containing 200 ml or less in volume and in strengths of 100 mg or less per 5 ml and when bearing the package information required in the New Zealand Regulatory Guidelines for the medicines to be sold over-the-counter.

At the 27^th meeting on 23 May 2002, the Committee recommended that:

1. the maximum daily dose for pharmacy-only solid dose and liquid ibuprofen should not exceed 1200 mg
2. the maximum pack size for pharmacy-only liquid preparations should not exceed 4 g of total ibuprofen content
3. packs for pharmacy-only sale should be in concentrations only of 100 mg in 5 ml or 200 mg in 5 ml of ibuprofen
4. the changes should be notified in the Gazette but Medsafe should be asked to include these changes and other requirements in the Regulatory Guidelines so that they would no longer be required to be listed in amendments to the Schedule
5. the Australian National Drugs and Poisons Schedule Committee be asked to adopt the Committee's recommendation limiting the concentrations of liquid ibuprofen permitted in Schedule 2 (pharmacy-only medicines).

At the 29^th meeting on 22 May 2003, the Committee noted that the Australian National Drugs and Poisons Schedule Committee had opted not to adopt their recommendation. There were no restrictions on the concentration for over-the-counter sale in Australia.

At the 46^th meeting on 15 November 2011, the Committee recommended that New Zealand should harmonise with Australia and increase the maximum allowable amount of ibuprofen in liquid preparations as a pharmacy-only medicine from 4 g to 8 g.

Ibuprofen is currently classified as:

1. prescription; except when specified elsewhere in the Schedule
2. restricted; for oral use in tablets or capsules containing up to 400 mg per dose form and in packs containing not more than 50 dose units and that have received the consent of the Minister or the Director-General to their distribution as restricted medicines and that are sold in the manufacturer's original pack labelled for use by adults and children over 12 years of age
3. pharmacy-only; for oral use in liquid form with a recommended daily dose of not more than 1.2 g for the relief of pain and reduction of fever or inflammation when sold in the manufacturer's original pack containing not more than 8 g; for oral use in solid dose form containing not more than 200 mg per dose form and with a recommended daily dose of not more than 1.2 g when sold in the manufacturer's original pack containing not more than 100 dose units; except in divided solid dosage forms for oral use containing 200 mg or less per dose form with a recommended daily dose of not more than 1.2 g and when sold in the manufacturer's original pack containing not more than 25 dose units
4. general sale; for external use; in divided solid dosage forms for oral use containing 200 mg or less per dose form with a recommended daily dose of not more than 1.2 g and when sold in the manufacturer's original pack containing not more than 25 dose units per pack

Comments

Two pre-meeting comments were received during the consultation period. These comments did not support the reclassification proposal for the following reasons:

1. there would be no public benefit to widened ibuprofen use and significant risk of public harm
2. having both paracetamol and ibuprofen liquids available will lead to the public considering them to be interchangeable as they already do so with the solid dose form - this could easily lead to confusion about the differing doses of ibuprofen compared with paracetamol, resulting in ibuprofen overdose
3. if ibuprofen is supplied in sachet form, there will be a tendency for parents to use the rest of the sachet if the recommended dose is part of the sachet
4. side effects of ibuprofen are significant (eg, gastrointestinal upset, asthma, allergy and ophthalmic effects)
5. having any kind of age restriction on a general sale medicine is completely meaningless when the purchase and intent of use of that medicine is not monitored.

Discussion

Ibuprofen is already available in divided solid dosage forms for oral use containing 200 mg or less per dose form at a general sale classification. The issue the Committee considered was the formulation (ie, liquid oral suspension in sachets). Although liquid ibuprofen is usually a formulation used with children, the submission targeted adults and children 12 years of age and older who struggled to swallow tablets.

The main concern for the Committee was the potential for off label use in children under 12 years of age because of the risk of overdose. Although the management of ibuprofen overdose is usually conservative, the proposed reclassification would result in a product being marketed to adults that was usually targeted at children which could lead to confusion.

The submission included 5 mL and 10 mL sachets. Some members felt that if both sachet sizes were on the market then this would further confuse parents.

The pack size proposed in the submission was up to 25 dosage units. The Committee discussed minimising the number of dosage units in a pack to reduce the risk.

The Committee discussed whether there would be any benefit for consumers. An oro-dispersible form of ibuprofen is currently available in New Zealand. Most ibuprofen tablets are coated and relatively easy to swallow and it was questioned whether a liquid sachet would offer any more convenience for consumers. The reference provided with the submission that concluded 40% of American adults report experiencing difficulty swallowing pills was published in 2004 and was not felt to be reflective of modern formulations of tablets.

The observer confirmed the sachets would be labelled and packaged similarly to the current general sale tablets. However, one member noted that the current warning statements did not focus on the age group that would be at risk.

Overall, the Committee agreed that safety and efficacy was well defined. It was noted the reclassification would harmonise New Zealand with Australia and other jurisdictions.

The Committee could not reach a consensus on a recommendation. Following discussion, the Committee agreed that a submission to reclassify ibuprofen, when in liquid oral suspension in sachets each containing 200 mg or less of ibuprofen for use in adults or children 12 years of age and older, from pharmacy-only medicine to general sale medicine would be reconsidered at a future meeting if submitted. A revised submission would be required which would need to:

1. include clarification on the dose regime
2. contain specific labelling to minimise the risk of misuse in children
3. address consumer convenience and benefit of wider availability.

Recommendation

That a submission to reclassify ibuprofen, when in liquid oral suspension in sachets each containing 200 mg or less of ibuprofen for use in adults or children 12 years of age and older, from pharmacy-only medicine to general sale medicine would be reconsidered at a future meeting if submitted.

6.4 Melatonin 2 mg prolonged release tablet
(Circadin, Aspen Pharma Pty Limited c/o Pharmacy Retailing (NZ) Limited trading as Health Care Logistics)

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

Purpose

This was a company submission for the reclassification of melatonin 2 mg prolonged release tablets from prescription medicine to restricted medicine, in a pack of up to 30 tablets, when used as monotherapy for the short term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 and over.

The submission proposed to send training material, reviewed by the Pharmaceutical Society of New Zealand and the Pharmacy Guild of New Zealand, to all community pharmacies after reclassification. Also included was an overview of the changes made to the submission at the 47^th meeting on 1 May 2012. Comments and questions raised by the Committee at the 47^th meeting were addressed.

The Committee noted that Circadin was the only product currently marketed in New Zealand that would be affected by the proposed reclassification.

Background

Melatonin was classified urgently as a prescription medicine at the 16^th meeting on 24 April 1996. Before classification a number of supplements had appeared on the New Zealand market bearing therapeutic claims. Melatonin was classified because it is a hormone and at the time there was insufficient data available regarding its effects and safety profile.

At the 47^th meeting on 1 May 2012 the Committee recommended that a revised submission to reclassify melatonin 2 mg prolonged release tablets from prescription medicine to restricted medicine, in a pack of up to 30 tablets, when used as monotherapy for the short term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 and over, would be considered at a future meeting.

Melatonin is currently classified as a prescription medicine.

Comments

Two pre-meeting comments were received during the consultation period. These comments supported the reclassification proposal for the following reasons:

1. melatonin, accompanied by appropriate written instructions on the packaging, is believed to be an appropriate medicine for reclassification to restricted medicine in New Zealand
2. prolonged release melatonin may be a preferable treatment for insomnia compared to prescription hypnotics or sedating antihistamines
3. pharmacists are experienced at refusing sales when the patient does not meet the set criteria for using a medicine
4. pharmacies are regulated regarding keeping accurate records of restricted medicine sales
5. community pharmacists already offer a wide range of personal and public health services (eg, emergency contraception consultations, smoking cessation advice)
6. it is already common for pharmacists to provide advice about insomnia
7. having a wider range of effective products available in a pharmacy increases the chances of patients coming to a pharmacy and therefore increases the chances of patients being referred to another health professional for other health concerns (eg, depression, chronic pain)
8. melatonin has a documented safety profile
9. melatonin is used extensively in the United States as a dietary supplement.

Discussion

The supporting documentation and references provided with the submission referred to 13 week use of melatonin whereas the submission for reclassification was for a pack up to 30 tablets. It would have been preferable for the supporting documentation and references to provide evidence to support 30 days' supply.

Although the potential for adverse effects could be dealt with by labelling, concerns remained over the

1. risk of use in children
2. difficulty in diagnosing primary insomnia correctly, particularly in the elderly
3. likelihood and impact of an important diagnosis being missed.

The observers acknowledged the risk of harm with the reclassification proposal. However, the pharmacists' screening tool included with the submission had been developed with sleep experts from the University of Auckland. The screening tool screens for depression and a patient would be referred to their general practitioner if they exhibited signs of depression. The observers confirmed the algorithm took a pharmacist through a lot of options before reaching a diagnosis of primary insomnia, and through the algorithm many patients would be referred back to their general practitioner.

One of the references provided with the submission was a meta-analysis published in 2005 of the safety and efficacy of exogenous melatonin for primary sleep disorders. The Committee raised concerns that this review was conducted seven years ago so did not include any recent data. The review also did not include data on the safety and efficacy of prolonged release tablets. The observers confirmed that studies on prolonged release tablets were published after the meta-analysis was carried out.

The Committee made a number of suggestions to improve the draft training material for pharmacists provided with the submission. A sleep diary could be included as referred to in one of the references provided. The training material should be linked to the screening tool and algorithm so that they fit together. A normal sleep pattern, and how this differs in patients and at different ages, could be included with the material. It is often useful for a patient's partner to be present when discussing a patient's sleep pattern as they often have a lot of important knowledge. It would be useful to include figures on how many people who can't sleep actually suffer from insomnia.

A new Periodic Safety Update Report (Number 7) was included with the submission which referenced several adverse effects not previously reported. In addition, the Committee noted that new information on adverse effects had been added to the latest European summary of product characteristics provided for prolonged release melatonin. While the Committee recognised the total population of patients prescribed prolonged release melatonin was slowly increasing, it was of the opinion that the safety profile of this medicine was still being defined. A substantial increase in the treated population would be required before the Committee could be comfortable that the adverse event profile for the medicine was stable and the reports of events, such as anxiety disorders and depression, were not significant.

Although melatonin had been used extensively in the United States, the experience had not been with a prolonged release formulation. So although that data was relevant it was not directly applicable to the submission for reclassification.

The Committee agreed that if the indication proposed with the submission was less significant, the recommendation to reclassify to restricted medicine would be more likely. The observers suggested that at the restricted level of reclassification at least a patient would receive guidance from a health professional which would result in better triage for patients. However, it was noted that even general practitioners may struggle diagnosing primary insomnia and there were concerns over whether it was even possible to spend the amount of time needed diagnose it in a pharmacy.

The Committee acknowledged that the submission had resolved some of the issues raised at the last meeting. However, work was still needed on the training material for pharmacists because it did not answer the concerns raised over use in children, the difficulty in diagnosing primary insomnia correctly and the likelihood of an important diagnosis being missed. Signals from the safety data presented were more apparent compared to the submission at the last meeting and more time was needed to observe any effects with this indication.

The Committee agreed that melatonin, in 2 mg prolonged release tablets when used as monotherapy for the short term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 and over, was not ready for over-the-counter sale yet. Patients could still be prescribed the medicine by their general practitioners. More time on the market with experience in New Zealand with the proposed indication was required to reassure the Committee on safety and appropriate use.

Recommendation

That melatonin 2 mg prolonged release tablets should not be reclassified from prescription medicine to restricted medicine, in a pack of up to 30 tablets, when used as monotherapy for the short term treatment of primary insomnia characterised by poor quality of sleep in patients who are aged 55 and over.

6.5 Oseltamivir 75 mg powder filled capsules
(Tamiflu, Roche Products (New Zealand) Limited)

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

Purpose

This was a company submission for the reclassification of oseltamivir in 75 mg powder filled capsules (Tamiflu) from prescription medicine to restricted medicine, in a pack of up to 10 capsules, for the treatment or prophylaxis of influenza in adults and children aged 13 years and older.

The Committee noted that Tamiflu was the only product currently marketed in New Zealand that would be affected by the proposed reclassification.

Background

At the 32^nd meeting on 25 November 2004, the Committee recommended, following a proposal from a Committee member, that oseltamivir be added to the agenda of the next meeting.

At the 33^rd meeting on 9 June 2005, the Committee recommended that, following a company submission, the reclassification of oseltamivir from prescription to restricted medicine should be deferred pending further information regarding resistance, monitoring of resistance, promotion, national strategy and limitation of use.

At the 34^th meeting on 9 June 2006, after considering this further information, the Committee recommended that pharmacists should be able to sell oseltamivir between the months of May and September for the treatment of influenza but not for prophylaxis.

At the 36^th meeting on 8 February 2007, the Committee recommended that oseltamivir should be returned to the agenda after there had been a period of market experience at the new level of access.

At the 39^th meeting on 25 June 2008, the Committee recommended that, following a company submission, there be no change to the current classification of oseltamivir.

At the 40^th meeting on 25 November 2008, the Committee concluded there was no new data from the 2008 influenza season which would justify a change to the current classification of oseltamivir.

At the 41^st meeting on 14 May 2009, the Committee concluded there was insufficient evidence of resistance with exposure to Tamiflu (compared to resistance associated with spontaneous mutations) that would cause them to reconsider the current classification status of oseltamivir.

In response to the pandemic in 2009, on 9 July 2009 the classification of oseltamivir was gazetted as a prescription medicine; except when sold in a pharmacy between the months of May to September inclusive, or for the duration of the Influenza A (H1N1) Pandemic, by a registered pharmacist who is satisfied that the medicine is for the treatment of a consumer who is resident in New Zealand, is 12 years of age or more, and currently has symptoms of influenza; except when supplied from a Community-based Assessment Centre established and operated by a district health board in accordance with a protocol approved by the National Incident Controller for the Influenza A (H1N1) Pandemic. This notice was not renewed after six months and did not need consideration by the Committee.

Following advice from the Office of the Director of Public Health, on 1 April 2010 a Gazette notice was published to widen public access to oseltamivir to include the month of April and remove the requirement for the ill patient to be present in the pharmacy. Modelling from the northern hemisphere postulated that seasonal influenza was likely to arrive early in 2010. Oseltamivir was classified as a prescription medicine; except when sold in a pharmacy between the months of April to September inclusive by a registered pharmacist who is satisfied that the medicine is for the treatment of a consumer who is resident in New Zealand, is 12 years of age or more, and currently has the symptoms of influenza. Further advice confirmed that seasonal influenza may not have reached its peak in 2010 and so on 9 September 2010 a Gazette notice was published to widen public access to oseltamivir to include the months of October and November. Further advice confirmed that it would be reasonable to extend the Gazette notice so this classification of oseltamivir was gazetted again on 24 February 2011 and 8 August 2011. Again these classifications did not need consideration by the Committee.

At the 46^th meeting on 15 November 2011, the Committee recommended that the classification of oseltamivir as a restricted medicine; for the treatment of a consumer who is in New Zealand, is 12 years of age or more, and currently has the symptoms of influenza, should be added to the agenda of the next meeting.

At the 47^th meeting on 1 May 2012, the Committee recommended that a submission to reclassify oseltamivir as a restricted medicine; for the treatment of a consumer who is in New Zealand, is 12 years of age or more, and currently has the symptoms of influenza or is at risk of contracting influenza, was anticipated at the next meeting. Also that this submission for reclassification should include information for consumers and appropriate pharmacist advice.

Oseltamivir is currently classified as prescription; except when sold in a pharmacy between the months of April to November inclusive by a registered pharmacist who is satisfied that the medicine is for the treatment of a consumer who is resident in New Zealand, is 12 years of age or more, and currently has the symptoms of influenza.

Comments

Two pre-meeting comments were received during the consultation period. These comments supported the reclassification proposal for the following reasons:

1. allowing pharmacy access to Tamiflu will ensure that patients can access it efficiently and conveniently
2. the reclassification will reduce visits to general practice and the number of hospital admissions which could be a considerable cost saving for the New Zealand health system
3. early treatment of influenza is indicative of greater efficacy of treatment
4. pharmacists are well placed to give advice on prevention and immunisation
5. recent research has shown that five years of non-prescription availability of oseltamivir in New Zealand has not resulted in any significant change in the development of resistance nor in the reduction of rates of influenza immunisation
6. the reclassification will increase the availability of Tamiflu in the event of a pandemic
7. pharmacists have supplied Tamiflu professionally and appropriately
8. influenza infection is not limited to specific months of the year.

Discussion

The Committee noted Tamiflu had been available in a pharmacy from a pharmacist with a seasonal requirement for a number of years already. The evidence provided with the submission supported the sale of Tamiflu by a pharmacist to patients with influenza who meet the clinical diagnostic criteria in the algorithm.

Prophylaxis was an important component of the submission. It was noted by the Committee that one of the key studies included with the submission on prophylaxis only displayed a small significant difference in the effectiveness of Tamiflu.

The observers confirmed that post exposure prophylaxis essentially referred to early treatment. It was not expected that Tamiflu would be used for prophylaxis more than treatment and the reason for adding it to the classification statement was a marketing one. The observers also confirmed the treatment algorithm would determine whether a patient had been in close contact with an infected person or whether they were immunised already. Prophylaxis had been added to the algorithm in terms of treatment efficacy.

The risk of resistance was well covered in the submission. Data had been provided that demonstrated resistance occurred as a result of random DNA replication. The evidence indicated random viral mutation is the most likely cause of the emergence of resistance, not the use of Tamiflu. Although there was evidence of transient resistance strains emerging (more commonly with Zanamivir). The observers confirmed that resistance was far less with Tamiflu.

Oseltamivir has an established safety profile and there is low risk of misuse.

Tamiflu is intended to be used as an adjunct to the influenza vaccination programme. Although concern was expressed over the impact of Tamiflu on the immunisation programme. Widening access may change the way Tamiflu is managed.

The Committee discussed the duration of availability and the removal of the months in which Tamiflu can be sold from the classification statement. The Committee agreed this would not be an issue. People travel to and from New Zealand from other countries with influenza and approval of the application would result in treatment being available year round which would add to the public health benefit.

The key issue the Committee discussed was the need to access oseltamivir quickly on exposure, which supported the need for more convenient access. Organising a visit to a general practitioner in the effective treatment time window was often difficult for a patient.

The article presented to the Committee under agenda item 10.1, Innovations from 'down-under': A focus on prescription to non-prescription medicine reclassification in New Zealand and Australia (Gauld et al 2012), was timely as it reinforced the reclassification request. This review indicated pharmacies in New Zealand have acted and continue to act responsibly with Tamiflu in the current treatment guidelines.

The observers queried whether a different data sheet would be required for a prescription product, and a restricted product. It was confirmed that two separate data sheets would not be required. A number of comments were made on the proposed labelling in the submission. However, at present the labels are harmonised with those in Australia so to recommend any change would result in not being harmonised.

The Committee concluded that overall the benefits of reclassification far outweighed any risk and that oseltamivir in 75 mg powder filled capsules should be reclassified from prescription medicine to restricted medicine, in a pack of up to 10 capsules, for the treatment or prophylaxis of influenza in adults and children aged 13 years and older.

Recommendation

That oseltamivir in 75 mg powder filled capsules should be reclassified from prescription medicine to restricted medicine, in a pack of up to 10 capsules, for the treatment or prophylaxis of influenza in adults and children aged 13 years and older.

7 NEW MEDICINES FOR CLASSIFICATION

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

7.1 Abiraterone acetate - Zytiga 250 mg tablet

Zytiga tablets contain 250 mg of the active ingredient abiraterone acetate. Abiraterone decreases serum testosterone and other androgens to levels lower than those achieved by the use of luteinising hormone-releasing hormone antagonists alone or by orchiectomy.

Zytiga is indicated with prednisone or prednisolone for:

1. the treatment of patients with metastatic castration resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy
2. the treatment of patients with metastatic advanced prostate cancer (castration resistant prostate cancer) who have received prior chemotherapy containing a taxane.

Abiraterone acetate is not included in the Standard for the Uniform Scheduling of Medicines and Poisons (1 September 2012) in Australia.

Recommendation

That abiraterone acetate should be classified as a prescription medicine.

7.2 Vilanterol - Relvar™ Ellipta™ 100mcg/25mcg and 200mcg/25mcg powder for inhalation

Relvar™ Ellipta™ is a plastic inhaler containing two double foil blister strips. Each foil strip contains 14 or 30 regularly distributed blisters with one strip containing 100 or 200 mcg of fluticasone fluorate and the other strip containing 25 mcg of vilanterol.

Fluticasone is already classified as a prescription and pharmacy-only medicine in New Zealand and Australia.

Vilanterol, as trifenate, is a selective long-acting, beta₂-adrenergic agonist.

Relvar™ Ellipta™ is indicated for:

1. the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination product (long-acting beta₂-agonist and inhaled corticosteroid) is appropriate
2. symptomatic treatment of patients with Chronic Obstructive Pulmonary Disease with a FEV₁<70% predicted normal (post-bronchodilator) in patients with an exacerbation history.

Vilanterol is not included in the Standard for the Uniform Scheduling of Medicines and Poisons (1 September 2012) in Australia.

Recommendation

That vilanterol should be classified as a prescription medicine.

8 HARMONISATION OF NEW ZEALAND AND AUSTRALIAN SCHEDULES

8.1 New chemical entities which are not yet classified in New Zealand

8.1.1 Axitinib

Axitinib is an antineoplastic agent and inhibits the activity of tyrosine kinase including members of the vascular endothelial cell growth factor receptors (VEGF)-1, (VEGF)-2 and (VEGF)-3.

Axitinib is indicated for the treatment of renal cell carcinoma in the United Kingdom and the United States. The proposed indication in Australia was for the treatment of patients with advanced renal cell carcinoma.

In Australia in February 2012, the Delegate decided to include axitinib in Schedule 4 (prescription medicine) with an implementation date of 1 September 2012.

Recommendation

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

8.1.2 Cobicistat

Cobicistat is a new potent and selective inhibitor of human cytochrome P450 3A (CYP3A) enzyme. It is suitable for use in boosting anti-HIV drugs without risking selection of potential drug-resistant HIV variants.

Cobicistat is intended to be used in fixed dose combination tablet of elvitegravir / emtricitabine / tenofovir for the treatment of HIV-1 infection in adults who are antiretroviral naïve or have no known substitutions associated with resistance to the individual components.

In Australia in February 2012, the Delegate decided to include cobicistat in Schedule 4 (prescription medicine) with an implementation date of 1 September 2012.

Recommendation

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

8.1.3 Elvitegravir

Elvitegravir is an integrase inhibitor. Integrase is one of three enzymes like protease and reverse transcriptase, essential for viral replication. Integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells.

Elvitegravir is intended to be used in fixed dose combination tablet of cobicistat /emtricitabine / tenofovir for the treatment of HIV-1 infection in adults.

In Australia in February 2012, the Delegate decided to include elvitegravir in Schedule 4 (prescription medicine) with an implementation date of 1 September 2012.

Recommendation

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

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

The Committee noted that the Delegate had also made the following final decisions:

1. paracetamol - the maximum pack size for sale of paracetamol as a general sale medicine should be 10 g (which harmonised with New Zealand)
2. pantoprazole - should not be reclassified from Schedule 3 (restricted medicine) to Schedule 2 (pharmacy-only medicine) when 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 14 days' supply (which did not harmonise with New Zealand)
3. medicines used by Podiatrists (amorolfine, ciclopirox, clotrimazole, econazole, isoconazole, ketoconazole, miconazole, nystatin, terbinafine and tioconazole) - the pharmacy-only classification of medicines used by Podiatrists should not include the wording 'except when sold in practice by a podiatrist', or words of similar meaning (which did not harmonise with New Zealand).

8.2.1 Decisions by the Delegate - May 2012

a. Adrenaline

Preparations for injection should be excluded from the current exemption from scheduling for preparations containing 0.02% or less of adrenaline (ie, preparations for injection containing 1% or less of adrenaline would be Schedule 3 (restricted medicine) and above 1% would be Schedule 4 (prescription medicine)).

The Committee considered harmonising with the above classification.

The Committee noted there were two products currently marketed as general sale in New Zealand that would be affected by the proposed reclassification.

At the 22^nd meeting on 10 November 1999, in order to harmonise with Australia the Committee recommended that adrenaline be classified as:

• prescription; in medicines containing more than 1%
• restricted; in medicines containing 1% or less and more than 0.02%
• general sale; in medicines containing 0.02%.

Adrenaline is currently classified as:

• prescription; in medicines containing more than 1%
• restricted; in medicines containing 1% or less and more than 0.02%
• general sale; in medicines containing 0.02%.

Given the information provided for consideration, the Committee agreed by majority vote that there was no risk in harmonising with Australia. Preparations for injection containing adrenaline should be excluded from the current exemption from scheduling for preparations containing 0.02% or less of adrenaline (ie, preparations for injection containing 1% or less of adrenaline should be restricted medicines and preparations above 1% should be prescription medicines). The reclassification would result in the two products currently marketed being reclassified as restricted medicines.

Recommendation

That preparations for injection containing 1% or less of adrenaline should be reclassified as restricted medicines and preparations above 1% should be reclassified as prescription medicines.

b. Ciclopirox

Ciclopirox, in preparations for application to the nail containing 8% or less of ciclopirox, should be rescheduled from Schedule 3 (restricted medicine) to Schedule 2 (pharmacy-only medicine).

The Committee considered harmonising with the above classification.

The Committee noted there were three products currently marketed as restricted in New Zealand that would be affected by the proposed reclassification.

At the 30^th meeting on 26 November 2003, the Committee recommended that the classification of ciclopirox for external use should be changed to allow products containing 2% or less to be sold as pharmacy-only medicines.

At the 46^th meeting on 15 November 2011, the Committee recommended that the pharmacy-only classification of ciclopirox should include the wording 'except when supplied by a Podiatrist' or words of similar meaning.

Ciclopirox is currently classified as:

• prescription; except for external use
• restricted; for external use in medicines containing more than 2%
• pharmacy-only; for external use in medicines containing 2% or less except in medicines for tinea pedis only or when sold in practice by a podiatrist registered with the Podiatrists Board
• general sale; for external use in medicines for tinea pedis only or when sold in practice by a podiatrist registered with the Podiatrists Board.

The Committee agreed to harmonise with Australia, that ciclopirox, in preparations for application to the nail containing 8% or less of ciclopirox, should be reclassified from restricted medicine to pharmacy-only medicine.

Recommendation

That ciclopirox, in preparations for application to the nail containing 8% or less of ciclopirox, should be reclassified from restricted medicine to pharmacy-only medicine.

8.2.2 Decisions by the Delegate - June 2012

No harmonisation decisions relevant to the Committee were made by the Delegate.

8.2.3 Decisions by the Delegate - August 2012

No harmonisation decisions relevant to the Committee were made by the Delegate.

9 FOR THE NEXT MEETING

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

1. the Committee will discuss the factors when considering a medicine for reclassification for non-prescription sale using the paper put together by Medsafe
2. a revised submission to reclassify bifonazole, so that the pharmacy-only classification includes the wording 'except when sold in practice by a podiatrist registered with the Podiatrists Board', would be considered if submitted
3. a revised submission to reclassify diphtheria, tetanus and pertussis (acellular, component) vaccine (Tdap), in a single dose from prescription medicine to prescription medicine except when administered to a person aged 18 years or over by a pharmacist who has successfully completed the Immunisation Advisory Centre vaccinator course and is complying with the immunisation standards of the Ministry of Health, would be considered if submitted
4. a revised submission to reclassify ibuprofen, when in liquid oral suspension in sachets each containing 200 mg or less of ibuprofen for use in adults or children 12 years of age and older, from pharmacy-only medicine to general sale medicine would be considered if submitted
5. the 49^th meeting would be the fourth and last meeting that would pilot having observers during reclassification submissions - the Committee will review this pilot at the next meeting using feedback from the companies involved.

10 GENERAL BUSINESS

10.1 Innovations from 'down-under': A focus on prescription to non-prescription medicine reclassification in New Zealand and Australia (Gauld et al 2012)

An article from SelfCare, the journal of consumer led health from the United Kingdom, was presented to the Committee for information (Gauld N, Kelly F, Emmerton L, et al. 2012. Innovations from 'down-under': A focus on prescription to non-prescription medicine reclassification in New Zealand and Australia. SelfCare 3(5): 87-112).

11 DATE OF NEXT MEETING

To take place on a Tuesday in April 2013. The Secretary would email members for their availability.

There being no further business, the Chair thanked members and guests for their attendance and closed the meeting at 3:45pm.