Revised: 23 May 2013

Committees

Minutes of the 44th meeting of the Medicines Classification Committee - 2 November 2010

HELD IN THE MEDSAFE BOARDROOM, LEVEL 6, DELOITTE HOUSE, 10 BRANDON STREET, WELLINGTON. COMMENCING AT 9:30am

Valid objections have been received regarding the following recommendations:

6.2 Guaiphenesin 600 mg and 1200 mg modified release tablets
That the labelled warning regarding a potential risk of developing kidney stones at high doses should not be removed.

8.2.1b Red yeast rice
That lovastatin should be added to the New Zealand Schedule as a prescription medicine.
That monacolin K should be added to the New Zealand Schedule as a prescription medicine.
That Medsafe should consider the wording of monacolin K as a prescription medicine so that any foodstuffs would not be inadvertently captured.

8.3.2 Paracetamol
That New Zealand should not increase the maximum pack size for sale of paracetamol as a general sale medicine from 10 g to 12.5 g in order to harmonise with the less restrictive Australian classification.

These items will therefore be added to the agenda of the next meeting as matters arising for further consideration.

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Present:

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

In Attendance (from Medsafe):

Mrs Alison MacDonald (Senior Advisor Science, Over-the Counter Medicines)
Dr Susan Martindale (Principal Advisor, Regulation)
Mrs Mary Miller (Senior Advisor Science, Over-the Counter Medicines)
Mrs Marie Prescott (Advisor Science, Over-the Counter Medicines)

Apologies:

Dr Mark Peterson

1 WELCOME

The Chair opened the 44^th meeting at 9:30am and welcomed members and guests. The Chair welcomed Dr Yousuf as the new Ministry of Health member of the Committee.

2 APOLOGIES

Apologies were received from Dr Peterson.

3 CONFIRMATION OF THE MINUTES OF THE 43^RD MEETING HELD ON TUESDAY 13 APRIL 2010

The minutes of the 43^rd meeting were accepted as a true and accurate record. The minutes were signed and dated by the Chair.

4 DECLARATION OF CONFLICTS OF INTEREST

The Conflict of Interest forms were returned to the Secretary.

The following conflicts of interest were declared:

1. One member declared a personal interest with fampridine. The Committee agreed that, because the interest was not for financial gain, this would not be considered a conflict of interest and so the member could participate fully in the discussion during Agenda Item 7.3.
2. One member declared a potential conflict with Agenda Item 5.6 because they were involved, through a role with a District Health Board, in the proposal to reclassify vitamin D in tablets containing 1.25 mg of colecalciferol. The Chair stated members of the Committee were encouraged to make their own suggestions for submissions of reclassification. The member would make no financial gain if the reclassification was recommended. It was agreed that the member could fully participate in the discussion at this meeting because there would only be a recommendation made on whether to put the item on the agenda of the next meeting.
3. The same member declared a potential conflict with Agenda Item 6.4, omeprazole 10 mg tablets. A financial reward had been received from the New Zealand College of Pharmacists for presenting part of the education package when omeprazole was reclassified from prescription to restricted medicine. It was agreed that, because of the potential for further financial gain to be received in the future if they were involved in the education process if omeprazole was reclassified, the member could participate in discussion but not vote on any recommendation.
4. Another member declared previous job roles within the pharmaceutical industry, in various roles for a number of pharmaceutical companies. It was decided that these posed no current conflict of interest because all of the roles had been undertaken more than five years ago.
5. That same member declared a potential conflict with ginkgo biloba. They had completed the clinical evaluation for Medsafe, and had previously reviewed ginkgo biloba in Europe. It was decided that the member could participate in the discussion during Agenda Item 5.3, but not vote on any recommendation.

All other members declared they had no additional interests which would pose a conflict with any of the items on the agenda.

5 MATTERS ARISING

5.1 Objections to recommendations made at the 43^rd meeting

5.1.1 Ipecacuanha
(Cough and Cold medicines, Medsafe)

Weleda (New Zealand) Limited proposed an amendment be made to the Committee's recommendation that ipecacuanha should be reclassified from general sale medicine to pharmacy-only medicine for the treatment of the symptoms of cough and cold in children aged 6-12 years. The amendment proposed was that a dosage limit should be included in the reclassification so products with an alkaloid content of less than 40 mcg per dose were excluded and remained general sale medicines.

The reason for the proposal was that there were no known safety issues with ipecacuanha at this level.

Weleda suggested that the proposed amendment be accepted on the basis of:

1. the very low risk profile for ipecacuanha at this concentration
2. some indication of efficacy from the long history of traditional use
3. the need to create a cut-off point so as not to catch low dose homeopathic and anthroposophic medicines in scheduling
4. keeping Weleda Cough Elixir on a similar regulatory basis to other complimentary medicine cough products.

The submission in support of the proposal contained the proposed amendment, summary, background to the proposal, substantiation (safety, history of adverse reaction reports and efficacy), and the equivalent standards to other complimentary medicines in New Zealand and Australia.

At its 59^th meeting in June 2010, the Australian National Drugs and Poisons Schedule Committee agreed, amongst others, that:

1. the use of certain substances (including dextromethorphan, ipecacuanha and phenylephrine) in preparations for treating cough and cold be rescheduled to prescription medicine for use in children less than two years of age, restricted medicine for use in children aged from two to six years of age and pharmacy-only medicine for use in children and adults above six years of age
2. the rescheduling should apply only where it would not result in less restrictive scheduling
3. use of ammonia, bromhexine and guaiphenesin in preparations for treating cough and cold did not need to be rescheduled.

A dosage limit was not included in the rescheduling of ipecacuanha in Australia.

One pre-meeting comment had been received during the consultation period and this had no objection to the proposal. 40 mcg per dose was a very low dose of ipecacuanha used for its soothing, cramping relieving effects rather than the expectorant or emetic properties of medicines containing higher doses. The dose recommended by Martindale as an expectorant was up to 1,400 mcg and the emetic dose up to 42,000 mcg of total alkaloids which was significantly higher.

One Committee member queried where the alkaloid content of less than 40 mcg per dose had been derived from, and whether it would be necessary for Medsafe to complete an evidence based review of this cut-off point. It was explained that there was little safety and efficacy data at the level of 40 mcg. It appeared that the proposed cut-off point was arbitrary from a safety perspective and was suggested to broadly align with the product manufactured by Weleda. Applications for reclassification based on cut-off points contained in products manufactured by a submitting company form the basis of many submissions for reclassification.

The Committee agreed Weleda had made a reasonable argument that a dosage limit should be included in the reclassification of ipecacuanha so products with an alkaloid content of less than 40 mcg per dose were excluded and remained general sale medicines. The Committee accepted the argument that the known risks of toxicity for ipecacuanha were dose related. The proposed cut-off dose and pack size meant it is extremely unlikely that toxicity would be seen with the proposed product even if the whole pack was consumed. It was also noted the long history of traditional use of ipecacuanha at the proposed dose without evidence of toxicity. The Committee recommended that this reclassification should come into effect on 1 May 2011, alongside the reclassification of dextromethorphan and phenylephrine.

Recommendation

• That ipecacuanha should be reclassified from general sale medicine to pharmacy-only medicine for the treatment of the symptoms of cough and cold in children aged 6-12 years.
• That a dosage limit should be included in the reclassification of ipecacuanha so products with an alkaloid content of less than 40 mcg per dose were excluded and remained general sale medicines.
• That this reclassification should come into effect on 1 May 2011.

5.2 Flurbiprofen 8.75 mg lozenges
(Strepfen, Reckitt Benckiser (New Zealand) Limited)

At the 43^rd meeting the Committee considered a submission for the reclassification of flurbiprofen 8.75 mg lozenges from pharmacy-only medicine to general sale medicine, for the relief of pain, swelling and inflammation associated with severe sore throats. The Committee recommended that the submission would be reconsidered if Reckitt Benckiser provided data confirming that consumers could clearly differentiate and understand the differences between Strepfen and cough and cold unmedicated preparations such as Strepsils.

Two pre-meeting comments had been received during the consultation period and neither supported the reclassification proposed. Concern was emphasised about the potential for consumer confusion between Strepfen and unmedicated preparations such as Strepsils, with consequent adverse impacts on consumer safety. In addition, the submissions noted the proposed warning statements on the label of Strepfen lozenges (e.g. check with your pharmacist or doctor if you are receiving regular treatment with other medications) were not what was expected on a general sale product. A pharmacy-only classification was the least restrictive for a medicine whilst retaining its display and sale within the environment of a pharmacy.

One Committee member had bought examples of both Strepfen and Strepsils and it was agreed that the packets looked similar.

Reckitt Benckiser had contacted the Secretary and stated that further data would be provided at a later unspecified date. However, the Committee agreed that, because of the comments received and that the same submission was being discussed as a harmonisation issue during Agenda Item 8.2.2a, the reclassification of flurbiprofen 8.75 mg lozenges would not be carried forward to the next agenda as a matter arising. However, additional data could be submitted by Reckitt Benckiser in a new submission to the Committee.

Recommendation

No recommendation was required.

5.3 Ginkgo biloba

Ginkgo biloba was presented to the Committee at the 42^nd meeting for information only. Medsafe had received a New Medicine Application for a medicine (Tebonin) containing a standardised extract of ginkgo biloba (EGb761). The Committee recommended that the classification of ginkgo biloba be deferred so that the Committee could consider further data relating to the classification.

The Medicines Assessment Advisory Committee had considered the new medicine application for Tebonin, under section 20 of the Medicines Act 1981, at their 91^st meeting on 6 October 2010. The Medicines Assessment Advisory Committee considers applications for the Minister's consent or provisional consent to the distribution of a new medicine referred to it under section 22(2) of the Medicines Act 1981. It was recommended that the Minister of Health should refuse consent to the distribution of the medicine Tebonin. The recommendation was due to

1. no clearly defined mechanism of action
2. a lack of dose finding information
3. broad and poorly defined indications
4. insufficient clinical trial data which contained small inconsequential data
5. a lack of evidence of safety.

The classification of ginkgo biloba was considered now that additional data had been supplied by Medsafe:

1. further information on the safety and toxicity of ginkgo biloba, 20 July 2010
2. referral memo to the Medicines Assessment Advisory Committee, 31 May 2010
3. evaluation report of the administrative, chemical, pharmaceutical and bioavailability data of the New Medicine Application for Tebonin, 31 May 2010
4. Medical Advisor's report on Tebonin, March 2009
5. review the of clinical evaluation, February 2010
6. letter addressed to the applicant company requesting further information, 25 February 2010
7. pharmacology, pharmacokinetics and toxicology sections of the New Medicine Application, 18 December 2008.

The Committee noted that in Europe, as in Australia, there is a pathway for the assessment and approval of herbal medicines which does not exist in New Zealand. In Europe Tebonin was assessed as a herbal medicine. In Australia, ginkgo biloba is included in the schedule of substances permitted to be included in listed medicines by the Therapeutic Goods Administration. However, in New Zealand the Medicines Act 1981 requires Medsafe to evaluate Tebonin as a new medicine and, unlike these other jurisdictions, safety and efficacy data was required to support the application.

The Committee discussed the issue of the potential for ginkgo biloba to interact with warfarin and also whether its use could lead to increased reports of bleeding. The Committee noted that published systematic studies of ginkgo biloba had not shown an increased risk of bleeding or interaction with warfarin leading to increased anticoagulation. In the European Union labelling of ginkgo biloba products require cautionary statements advising:

1. the discontinuation of ginkgo biloba at least two weeks prior to surgery
2. that clotting parameters are assessed prior to surgery.

The data presented to the Committee demonstrated minimal risk of side effects associated with use of ginkgo biloba, with the most common adverse effect being low levels of hypersensitivity and allergic reactions. In the Committee's opinion the available safety data did not support the classification of either ginkgo biloba, or the standardised extract (EGb761), as anything other than general sale.

Ginkgo biloba was already being sold within New Zealand as a dietary supplement with supportive claims. It was noted by the Committee that their decision would affect all products that contained ginkgo biloba, and not just those with therapeutic claims. Classifying ginkgo biloba into the Medicines Act 1981 would make it a medicine. The Committee agreed there was insufficient evidence of toxicity or harm associated with use of ginkgo biloba to warrant its classification and did not support adding it to the First Schedule of the Medicines Regulations 1984.

Recommendation

That ginkgo biloba should not be added to the First Schedule of the Medicines Regulations 1984.

5.4 Minoxidil 5% solution
(Regaine for men, Johnson & Johnson Pacific)

At the 43^rd meeting the Committee considered a submission for the reclassification of minoxidil 5% solution from pharmacy-only medicine to general sale medicine for the treatment of androgenetic alopecia (common baldness) in healthy men and women.

The submission was not reconsidered because the company did not provide improved labelling appropriate for general sale. It would not be carried forward to the next agenda.

Recommendation

No recommendation was required.

5.5 Sedating antihistamines

It had been brought to Medsafe's attention that potential confusion could arise between the pharmacy-only classification statement for sedating antihistamines and the recent requirement for labels in oral cough and cold medicines to include a contraindication for use in children under six years of age. It was not the intent of the Cough and Cold Review Group to capture sedating antihistamines when used to treat allergy within this labelling requirement.

The sedating antihistamines affected are brompheniramine, chlorpheniramine, dexchlorpheniramine, diphenhydramine, doxylamine, pheniramine, promethazine, trimeprazine and triprolidine.

Clarification of the Committee's decisions as of 16 December 2005 is on the Medsafe website. Sedating antihistamines were classified as:

• prescription; except when specified elsewhere in this Schedule
• restricted; for oral use except when specified elsewhere in this Schedule
• pharmacy-only; for oral use when combined with one or more therapeutically active ingredients for the treatment of coughs, colds or influenza when at least one of the other active ingredients is a sympathomimetic decongestant or in a day / night pack containing <sedating antihistamine substance> in the bed-time dose and in preparations for adults and children over two years of age.

At the 34^th meeting on 9 June 2006, it was recommended that sedating antihistamines should be classified as prescription medicines when indicated either singly or in combination for use in children under two years of age. At the 35^thmeeting on 9 June 2006, it was recommended that the indications for the use of sedating anti-histamines, i.e. the treatment of coughs, colds or influenza, as pharmacy-only medicines be removed from the Schedule. At the same meeting it was recommended that diphenhydramine and other sedating antihistamines contained in the night time dose of day / night preparations should be pharmacy-only medicines only when in the same primary container. No recommendation was made at the 36^th meeting on 8 February 2007. At the 37^th meeting on 17 May 2007, following considerable discussion, the Committee stood by its earlier decision that sedating antihistamines should be prescription medicines when used for children under two years of age. At the 38^th meeting on 14 December 2007, it was recommended that Medsafe should be asked to review the labelling of all sedating antihistamine products to ensure that these were contraindicated in children under two years of age and that there was a warning statement about use with other cough and cold medicines.

Sedating antihistamines are currently classified as

• prescription; except when specified elsewhere in this Schedule
• restricted; for oral use in adults or children over two years of age except when specified elsewhere in this Schedule
• pharmacy-only; for oral use in medicines for adults and children over two years of age when combined in the same container with one or more other therapeutically active ingredients either when in the bed-time dose of a day/night pack containing <sedating antihistamine substance> or when at least one of the other therapeutically active ingredients is a sympathomimetic decongestant.

At its 59^th meeting in June 2010, the Australian National Drugs and Poisons Schedule Committee considered the scheduling of antihistamines (brompheniramine, chlorpheniramine, dexchlorpheniramine, diphenhydramine, doxylamine, pheniramine, promethazine and triprolidine) during the discussions on cough and cold medication. It was agreed, amongst others, that:

1. the use of certain substances (including brompheniramine, chlorpheniramine, dexchlorpheniramine, diphenhydramine, doxylamine, pheniramine, promethazine and triprolidine) in preparations for treating cough and cold be rescheduled to prescription medicine for use in children less than two years of age, restricted medicine for use in children aged from two to six years of age and pharmacy-only medicine for use in children and adults above six years of age
2. the rescheduling should apply only where it would not result in less restrictive scheduling.

Only trimeprazine had not been discussed.

The Committee considered whether the following actions together could resolve the issue:

1. remove the words 'for adults and children over two years of age' from the pharmacy-only classification statement
2. add to the New Zealand Regulatory Guidelines for Medicines the requirement for the statement 'must not be used in children under six years of age' to be added to the label when the sedating antihistamine is used for the treatment of the symptoms of cough and cold.

One pre-meeting comment had been received during the consultation period. It was suggested it would be important that the 'not for under six years' age restriction on the use of sedating antihistamines in cough and cold preparation was not permitted to confuse or restrict their use in the treatment of allergic conditions or for the prevention or treatment of motion sickness in adults and children over two years of age. This included their sale as single ingredient restricted medicines.

The Committee decided that removing the words 'for adults and children over two years of age' from the pharmacy-only classification statement would not work. Keeping a specific age in the classification statement provided clarity and would give certainty to pharmacists when asked for advice on the use of sedating antihistamines as an anti-allergy treatment.

It was agreed that the pharmacy-only Schedule entry for sedating antihistamines (which deals only with the use of these products in combination cough and cold medicines) should be amended to limit use to children over six years of age, i.e.:

• pharmacy-only; for oral use in medicines for adults and children over six years of age when combined in the same container with one or more other therapeutically active ingredients either when in the bed-time dose of a day/night pack containing <sedating antihistamine substance> or when at least one of the other therapeutically active ingredients is a sympathomimetic decongestant.

In addition, the Committee recommended that the statement 'must not be used in children under six years of age' should be added to the labelling guideline within the New Zealand Regulatory Guidelines for Medicines when the sedating antihistamine is used for the treatment of the symptoms of cough and cold.

Recommendation

• That sedating antihistamines should be classified as pharmacy-only; for oral use in medicines for adults and children over six years of age when combined in the same container with one or more other therapeutically active ingredients either when in the bed-time dose of a day/night pack containing <sedating antihistamine substance> or when at least one of the other therapeutically active ingredients is a sympathomimetic decongestant.
• That the requirement for the statement 'must not be used in children under six years of age' to be added to the label when the sedating antihistamine is used for the treatment of the symptoms of cough and cold be included in the New Zealand Regulatory Guidelines for Medicines.

5.6 Vitamin D (colecalciferol)
Cal.D.Forte 1.25 mg coated tablet

It had been suggested by a Committee member that it may be appropriate to reclassify vitamin D, in tablets containing 1.25 mg of colecalciferol, from prescription medicine to restricted medicine for the prevention and treatment of vitamin D deficiency states in adults.

The Secretary had written to the sponsor company of Cal.D.Forte asking if they would like to support the proposal by making a formal submission to the Committee. However a response had not been received.

Vitamin D is currently classified as:

• prescription; for internal use in medicines containing more than 25 µg per recommended daily dose except in parenteral nutrition replacement preparations
• general sale; for external use; for internal use in medicines containing 25 µg or less per recommended daily dose; in parenteral nutrition replacement preparations.

At its 57^th meeting in October 2009, the Australian National Drugs and Poisons Schedule Committee considered the scheduling of vitamin D. It was decided that the current scheduling of vitamin D remained appropriate, i.e. prescription medicine; for human internal therapeutic use except in preparations containing 25 µg or less of vitamin D per recommended daily dose.

The Committee considered whether there was sufficient potential benefit in the proposal to reclassify vitamin D to warrant asking Medsafe to make a submission proposing reclassification. There had been a significant amount of research in New Zealand investigating who was most at risk from vitamin D deficiency including research evidence that use of vitamin D may deliver benefit through falls prevention. However, it was noted that this research may have been confounded by a number of factors.

The Committee agreed that there was enough evidence of potential benefit for Medsafe to be asked to take the submission forward without the support of industry. However, it was recognised that more data would be required to provide sufficient data to complete an application. The following suggestions were made which could help with the submission from Medsafe:

1. specify the daily dose
2. seek advice from the Pharmaceutical Society of New Zealand
3. obtain falls statistics from the Accident Compensation Corporation
4. contact the key researchers in New Zealand including Associate Professor Robert Scragg (Epidemiology and Biostatistics, Faculty of Health and Medical Sciences, at the University of Auckland) and Professor Ian Reid (Professor of Medicine and Endocrinology at Auckland Medical School) who is a prominent figure in international bone research
5. examine the Cochrane review of vitamin D and the health of older people
6. include the National Drugs and Poisons Schedule Committee's analysis of vitamin D as a daily dose to inform the risk analysis of the submission.

Recommendation

That Medsafe should make a submission proposing the reclassification of vitamin D, in tablets containing 1.25 mg of colecalciferol, from prescription medicine to restricted medicine for the prevention and treatment of vitamin D deficiency states in adults.

6 SUBMISSIONS FOR RECLASSIFICATION

6.1 Aspirin
(Pharmacybrands Limited)

Purpose

This was a submission from Pharmacybrands Limited (the parent company for Life, Unichem, Amcal and Care Pharmacies in New Zealand) for the reclassification of aspirin, in solid dose preparations containing 150 mg or less of aspirin, from general sale medicine to pharmacy-only medicine for the inhibition of blood clotting and to reduce the risk of heart attack and stroke.

Background

Aspirin was considered but no recommendation was made at the 1^st meeting on 13 November 1984 and the 2^nd meeting on 19 March 1985.

At the 7^th meeting on 31 July 1990 and 1 August 1990, aspirin was reclassified as:

• Part I pharmacy (restricted); in enteric coated and slow release forms
• general sale; except in enteric coated and slow release forms.

At the 11^th meeting on 29 June 1993, the Committee recommended that:

1. aspirin when indicated for platelet aggregation should be classified in the same way as other aspirin
2. enteric coated aspirin in strengths of 300 mg and less become general sale
3. aspirin in enteric coated forms over 300 mg and in slow release forms remain restricted medicine.

No reclassification recommendations were made at the 19^th meeting on 20 May 1998 or the 37^th meeting on 17 May 2007.

At the 38^th meeting on 14 December 2007, the Committee recommended that aspirin should be classified as a prescription medicine when in combination with caffeine, paracetamol or salicylamide.

Aspirin is currently classified as:

• prescription; for injection; when combined with caffeine, paracetamol or salicylamide
• restricted; in slow release forms; in enteric coated forms containing more than 300 mg per dose form; except when specified elsewhere in this Schedule
• general sale; except when specified in the First Schedule to the Medicines Regulations 1984.

At its 59^th meeting in June 2010, the Australian National Drugs and Poisons Schedule Committee considered the scheduling of aspirin. Low dose aspirin (up to 150 mg daily) had been recommended for the prevention of serious vascular events, including myocardial infarction and stroke, in patients at high risk (e.g. acute and post myocardial infarction, angina, peripheral arterial disease, stroke or arterial fibrillation). At their 39^th meeting in October 2003, a Schedule 2 (pharmacy-only) entry was adopted to exempt from scheduling packets of 100 tablets or less of low dose aspirin (100 mg or less) for prevention of cardiovascular disease or inhibition of platelet aggregation. Any single active aspirin for prevention of cardiovascular disease or for the inhibition of platelet aggregation, which does not qualify for exemption, was caught by the Schedule 2 (pharmacy-only) entry. At the 59^th meeting they agreed that the current scheduling of aspirin remained appropriate.

The Committee noted an article in the New Zealand Herald, 'Heartache over aspirin', dated 29 August 2010 which described the submission.

Comments

Six pre-meeting comments were received during the consultation period. Four of these did not support the reclassification and made the following comments:

1. the submission lacked the safety data of increased risk to justify a classification change
2. low dose aspirin was currently unscheduled in other countries, including Australia
3. the evidence within the submission did not suggest that the current scheduling posed a significant risk to public health
4. warning statements, if not already provided, should be included to direct the consumer to their Doctor before using low dose aspirin for the prevention of a cardiovascular event.

The two which supported the reclassification made the following points:

1. recent reports indicated an unfavourable risk-benefit profile with routine use in primary prevention
2. pharmacists were well positioned to assess the risk and provide the necessary healthcare to consumers.

The Committee also noted a letter that had been written to Hon Tony Ryall, Minister of Health, on 30 August 2010. The concerned individual had read the article in the New Zealand Herald and requested that the Minister retain the status quo.

Discussion

The Committee were pleased that the pharmacy sector was engaging in the process and a submission for reclassification had been made.

However, concern was expressed that the reclassification of solid dose preparations containing 150 mg or less of aspirin only could paradoxically increase the risk. It was felt that consumers taking low dose aspirin could elect to continue purchasing aspirin products containing 300 mg from supermarkets and elect to split the tablet or to take the 300 mg strength. In some circumstances this would represent an increased dose of aspirin compared to the 75 mg low dose products currently available as general sale medicines.

The main thrust of the submission for the reclassification was that individuals need assistance from a healthcare professional, such as a pharmacist or general practitioner, in order to take low dose aspirin safety. The Committee noted that a pharmacy-only classification would not ensure contact with a healthcare professional, and as such provided a limited opportunity for the consumer's cardiovascular risk profile to be assessed by a pharmacist. The Committee noted that low dose aspirin was only indicated for use in secondary prevention of heart attack and stroke, and that patients with these conditions were often already engaged with the healthcare system.

The Committee discussed the example labelling provided with the submission. It was suggested that aligning New Zealand labelling of aspirin products with that used internationally and in Australia should be considered by Medsafe as an issue separate from scheduling.

Recommendation

• That aspirin, in solid dose preparations containing 150 mg or less of aspirin, should not be reclassified from general sale medicine to pharmacy-only medicine for the inhibition of blood clotting and to reduce the risk of heart attack and stroke.
• That Medsafe should look at the labelling of all aspirin products with respect to international alignment.

6.2 Guaiphenesin 600 mg and 1200 mg modified release tablets
(Mucinex, Reckitt Benckiser (New Zealand) Limited)

Purpose

This was a company submission requesting an additional classification of guaiphenesin, in modified release tablets containing 600 mg or 1200 mg of guaiphenesin (Mucinex) in packs containing more than five but not more than 10 days supply, as a pharmacy-only medicine for use as an expectorant which thins and loosens mucus (phlegm) to help relieve chest congestion.

The submission also proposed that the:

1. restricted medicine classification statement should be amended to 'for oral use in modified release form with a maximum recommended daily dose of not more than 2.4 g sold in a pack containing more than 10 days supply but not more than 30 days supply approved by the Minister or the Director-General for distribution as a restricted medicine'
2. labelled warning statement to seek medical advice if symptoms persist should be amended from 'after three days' to 'after five days'
3. labelled warning regarding a potential risk of developing kidney stones at high doses should be removed.

Background

At the 7^th meeting on 31 July 1990 and 1 August 1990, guaiphenesin was reclassified as:

• Part II pharmacy (pharmacy-only); in medicines containing more than 2% of guaiphenesin
• general sale; in medicines containing 2% or less of guaiphenesin.

At the 27^th meeting on 23 May 2002, the Committee recommended that guaiphenesin be classified as prescription medicine in liquid form containing more than 2% or solid dose form containing more than 200 mg.

At the 41^st meeting on 14 May 2009, the Committee recommended that:

• guaiphenesin should be reclassified from prescription medicine to general sale medicine when the pack size is limited to not more than five days' supply, in a modified release dosage form with a maximum daily dose of not more than 2400 mg, and in packs approved by the Minister or the Director-General for distribution as general sale medicines
• guaiphenesin should be reclassified from prescription medicine to restricted medicine when pack size is more than five days' but not more than 30 days' supply, in a modified release dosage form, a maximum daily dose of not more than 2400 mg is recommended and in packs approved by the Minister or the Director-General for distribution as restricted medicines
• Medsafe should be satisfied with data supporting efficacy, and with the proposed label warnings, of any modified release guaiphenesin product seeking consent to be sold as an over-the-counter medicine.

In the current submission, the sponsor company provided data and requested the Committee remove or amend three of the recommendations made at the 41^st meeting:

1. a labelled warning of the potential risk of developing kidney stones at higher doses
2. a five day supply limitation in the general sale classification
3. to seek medical advice if symptoms persist after three days.

At the 43^rd meeting on 13 April 2010, the Committee recommended that the current scheduling of guaiphenesin remained appropriate.

Guaiphenesin is currently classified as:

• prescription; for oral use in medicines containing more than 2% or 200 mg per dose form except when specified elsewhere in this Schedule; except for oral use in modified release form with a maximum recommended daily dose of not more than 2.4 g sold in a pack containing not more than 5 days supply approved by the Minister or the Director-General for distribution as a general sale medicine
• restricted; for oral use in modified release form with a maximum recommended daily dose of not more than 2.4 g sold in a pack containing more than 5 days supply but not more than 30 days supply approved by the Minister or the Director-General for distribution as a restricted medicine
• general sale; for oral use in medicines containing 2% or less or 200 mg or less per dose form; for oral use in modified release form with a maximum recommended daily dose of not more than 2.4 g sold in a pack containing not more than 5 days supply approved by the Minister or the Director-General for distribution as a general sale medicine.

At its 57^th meeting in October 2009, the Australian National Drugs and Poisons Schedule Committee confirmed that their current scheduling entries for modified release formulations of guaiphenesin remained appropriate. They did not harmonise with the recommendations made by the Committee at the 41^st meeting.

Comments

Two pre-meeting comments were received during the consultation period. One supported the reclassification proposed although expressed concern, and did not support, the proposed amendments to the restricted medicine classification and the labelled warning statements for reasons of consumer safety. The other did not support the proposal or the suggested amendment to packs of more than five days but not more than 30 days supply to be pharmacy-only medicine.

Discussion

The Committee did not support the proposal to create an additional classification of guaiphenesin, in modified release tablets containing 600 mg or 1200 mg of guaiphenesin (Mucinex) in packs containing more than five but not more than 10 days supply, as a pharmacy-only medicine for use as an expectorant which thins and loosens mucus (phlegm) to help relieve chest congestion. Nor did it support changing the restricted medicine classification statement to 'for oral use in modified release form with a maximum recommended daily dose of not more than 2.4 g sold in a pack containing more than 10 days supply but not more than 30 days supply approved by the Minister or the Director-General for distribution as a restricted medicine'. Continuing concerns about the possible off label use of guaiphenesin was the basis of their reason not to support significantly increasing pack size and introducing multiple levels of classification.

The Committee considered that it would be prepared to support a limited change in pack size to allow a pack containing 10 days or less to be available as a general sale medicine.

It was also agreed that the labelled warning statement to seek medical advice if symptoms persist could be amended from 'after three days' to 'after five days'. Although use of a 'three days' treatment period before seeking advice was consistent with other cough and cold products, the Committee considered that this period could be increased without additional safety concerns being raised.

The Committee did not agree that labelled warning regarding a potential risk of developing kidney stones at high doses should be removed. The submission included evidence that provided support for the warning that taking guaiphenesin for a long period of time increases the risk of developing kidney stones.

Recommendation

• That there should not be an additional classification of guaiphenesin, in modified release tablets containing 600 mg or 1200 mg of guaiphenesin (Mucinex) in packs containing more than five but not more than 10 days supply, as a pharmacy-only medicine for use as an expectorant which thins and loosens mucus (phlegm) to help relieve chest congestion.
• That the restricted medicine classification statement should not be amended to 'for oral use in modified release form with a maximum recommended daily dose of not more than 2.4 g sold in a pack containing more than 10 days supply but not more than 30 days supply approved by the Minister or the Director-General for distribution as a restricted medicine'.
• That the labelled warning statement to seek medical advice if symptoms persist should be amended from 'after three days' to 'after five days', however Medsafe would need to review the revised warning and pack insert.
• That the labelled warning regarding a potential risk of developing kidney stones at high doses should not be removed.

Secretary’s note
A valid objection has been received regarding the recommendation that the labelled warning regarding a potential risk of developing kidney stones at high doses should not be removed.

See the addendum to these minutes (at the top of this page) for further details.

6.3 Nicotine 1 mg and 15 mg volatile liquid and 1 mg spray
(Nicorette Inhaler and Nicorette QuickMist Mouth Spray, Johnson and Johnson (New Zealand) Limited)

Purpose

This was a company submission requesting the general sale classification of nicotine be amended from 'for transdermal use in chewing gum, lozenges or sublingual tablets' to 'for preparations for oromucosal or transdermal absorption'.

This amendment would result in the Nicorette Inhaler (containing 10 mg and 15 mg of nicotine) to be reclassified from pharmacy-only medicine to general sale medicine, and the Nicorette QuickMist Mouth Spray (containing 1 mg of nicotine) to be classified as a general sale medicine.

The submission argued that specific dosage forms do not differ significantly in their safety and efficacy compared to other oral nicotine replacement therapy formats which were general sale. The pharmacy-only and prescription classifications would remain unchanged.

Background

The Committee considered nicotine but did not make a recommendation at the 2^nd meeting on 19 March 1985.

At the 7^th meeting on 31 July 1990 and 1 August 1990, nicotine was reclassified as:

• Part II pharmacy (pharmacy-only); and its salts; for transdermal use
• general sale; and its salts; in chewing gum.

Nicotine was considered but no recommendations were made at the 8^th meeting on 6 December 1991, 9^th meeting on 28 May 1992, 10^th meeting on 11 November 1992 or the 11^th meeting on 29 June 1993.

At the 23^rd meeting on 25 May 2000, the Committee recommended that nicotine should be reclassified from pharmacy-only to general sale medicine when contained in chewing gum or transdermal patches for the purpose of smoking cessation. Objections had been received regarding this reclassification. These objections were not upheld because they had not been based on new safety data. At the 24^th meeting on 2 November 2000, the Committee recommended that nicotine lozenges should be classified as restricted medicine except when sold in a smoking cessation clinic run under the auspices of a registered medical practitioner, nurse, pharmacist or psychologist. At the 30^th meeting on 26 November 2003, the Committee recommended that nicotine in lozenges and sublingual tablets be reclassified from restricted to pharmacy-only medicine. At the 32^nd meeting on 25 November 2004, the Committee recommended that nicotine in medicines for smoking cessation should be reclassified from pharmacy-only to general sale medicine when in lozenges or sublingual tablets.

Nicotine is currently classified as:

• prescription; for nasal use except when sold from a smoking cessation clinic run under the auspices of a registered medical practitioner; in medicines other than for smoking cessation
• pharmacy-only; for inhalation except when sold from a smoking cessation clinic run under the auspices of a registered medical practitioner, nurse, pharmacist or psychologist
• general sale; for transdermal use or in chewing gum, lozenges or sublingual tablets.

The Australian National Drugs and Poisons Schedule Committee considered the same submission at its 58^th meeting in February 2010. They decided to amend the scheduling of nicotine to exempt oromucosal spray use, as an aid in withdrawal from tobacco smoking, from scheduling. This decision was confirmed at the 59^th meeting in June 2010.

Comments

Three pre-meeting comments were received during the consultation period and all supported the amendment proposed. It was suggested that the current wording of the general sale classification limited innovation in nicotine replacement therapy and without innovation there would be limited scope for attracting new smokers to quit smoking. One was uncertain about the implications for consumer safety because some of the nicotine in Nicorette inhaler may be deposited in the lungs. Another noted that the Nicorette Inhaler was not pressurised and accepted that the majority of the nicotine was absorbed bucally with less than 5% through the lungs. They recommended that the sponsor company discontinue this product when the QuickMist mouth spray is registered, or change the name to remove the word inhaler.

Discussion

Overall the Committee was comfortable with the submission. The data presented showed that the different dose forms were similar even though bioequivalence data had not been included in the submission.

While the Committee noted that the evidence supported higher quit rates when smoking cessation products were combined with support, e.g. via a doctor, pharmacist or Quitline, the evidence demonstrated that even as a solo intervention patient access to nicotine replacement therapy increases the rate of smoking cessation. Concern was expressed over the name of the Nicorette Inhaler and the Committee wanted it noted that they would encourage the company to reconsider this name. The major portion of the dose from the nicotine inhaler was deposited in the oral cavity and so use of the term 'inhaler' was potentially misleading.

Recommendation

That the general sale classification of nicotine should be amended from 'for transdermal use in chewing gum, lozenges or sublingual tablets' to 'for preparations for oromucosal or transdermal absorption'.

6.4 Omeprazole 10 mg tablet
(Losec, Bayer New Zealand Limited)

Purpose

This was a company submission requesting the reclassification of omeprazole, in tablets containing 10 mg or less of omeprazole, from restricted medicine to pharmacy-only medicine for the short-term, symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and over.

Training material was supplied with the submission which included clinical papers, information on the training, examples of questionnaires used and a DVD of the training seminar given in Wellington. The submission supported the current restrictions for the non-prescription sale of omeprazole.

Background

Omeprazole was classified as a prescription medicine at the 6^th meeting on 10 March 1987.

Omeprazole was considered but no recommendations were made at the 7^th meeting on 31 July 1990, 26^th meeting on 11 December 2001, 28^th meeting on 19 November 2002, 33^rd meeting on 9 June 2005, 35^th meeting on 9 June 2006 and the 38^th meeting on 14 December 2007.

At the 40^th meeting on 25 November 2008, the Committee recommended that tablets or capsules containing 10 mg or less of omeprazole should be reclassified from prescription to restricted medicine when sold in packs which have received the consent of the Minister or the Director-General to their sale as restricted medicines and are sold in the manufacturer's original pack.

At the 42^nd meeting on 3 November 2009, the Committee recommended that:

• tablets containing 20 mg of omeprazole or less should be classified as a restricted medicine when sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine
• the requirements for omeprazole to be classified as a restricted medicine should be inserted into the New Zealand Regulatory Guidelines for Medicines by Medsafe
• Medsafe should be satisfied with the proposed warning labels of any product containing omeprazole seeking consent for distribution as a restricted medicine.

Omeprazole is currently classified as:

• prescription; except when specified elsewhere in this Schedule
• restricted; in tablets or capsules containing 20 mg or less when sold in a pack approved by the Minister or the Director-General for distribution as a restricted medicine.

At its 58^th meeting in February 2010, the Australian National Drugs and Poisons Schedule Committee agreed to include omeprazole in Schedule 3 (restricted medicine) when in oral preparations containing 20 mg or less per dosage unit of omeprazole for the relief of heartburn and gastro-oesophageal reflux disease, in packs containing not more than 14 days of supply. This harmonised with the Committee's recommendation at the 41^st meeting.

Comments

Three pre-meeting comments were received during the consultation period, none of which supported the proposed reclassification. Two commented that it had only been in the past 12 months that the classification for 20 mg omeprazole had changed to restricted medicine and given pharmacists the opportunity to diagnose and offer short term treatment for the symptomatic relief of gastric-like reflux symptoms. The other highlighted the potential for adverse events from inappropriate use of omeprazole and referenced an article in Prescriber Update from June 2010 which reported an association between omeprazole treatment and hypomagnesaemia (www.medsafe.govt.nz/profs/PUArticles/OmeprazoleJune2010.htm).

Discussion

The Committee considered the submission a little premature because it was only at the last meeting that tablets containing 20 mg of omeprazole or less were recommended to be classified as a restricted medicine when sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine.

The difference between a 10 mg and 20 mg dose and whether the two product packs needed to be differentiated was discussed. The safety profile was the same at both doses, and the treatment regimen for both product packs included use of a dose of 20 mg. The company suggested in their submission that the requirements currently in the New Zealand Regulatory Guidelines for Medicines for omeprazole as a restricted medicine applied equally well to the 10 mg dose at the pharmacy-only level of classification. The evidence supporting this claim was discussed by the Committee who concluded that this argument could also be applied to consideration of reclassification of a 20 mg dose of omeprazole. The Committee noted that omeprazole had been available at a pharmacy-only and general sale level of access in several other countries for a number of years without the emergence of significant safety concerns.

After a period of debate, it was agreed by majority vote (with one member excluded from voting due to a potential conflict of interest) that omeprazole, in tablets containing 20 mg or less of omeprazole, should be reclassified from restricted medicine to pharmacy-only medicine for the short-term, symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and over, when sold in a pack approved by the Minister or the Director-General for distribution as a restricted medicine. However a maximum daily dose of 20 mg of omeprazole in a pack size of up to 14 dosage units should also be specified.

One member wanted it noted that, because these packs would be sold in a pharmacy, it was more appropriate that the warning statements in the New Zealand Regulatory Guidelines should read 'consult a pharmacist or doctor' rather than 'consult a doctor or pharmacist'.

Recommendation

• That omeprazole, in tablets containing 20 mg or less of omeprazole, with a maximum daily dose of 20 mg of omeprazole in a pack size of up to 14 dosage units, should be reclassified from restricted medicine to pharmacy-only medicine for the short-term, symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and over, when sold in a pack approved by the Minister or the Director-General for distribution as a pharmacy-only medicine.
• That Medsafe should update the New Zealand Regulatory Guidelines to reflect this recommendation and to ensure that the warnings statements for omeprazole read 'consult a pharmacist or doctor'.

6.5 Salicylic acid 40%
(The Podiatrists' Board)

Purpose

This was a submission requesting the reclassification of salicylic acid, in packs of medicated plasters or pads containing salicylic acid 40% w/w, from pharmacy-only medicine to restricted medicine for the removal of hard corns.

Background

At the 7^th meeting on 31 July 1990 and 1 August 1990, salicylic acid was reclassified as:

• Part II pharmacy (pharmacy-only); in medicines containing more than 12.5% of salicylic acid
• general sale; in medicines for external use containing not more than 12.5% of salicylic acid.

At the 27^th meeting on 23 May 2002, the Committee recommended that salicylic acid should be classified as a restricted medicine in products containing more than 40% and as a general sale medicine in products containing 40% or less, and Medsafe should be asked to include in the New Zealand Regulatory Guidelines for Medicines a requirement for warnings on the packs against use on moles, on the face or in the genital area. The current submission stated that the labelling for the reclassification should be amended with this recommendation in mind.

At the 36^th meeting on 8 February 2007, the Committee recommended that salicylic acid should be a general sale medicine in preparations for dermal use containing 40% or less and remain a restricted medicine in preparations other than dermal preparations containing 40% or less.

Salicylic is currently classified as:

• restricted; except in medicines for dermal use containing 40% or less
• general sale; in medicines containing 40% or less.

Comments

Two pre-meeting comments were received during the consultation period. One supported the reclassification because they believed the adverse outcomes from inappropriate use reported by the submitter provided a reliable indication of potential harm.

The other did not believe that the current classification of pharmacy-only for Carnation Corn Caps provided in the submission was correct. It was believed that because salicylic acid in this form was for dermal use, and contained 40% or less, then it would be exempt from the restricted medicine classification and default to general sale.

Discussion

The Committee were pleased that the healthcare sector was engaging in the process and a submission for reclassification had been made.

The submission was not supported. The products were widely used and the concerns raised in the submission were solely based on two case reports. In addition, the Committee considered there was a clear consumer advantage to self-selection of these products.

One member of the Committee suggested there was potential for an article in Prescriber Update on these adverse reactions.

The classification of salicylic acid in New Zealand was currently harmonised with Australia. The Chair reminded the Committee that the principle of harmonisation used by both New Zealand and Australia was that 'the least restrictive classification should usually be adopted unless there was a strong public health issue'. It was agreed that the presentation of two case studies was not sufficient evidence of a public health risk to warrant changing the currently harmonised classification statements.

Recommendation

That salicylic acid, in packs of medicated plasters or pads containing salicylic acid 40% w/w, should not be reclassified from pharmacy-only medicine to restricted medicine for the removal of hard corns.

7 NEW MEDICINES FOR CLASSIFICATION

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

7.1 Canakinumab (Ilaris 150 mg powder for injection)

Canakinumab is a high-affinity fully human anti-human-IL-1β monoclonal antibody that belongs to the IgG1/к isotype subclass. It is expressed in a murine SP2/0 cell line.

Ilaris is a sterile, white, lyophilised powder that is reconstituted with water for injections and administered as a subcutaneous injection. A reconstituted single-use vial delivers 150 mg canakinumab per 1 mL.

Ilaris is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes, in adults and children aged four years and older including:

• Familial Cold Autoinflammatory Syndrome / Familial Cold Urticaria
• Muckle-Wells Syndrome
• Neonatal-Onset Multisystem Inflammatory Disease / Chronic Infantile Neurological, Cutaneous Articular Syndrome.

Recommendation

That canakinumab should be classified as a prescription medicine.

7.2 Clofarabine (Evoltra 20 mg / 20 mL concentrate for injection)

Clofarabine is a purine nucleoside antimetabolite structurally related to marketed substances like fludarabine and cladribine. It is a white to off-white solid which is soluble in saline up to 1.5 mg/mL at room temperature. The optical rotation is + 39.93 degrees (average; c = 5 mg/mL, 25 degrees centigrade) in dimethylformamide solvent. The alcohol pKa is 16, the amine pKa is 12, and the protonated base pKa is approximately two.

Evoltra is a sterile, clear, practically colourless solution containing clofarabine 20 mg / mL. Each 20 mL vial contains 20 mg of clofarabine and 180 mg of sodium chloride. This is equivalent to 3.08 mmol (or 70.77 mg) of sodium and should be taken into consideration for patients on a controlled sodium diet. The solution also contains Water for Injections. The pH of the solution ranges between 4.5 and 7.5 and it has an osmolarity of 270 to 310 mOsm/L.

Evoltra is indicated for the treatment of acute lymphoblastic leukaemia in paediatric patients who have relapsed or are refractory after receiving at least two prior regimes. This use is based on the induction of complete responses.

In Australia, the Standard for the Uniform Scheduling of Drugs and Poisons defined clofarabine as a prescription medicine.

Recommendation

That clofarabine should be classified as prescription medicine.

7.3 Fampridine (10 mg modified release tablet)

Fampridine modified release tablet is a potassium channel blocker, available in a 10 mg tablet strength. Each tablet contains 10 mg fampridine, formulated as a prolonged release tablet for twice-daily oral administration. Each fampridine 10 mg modified release tablet also contains hypromellose, cellulose-microcrystalline, silicon dioxide, magnesium stearate and the film coat (Opadry white) contains hypromellose, titanium dioxide and polyethylene glycol.

Fampridine 10 mg prolonged release tablets are indicated for the treatment of patients with Multiple Sclerosis for the improvement of walking ability.

In Australia, the Standard for the Uniform Scheduling of Drugs and Poisons defined fampridine under 4-aminopyridine as a prescription medicine for therapeutic use.

Recommendation

That fampridine should be classified as a prescription medicine.

7.4 Isopropyl Myristate (Full Marks topical solution, 50% w/w isopropyl myristate)

Medsafe had received a New Medicine Application for Full Marks, a medicine indicated for the control of head lice that contains isopropyl myristate, a fatty-acid ester, as the active ingredient. This is incorporated as a 50% w/w solution in cyclomethicone-D5, a cyclic siloxane solvent and is intended for direct topical application to the scalp.

The Committee noted that isopropyl myristate is an established excipient in approved medicines and widely used in cosmetics and as a food additive. However, there were no currently approved medicines in New Zealand that included this as the active ingredient for such use. Consequently, it was 'an innovative new medicine' according to Medsafe policy. The product had already been approved in the United Kingdom and Australia for the control of head lice.

It was also noted that a classification decision for this substance had the potential to affect all products that contained isopropyl myristate, and not just those with therapeutic claims. Isopropyl myristate had been assessed for its suitability for use in cosmetics in the United States and United Kingdom. Classifying isopropyl myristate under the Medicines Act 1981 would make it a medicine. Safety and toxicology data had been included in the New Medicine Application and there was no evidence of harm when isopropyl myristate was used an excipient.

The Committee agreed that the toxicology and safety data available did not raise cause for concern and as such isopropyl myristate should not be added be added to the First Schedule of the Medicines Regulations 1984.

Recommendation

That isopropyl myristate should not be added be added to the First Schedule of the Medicines Regulations 1984.

8 HARMONISATION OF NEW ZEALAND AND AUSTRALIAN SCHEDULES

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

8.1.1 Certolizumab pegol

Certolizumab pegol is a pegylated tumour necrosis factor inhibitor (specifically TNF-alpha), which results in an interference in the production of downstream inflammatory mediators, including interleukin-1, prostaglandins, platelet activating factor, and nitric oxide.

Certolizumab pegol is indicated for the treatment of adults with moderate to severe active rheumatoid arthritis. It is also used in maintaining clinical response and reducing signs and symptoms of moderate to severe Crohn's disease in adults who had inadequate response to conventional therapy. Certolizumab pegol is also under investigation in the treatment of psoriasis.

It was decided at the 58^th meeting in February 2010 to include certolizumab pegol in Schedule 4 (prescription medicine) of the Standard for the Uniform Scheduling of Medicines and Poisons. It was agreed that the involvement of a medical practitioner was required for the supply of certolizumab pegol.

Recommendation

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

8.2 Recommendations made by the National Drugs and Poisons Schedule Committee (NDPSC) to the MCC

8.2.1 57th Meeting on 20-21 October 2009

The Committee noted that, following the 57^th meeting, the Australian National Drugs and Poisons Schedule Committee did not harmonise with New Zealand regarding:

1. guaiphenesin - remained a Schedule 4 (prescription medicine) entry
2. zolmitriptan - remained a Schedule 4 (prescription medicine) entry
3. benzocaine - the item was withdrawn prior to the meeting.

a. Magnesium sulfate

The Committee considered whether magnesium sulfate, in divided oral preparations except when containing 1.5 g or less of magnesium sulfate per recommended daily dose, should be added to the New Zealand Schedule as a restricted medicine.

At its 59^th meeting in June 2010, the Australian National Drugs and Poisons Schedule Committee considered a request for an exemption in scheduling for magnesium sulfate in divided preparations containing 15 g or less of magnesium sulfate for use in laxation. However, it was decided that the current scheduling, decided at the 57^th meeting, remained appropriate.

Magnesium sulfate was not currently classified in New Zealand.

No responses had been received from the dietary supplement sector following the Committee's recommendation at the last meeting. Medsafe had written to the peak body of the sector (Natural Products NZ) asking them to inform their members of the Committees' interest in magnesium sulfate.

It was noted that in New Zealand there were no medicines that contained magnesium sulfate in divided oral presentations. In addition there were no reports of adverse reactions for magnesium sulfate preparations despite their widespread availability. One member also suggested the issue that led to magnesium sulfate being in front of the National Drugs and Poisons Schedule Committee was not relevant to New Zealand. The Australian consideration had arisen from the sale of divided doses of magnesium sulfate for use as a colon cleansing agent. The Committee concluded there was insufficient evidence of harm in New Zealand to warrant a change in classification and, in keeping with the principles of harmonisation, did not support moving away form the current general sale classification.

Recommendation

That magnesium sulfate, in divided oral preparations except when containing 1.5 g or less of magnesium sulfate per recommended daily dose, should not be added to the New Zealand Schedule as a restricted medicine.

b. Red yeast rice

The classification of red yeast rice, which contains 10 mg/kg or more of lovastatin (monacolin K), as a prescription medicine was considered now that the natural healthcare products sector had been given the opportunity to submit information on the effect of the proposal on products containing red yeast rice.

Medsafe had written to the peak body of the sector (Natural Products NZ) asking them to inform their members of the Committees' interest in red yeast rice. One response had been received which did not mention the effect in New Zealand of the proposal but did provide a bibliography of studies published internationally. The Committee were provided with a review of the articles listed in the bibliography which concluded:

1. the articles referenced in the bibliography did not inform on the effect of the proposal on products containing red yeast rice
2. no information was provided that would support an objection to the classification of red yeast rice containing 10 mg/kg or more of lovastatin as a prescription medicine
3. no information was provided that would support an objection to the classification of any other product, including oyster mushroom, containing 10 mg/kg or more of lovastatin as a prescription medicine
4. no information was provided that would support an objection to the scheduling of all HMG-CoA reductase inhibitors, including lovastatin, as a class entry.

The review noted that the articles considered were small scale studies but were sufficient to support the hypothesis that red yeast rice extracts may produce a therapeutic affect and produce adverse effects similar to those seen for lovastatin, the active component of red yeast rice. Larger scale studies would be required to confirm these results as reliable, however the data provided was considered to be sufficient to support harmonisation with the Australian classification decision.

The Committee also noted a Best Evidence Interview in Cardiology, entitled 'Using red yeast rice to lower cholesterol in patients intolerant to statins'. The subject of the interview was a study into the tolerability of red yeast rice (2,4000 mg twice daily) versus pravastatin (20 mg twice daily) in patients with previous statin intolerance. After 12 weeks, both treatments were associated with a low incidence of treatment discontinuation due to myalgia, no evidence of muscle weakness and a similar level of low-density lipoprotein cholesterol. However, the results could not be extrapolated to other red yeast rice formulations and no inference about the long-term effects of this product on cardiovascular morbidity or mortality could be drawn from the study.

One member tabled an article from Medscape, 'Statin levels vary wildly in red yeast rice'.

Scheduling red yeast rice, monacolin K and / or lovastatin was discussed at length. The question arose as to whether red yeast rice, which contains more than one active ingredient, or just monacolin K and / or lovastatin be scheduled. There was evidence that several natural products contain doses of lovastatin equivalent to those obtainable from pharmaceutical products. Red yeast production was variable and non-pharmacologically active products, e.g. foodstuffs, should not be inadvertently captured by any classification. While monacolin K was a naturally occurring substance, it was structurally identical to lovastatin and there were reports of adverse effects associated with red yeast rice products.

The Committee agreed that, given the articles presented, there was sufficient evidence to warrant both lovastatin and monacolin K being classified as prescription medicines. However, given that monacolin K is also present in foodstuffs, the wording of the Schedule entry for monacolin K should use the approach taken by Medsafe when classifying Phosphodiesterase type 5 inhibitors, i.e. prescription; except when present as an unmodified, naturally occurring substance; except when specified elsewhere in this Schedule. The recommendations would partially harmonise New Zealand with Australia.

Recommendation

• That lovastatin should be added to the New Zealand Schedule as a prescription medicine.
• That monacolin K should be added to the New Zealand Schedule as a prescription medicine.
• That Medsafe should consider the wording of monacolin K as a prescription medicine so that any foodstuffs would not be inadvertently captured.

Secretary’s note
A valid objection has been received regarding the above recommendations.

See the addendum to these minutes (at the top of this page) for further details.

8.2.2 58^th Meeting on 16-17 February 2010

The Committee noted that, following the 58^th meeting, the Australian National Drugs and Poisons Schedule Committee did not harmonise with New Zealand regarding:

1. famciclovir
2. fexofenadine.

a. Flurbiprofen

Flurbiprofen products currently available in Australia include lozenges for the treatment of sore throats (Schedule 2 / pharmacy-only medicines) and eye drops for the treatment of intraoperative miosis (Schedule 4 / prescription medicines). The National Drugs and Poisons Schedule Committee considered an application that requested an exemption from scheduling when for topical oral use. This application was the same as the submission discussed during Agenda Item 5.2 and the concerns expressed by the Committee were the same in this harmonisation discussion.

The National Drugs and Poisons Schedule Committee decided:

• that divided preparations for topical oral use containing 10 mg or less per dosage unit remained appropriately scheduled in Schedule 2 (pharmacy-only medicine)
• to broaden the Schedule 2 (pharmacy-only) flurbiprofen entry to include undivided preparations containing 0.25% or less or 10 mg or less per dose of flurbiprofen.

This decision was confirmed at their 59^th meeting in June 2010.

One pre-meeting comment had been received during the consultation period which supported the decision of the National Drugs and Poisons Schedule Committee.

In New Zealand, flurbiprofen is classified as:

• prescription; except in throat lozenges containing 10 mg or less per lozenge
• pharmacy-only; in throat lozenges containing 10 mg or less per lozenge.

The Committee agreed that New Zealand should harmonise with Australia and discussed the terminology that would allow harmonisation because undivided preparations had been included in their Schedule 2 (pharmacy-only) entry. Harmonising would align flurbiprofen with other non-steroidal anti-inflammatory medicines.

Safety issues were not well defined for sprays and mouthwashes as they had been with other oral liquid dose forms. However, it was noted that the risk of anaphylaxis existed for all dose forms.

Following discussion it was agreed that 'locally acting oromucosal preparations' would include lozenges as well as liquids and other methods of oral administration. Updating the pharmacy-only entry in the New Zealand Schedule would have implications for the prescription medicine entry. This entry would also need updating.

Recommendation

That New Zealand should harmonise with Australia by amending the pharmacy-only medicine entry of flurbiprofen to include 'locally acting oromucosal preparations'.

b. Nicotine

The first-line pharmacological intervention for nicotine dependence from cigarette smoking is nicotine replacement therapy for reducing the cravings associated with smoking cessation - available as chewing gum, transdermal patches, inhalers, nasal sprays, sublingual tablets, and lozenges.

The National Drugs and Poisons Schedule Committee decided to amend the scheduling of nicotine to exempt oromucosal spray use, as an aid in withdrawal from tobacco smoking, from scheduling.

The Committee considered this harmonisation alongside agenda item 6.3 and had agreed to harmonise.

Recommendation

That New Zealand should harmonise with Australia by amending the general sale classification of nicotine from 'for transdermal use in chewing gum, lozenges or sublingual tablets' to 'for preparations for oromucosal or transdermal absorption'.

c. Paracetamol combined with phenylephrine and guaiphenesin

The National Drugs and Poisons Schedule Committee decided to extend their current exemption for certain paracetamol plus phenylephrine combination products to also include combinations containing guaiphenesin. In summary, in Australia, paracetamol is exempt from scheduling under the following conditions:

• 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 enclosed in a pack that contains not more than 12 such powders or sachets
• 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 packed in a blister or strip packaging or in a container with a child resistant case and when in a pack containing not more than 25 tablets or capsules.

There are also labelling requirements attached to these conditions.

The New Zealand Schedule does not limit paracetamol combined with other active ingredients so in this respect harmonisation was not relevant. New Zealand already allows for combinations of paracetamol as general sale medicines with other active ingredients classified as general sale.

However, because paracetamol has a higher maximum pack size cut-off for general sale medicines in Australia, this could result in differences in a product's classification between the two countries. The Committee considered harmonising with Australia on the maximum pack size for paracetamol as a general sale medicine as a separate issue in Agenda Item 8.3.2.

Two pre-meeting comments had been received during the consultation period. Neither supported the harmonisation because of recently highlighted safety concerns, even if it meant continuing to be different from Australia.

Recommendation

No recommendation was required.

8.3 Other harmonisation issues

8.3.1 Benzocaine

In Australia, benzocaine is classified as a:

• Prescription medicine, except:
  1. when listed in Schedule 2 (pharmacy-only medicine)
  2. in dermal preparations containing 2% or less of total anaesthetic substances, or
  3. in lozenges containing 30 mg or less of total anaesthetic substances per dosage unit.
• Pharmacy-only medicine in preparations for topical use other than eye drops:
  1. containing 10% or less of total anaesthetic substances, except in dermal preparations containing 2% or less of total local anaesthetic substances, or
  2. in divided preparations containing 200 mg or less of total local anaesthetic substances per dose unit, except in lozenges containing 30 mg or less of local anaesthetic substances per dosage unit.

In New Zealand, benzocaine is classified as:

• prescription; for internal use; for external use in medicines containing more than 10% of total local anaesthetic substances
• pharmacy-only; in mouthwashes containing 10% or less of total local anaesthetic substances; for external use in medicines other than mouthwashes containing 10% or less and more than 2% of total local anaesthetic substances except in throat lozenges containing 30 mg or less of total local anaesthetic substances per dose unit
• general sale; for external use in medicines containing 2% or less; in throat lozenges containing 30 mg or less per dose form.

The Committee considered harmonising with the classification of benzocaine now that further information had been provided confirming there were products approved in Australia using benzocaine as an appetite control. The local anaesthetics present anaesthetise the stomach and suppress hunger.

The item was withdrawn prior to the 57^th meeting of the National Drugs and Poisons Schedule Committee in October 2009.

The Committee noted that although New Zealand did not currently have any products that would be affected by this change in classification, there were sufficient safety issues associated with the ingestion of high doses of benzocaine to warrant harmonisation of the Schedule entries.

Recommendation

That New Zealand should harmonise with Australia on the classification of benzocaine.

8.3.2 Paracetamol

At the 26^th meeting on 11 December 2001, the Committee recommended that:

• New Zealand should increase the maximum pack size for sale of paracetamol as a general sale medicine from 10 g to 12.5 g in order to harmonise with the less restrictive Australian classification
• the increase should take place only after the Committee had approved revised labelling requirements which were acceptable to both New Zealand and Australia
• labels should include a warning with specific reference to liver failure
• Medsafe should persevere with its intention to encourage grocery organisations to consider developing codes for the sale of medicines such as aspirin and paracetamol.

It had been brought to Medsafe's attention that these recommendations had not been progressed because the joint agency between New Zealand and Australia had not been established. The Committee reconsidered the maximum pack size for paracetamol as a general sale medicine.

Pack sizes of products containing paracetamol had been discussed, but no recommendations had been made, at the 1^st meeting on 13 November 1984, 2^nd meeting on 19 March 1985 and 5^th meeting on 11 November 1986.

At the 6^th meeting on 10 March 1987 the Committee recommended a limit of 10 g per pack for paracetamol.

Discussions continued at the 15^th meeting on 30 November 1995, 16^th meeting on 24 April 1996, 17^th meeting on 15 May 1997, 18^th meeting on 15 October 1997, 20^th meeting on 19 November 1998 and the 27^th meeting on 23 May 2002.

Three pre-meeting comments had been received during the consultation period. One submission supported harmonised pack sizes and provided a review that the change in pack size would unlikely alter the safety profile of paracetamol in New Zealand. The review focussed on the:

1. changes in pack size, availability and labelling in the United Kingdom and Australia
2. risk of hepatotoxicity with paracetamol overdose
3. effect of pack size on overdose rates and risk of hepatotoxicity
4. differences in purchasing patterns of paracetamol or suicide rates in New Zealand and Australia.

However, two submissions did not support any increase in the maximum permitted pack size of paracetamol as a general sale medicine. The Committee noted an article, provided with one of the submissions, in the Wairarapa Times Age newspaper (30 August 2010) which described a District Health Board initiative to encourage dairies, supermarkets and pharmacies to sign a voluntary code limiting the amount of paracetamol sold in order to lower the region's suicide rate from deliberate overdose.

One member suggested that the risk of harmonising to a pack size of 12.5 g could be managed by labelling. Although this suggestion was not accepted by other members, it was agreed that Medsafe should discuss harmonising the labelling of paracetamol.

The Chair reminded the Committee that they needed to think about the public health risk and whether it was sufficient enough not to harmonise. In the Committee's opinion access to bigger packs would increase the accessibility of paracetamol for intentional overdose. If an overdose occurred, bigger packs would increase the risk of significant harm to the individual when they overdose due to the larger amount of paracetamol that would be available. The data suggested that risks of harm from overdose increase as pack size increases above 8 g, and that the need for medical intervention following an overdose increases significantly when pack sizes at or above 12 g were available. The Committee felt that the public health risk associated with increasing the pack size of paracetamol in New Zealand was sufficient enough to overcome the principles of harmonisation.

Recommendation

• That New Zealand should not increase the maximum pack size for sale of paracetamol as a general sale medicine from 10 g to 12.5 g in order to harmonise with the less restrictive Australian classification.
• That Medsafe should consider harmonising with Australia on the labelling of paracetamol.

Secretary’s note
A valid objection has been received regarding the recommendation that New Zealand should not increase the maximum pack size for sale of paracetamol as a general sale medicine from 10 g to 12.5 g in order to harmonise with the less restrictive Australian classification.

See the addendum to these minutes (at the top of this page) for further details.

9 FOR THE NEXT MEETING

Items from this meeting that may be considered at the next meeting were:

1. Vitamin D - colecalciferol (Agenda Item 5.6).
   A number of items were suggested as possible submissions for consideration at the next meeting. Whether or not these would be considered would largely depend on whether submissions for reclassification were received from sponsor companies or other interested bodies.
2. Clobetasone - the discontinuation of Becoderm-C has left consumers without an over-the-counter clobetasone butyrate 0.05% topical preparation option. A solution could be removing the wording, 'which have received the consent of the Minister or Director-General to their distribution as restricted medicines and are sold in the manufacturer's original pack', from the restricted medicine classification statement.
3. Influenza vaccine - access for pharmacists.
4. Naproxen - currently classified as a pharmacy-only medicine in solid dose form containing 250 mg or less per dose form in packs of not more than 30 tablets or capsules. The indications are not limited so there could be a risk which would warrant more restrictive scheduling. However, evidence of actual harm would be required in a submission.

10 GENERAL BUSINESS 10.1

Scheduling of medicines in Australia

The Committee noted that from 1 July 2010, the National Drugs and Poisons Schedule Committee had been replaced by the Secretary of the Department of Health and Ageing, or her delegate, as the decision maker for the scheduling of medicines and chemicals in Australia. Two new expert advisory committees, the Advisory Committee on Medicines Scheduling and the Advisory Committee on Chemicals Scheduling, had been established to provide advice and to make recommendations to the Secretary (or her delegate) on medicines and chemicals scheduling decisions.

A representative from Medsafe would be an observer on the Advisory Committee on Medicines Scheduling.

11 DATE OF NEXT MEETING

To take place on a Tuesday in April or May 2011. 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 2:20pm.