Revised: 23 May 2013

Committees

Minutes of the 38th meeting of the Medicines Classification Committee - 14 December 2007

Medsafe agrees with all but one of the recommendations made at the 38th meeting. Medsafe does not agree with part of the recommendation relating to agenda item 5.2.4 on the labelling of glucosamine complexed products containing potassium and has submitted an alternative recommendation asking that the matter be returned to the agenda of the next meeting in order to find a more feasible way to implement the Committee's recommendation. The Minister's Delegate has accepted Medsafe's alternative advice.

Held in the Medsafe Boardroom, Level 6, Deloitte House, 10 Brandon Street, Wellington. Commencing at 9:30AM.

PRESENT

Dr S Jessamine (Chair)
Mrs A Shirtcliffe
Ms N Gauld
Dr J Peckham
Dr T Healy
Mrs C Smith (Secretary)

1. Welcome

Dr Jessamine welcomed members to the 38th meeting. He also welcomed an American pharmacy student as an observer for part of the meeting.

2. Apologies

An apology was received from Dr David Galler. Dr Galler had prepared comments on agenda items and these were distributed to Committee members.

3 CONFIRMATION OF THE MINUTES OF THE 37TH mEETING

The minutes of the 37th meeting were accepted as an accurate record of the meeting and were signed by the Chairman.

4. Declaration of conflicts of interest

One of the members had declared several interests which might be considered to pose a conflict. These were discussed in the presence of the member and were considered not to present any relevant conflict with items on the current agenda.

5 matters arising

5.1 Objections to recommendations made at the 37th meeting

 5.1.1 Polysulfated glycosaminoglycans

An objection had been received from Alcon indicating that the recommended generic schedule entry for polysulfated glycosaminoglycans as prescription medicines when for injection inadvertently captured intraocular viscoelastic products. It was noted that intraocular viscoelastic products were exempt from scheduling under Appendix A in the Australian schedule and they had been reclassified to general sale medicines in New Zealand in order to harmonise with the Australian exemption.

The issue of whether or not to include polysulfated glycosaminoglycans in the New Zealand schedule had previously been discussed by the Committee in May 2002. At that meeting the Committee had declined the recommendation to add polysulfated glycosaminoglycans to the schedule as prescription medicines on the grounds that it was unclear as to which medicines the term would apply and that any medicines which were polysulfated glycosaminoglycans would be scheduled according to their individual names.

The 2002 recommendation did not restrict the prescription medicine schedule entry to injectable medicines only.

Members discussed difficulties relating to the identification of these substances and agreed that, in order to harmonise with the Australian position as agreed at the previous meeting, it would be necessary to adopt wording into the New Zealand schedule which would differ from that in the Australian schedule in that intraocular viscoelastic products would need to be specifically exempted from the prescription schedule entry. This would result in an "essentially" harmonised position for any products containing polysulfated glycosaminoglycans. The entry should control the possible use of injectable polysulfated glycosaminoglycans by unqualified medical practitioners for cosmetic purposes but allow intraocular viscoelastic products to remain as unscheduled medicines in order to harmonise with the Appendix A exemption for intraocular viscoelastic products in the Australian schedule.

Recommendation

That polysulfated glycosaminoglycans should be classified as prescription medicines when for injection except when contained in intraocular viscoelastic products.

5.1.2 Sedating antihistamines in children under 2 years of age

An objection had been received from Schering Plough to the earlier recommendation for all sedating antihistamines to be prescription medicines for children under two years of age. As this recommendation had been made the previous year and no further recommendation had been made at the 37th meeting, the objection per se was not considered to be valid. However, the MCC had indicated that it was interested in considering any new safety data on this subject which the company was able to produce.

Since the previous meeting two different expert committees of the Food and Drug Administration (FDA) in the United States, the Non-Prescription Drugs Advisory Committee and the Pediatric Advisory Committee, had jointly considered a petition to the FDA to contra-indicate cough and cold medicines, including sedating antihistamines, for use in children under six years of age. The petition and the background papers for this meeting had been made available to the MCC through the FDA website.

Medsafe had prepared a report for the Medicines Adverse Reactions Committee (MARC) which reviewed the briefing documents prepared by the FDA for their expert advisory committees' review of the safety and efficacy of cough and cold medicines available for use in children. The MARC had considered this matter the previous day and recommendations from this committee could be expected in due course. The Medsafe report was also made available to the MCC.

The Medsafe report concluded that:

• There were little efficacy data available for children up to 16 -18 years of age. Most efficacy data were for adult doses.
• Efficacy and doses for children had been largely extrapolated from adult data. It was now known that these medicines did not necessarily work the same way in small children
• There had been deaths reported (in New Zealand)* in the under-two age group and some of these deaths had occurred at normal doses.
• There did not yet appear to be sufficient evidence to contraindicate these medicines in children over two years of age. It appeared from the petition to the FDA that a high percentage of the childhood deaths occurred in children under two while the remainder occurred in children under six years of age.

The Committee agreed that if there was little or no benefit to be gained from a medicine, then any risk was pertinent. Members therefore felt that other cough and cold medicines including pseudoephedrine should also be considered with a view to reclassification to prescription medicines when for use in children under two. The matter should be added to the agenda of the 39th meeting.

Consideration of whether or not these products should be contraindicated in children under six years of age should wait until the FDA had made a decision about this age group.

There was some discussion on the appropriate level of access to these medicines. It was agreed that doctors did not usually prescribe cough and cold medicines for young children and did not know what doses were suitable in this age group. Nor was there evidence to suggest that pharmacists had access to such information. Therefore, reclassifying to restricted medicine would be of little benefit.

Accidental overdose due to use of multiple products was acknowledged as being an important element in childhood poisonings as families often had several products in their homes. Education was seen to be a key element in the avoidance of accidental overdosing and the Committee agreed that all sedating antihistamine products should carry a pack warning reminding parents not to use other cough and cold preparations at the same time. Medsafe should also be asked to review the labelling of all combination packs to ensure that the products were contraindicated in children under the age of two and did not carry dose instructions for this age group.

It was agreed that information for prescribers would be helpful and that Medsafe should be asked to publish an article in Prescriber Update about use of sedating antihistamines in young children.

Use of all other cough and cold preparations should be put on the agenda for the next meeting with a view to reclassification to prescription medicine when for children under two years of age.

Recommendation

• 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
• That Medsafe should be asked to write an article for Prescriber Update informing doctors about the use of sedating antihistamines and other cough and cold preparations in children under two years of age
• That future applications for consent to market sedating antihistamines and cough and cold products for children should be based on safety data obtained from proper studies conducted on children in the relevant age group.

* Correction
Deaths from use of cough and cold medicines in children under two years of age, as referred to in the Medsafe report, did not occur in New Zealand. There have been no reported deaths in New Zealand from use of these medicines in children under two years of age.

5.2 Other matters arising from the 37^th meeting

5.2.1 Exemption to allow optometrists to sell certain pharmacy-only medicines

At the previous meeting the New Zealand Association of Optometrists (NZAO) had applied for exemption from pharmacy-only status for a number of pharmacy-only eye products to allow them to be sold from optometry practices. The medicines for which the NZAO had requested the exemption were:

Antazoline
Levocabastine
Lodoxamide
Naphazoline
Oxymetazoline
Pheniramine
Propamidine and dibromopropamidine.
Sodium cromoglycate
Tetrahydrazoline
Xylometazoline

Members had already agreed that sale by registered optometrists would be acceptable, but had had concerns about other staff being sufficiently well-trained to deal with such sales. They had therefore recommended against an exemption from pharmacy-only status to allow sale from optometry practices. However, they agreed that, as an interim measure pending the establishment of training and accreditation for optometry assistants, they would be happy for optometrists to be able to sell the products as part of a consultation.

The NZAO had agreed that training and accreditation of optometry assistants was still some way off and that the intention of the submission had been for sales to be made only by a registered optometrist during the course of a consultation. The NZAO confirmed that products would be stored in examination rooms and would not be available for self-selection by customers.

The Committee agreed that this arrangement would be acceptable. There was some discussion about how the exemption would be monitored and about the development of a code of practice for the appropriate storage, use and sale of these medicines. However members agreed that it was up to the regulating body to undertake these activities. Provided the regulating body had been appropriately informed, the Committee agreed to recommend the exemption from pharmacy-only status for the medicines concerned.

Recommendation

That the following medicines should be exempt from pharmacy-only status when used or sold in practice by a registered optometrist:

• Antazoline
• Levocabastine
• Lodoxamide
• Naphazoline
• Oxymetazoline
• Pheniramine
• Propamidine and dibromopropamidine.
• Sodium cromoglycate
• Tetrahydrazoline
• Xylometazoline

5.2.2 Nicotinic acid

The NDPSC had recommended that New Zealand should harmonise with the 250 milligram cut-off point between restricted medicine and prescription medicine.

The current classification of nicotinic acid in New Zealand was restricted medicine in medicines containing more than 100 milligrams per dose form and general sale in medicines containing 100 milligrams or less per dose form.

The current classification of nicotinic acid in Australia was:

• Prescription/S4: in medicines containing more than 250 milligrams per dose form
• Restricted/S3: in medicines containing 250 milligrams or less and more than 100 milligrams
• Unscheduled: in medicines containing 100 milligrams or less per dose form

The recent exemption for nicotinamide was intended to remain in effect.

The proposed change would cause one restricted medicine containing 500 milligrams of nicotinic acid to become a prescription medicine.

Members agreed to adopt the Australian dose levels. In order to accommodate external medicines containing nicotinic acid, the cut-offs should be expressed as "per dose" rather than as "per dose unit".

Recommendation

That nicotinic acid, excluding nicotinamide, should be classified as:

• Prescription medicine in medicines containing more than 250 milligrams per dose
• Restricted medicine in medicines containing 250 milligrams or less but more than 100 milligrams per dose
• General sale medicine in medicines containing 100 milligrams or less per dose

5.2.3 Aspirin in compound products

At the 37^th meeting no recommendation had been made about whether or not New Zealand should harmonise with the Australian prescription medicine scheduling of aspirin when compounded with caffeine, paracetamol or salicylamide. A decision had been postponed pending further information about the safety of these compound products.

It had been noted at the 37th meeting that only one product on the New Zealand market fell into this category and requested that the Secretary approached the sponsor company to seek any safety data the company might have about the product and what impact a reclassification to prescription status would have on the viability of the product. In response, the company had stated that it was intending to withdraw the product from the New Zealand market.

In view of the fact that harmonisation with the Australian classification would no longer have an impact on any current products on the New Zealand market, the Committee agreed that aspirin should become a prescription medicine when in combination with caffeine, paracetamol or salicylamide.

Recommendation

That aspirin should be classified as a prescription medicine when in combination with caffeine, paracetamol or salicylamide.

5.2.4 Potassium in glucosamine sulfate complexed products

Before making a recommendation at the previous meeting about whether or not to harmonise with the Australian scheduling of potassium the Committee had requested that information should be sought about the potassium content of glucosamine sulfate complexed products on the New Zealand market in order to avoid capturing glucosamine products under the schedule entries for potassium. A number of responses had been received from sponsor companies of complementary medicines and dietary supplements containing glucosamine.

Members had noted at the previous meeting that the reason for classifying potassium chloride separately and more restrictively in Australia was probably not as valid in New Zealand due to cooler climatic conditions.

With regard to opting to differ in New Zealand over the classification of potassium it was noted that Australia was able to impose labelling statements on complementary medicines whereas New Zealand legislation did not allow for this. Dr Jessamine informed the Committee that the Dietary Supplements Regulations were currently under review. The intention was to divide dietary supplements into food-type and therapeutic-type supplements. It was proposed that the therapeutic-type supplements would then come under the control of Medsafe.

The Committee noted that use of glucosamine was growing and it was perceived as a safe product in that it was natural. It was not always possible to ascertain the potassium content of glucosamine products in complementary medicines. It would be unlikely that average consumers would realise that such products could contain significant amounts of potassium. In addition, consumers might unknowingly eat foods containing high levels of potassium.

The committee also noted that it was possible that there were already glucosamine products on the market containing sufficient potassium to mean that, technically, they would qualify as pharmacy-only medicines.

There was some concern about use of glucosamine sulfate complexed products in cases of acute renal failure but members agreed that this condition would probably be picked up quite quickly. Of greater concern was use by those with intermediate renal failure. While the condition would probably be monitored regularly by a doctor, the doctor might not know to ask about possible complementary products taken by the patient. There was general agreement that Medsafe should be asked to prepare an article for Prescriber Update pointing out to doctors that glucosamine products may be a significant source of potassium.

Discussion followed about whether or not glucosamine sulfate complexed products should contain warning statements and about the nature of any such statement. Members concluded that a statement of the amount of potassium contained in each dose should be added to the packs of glucosamine sulfate complexed products containing potassium. In addition, glucosamine sulfate complexed products containing potassium should carry a warning on the pack that the product should not be used by consumers with kidney problems. Complementary medicine glucosamine products which were currently general sale products would default to pharmacy-only medicines unless these two requirements were met.

It was agreed that the current cut-off point between general sale and pharmacy-only medicine for oral products containing potassium should remain at 100 milligrams of elemental potassium per recommended dose. The current exceptions for oral rehydration therapy, parenteral nutrition replacement or dialysis products should remain.

The complementary medicines sector and the pharmacy profession should be informed of these requirements for glucosamine sulfate complexed products containing potassium.

The NDPSC should be informed of the MCC decision not to harmonise on the classification of potassium and potassium chloride.

Recommendation

• That potassium should be classified as a pharmacy-only medicine when for internal use:
  • in slow release or enteric coated forms
  • in medicines containing more than 100 milligrams per recommended dose
  • in glucosamine sulfate complexed products containing more than 100 milligrams of elemental potassium per recommended dose except when carrying a label warning against use with kidney problems and a statement of the potassium content per dose
  • except in medicines for oral rehydration therapy, parenteral nutrition replacement or dialysis
• That potassium should be a general sale medicine when:
  • for external use
  • for internal use in medicines containing 100 milligrams or less per recommended dose
  • in glucosamine sulfate complexed products containing more than 100 milligrams of elemental potassium per recommended dose when carrying a label warning against use with kidney problems and a statement of the potassium content per dose
  • in medicines for oral rehydration therapy, parenteral nutrition replacement or dialysis
• That Medsafe should be asked to write an article for 'Prescriber Update' informing doctors that glucosamine can be a significant source of potassium.

Secretary's note
While Medsafe agrees in principle with the recommendation to require specific labelling statements on glucosamine sulfate complexed products there is no mechanism under the Dietary Supplement Regulations to require warning statements on dietary supplements. The absence of a product register means that it is not possible to identify the products concerned.

Medsafe recommends that a Committee decision about how best to implement its intentions for label statements on glucosamine sulfate complexed products should be postponed until the 39th meeting.

Medsafe Alternative Recommendation

• That a decision on the classification of potassium in glucosamine sulfate complexed products should be referred back to the Committee at the next meeting.
• That Medsafe should be asked to write an article for 'Prescriber Update' informing doctors that glucosamine can be a significant source of potassium.

5.2.5 Mefenamic acid and naproxen

At the 36th meeting in February 2007 the Committee had noted that pharmacy-only packs of ibuprofen and diclofenac contained information on the labels about maximum recommended daily doses. Members had noted that no such dose limits were applicable for mefenamic acid and naproxen and had queried whether, for consistency, all pharmacy-only packs of non-steroidal anti-inflammatory medicines should carry statements about maximum recommended daily doses. The Committee had sought information from sponsor companies of these products about suitable maximum daily doses for their pharmacy-only packs containing these medicines. At the same time, the MCC had also recommended that the NDPSC should explore this matter.

The NDPSC had considered this matter in June 2007 and had concluded that the current scheduling of naproxen and mefenamic acid remained appropriate given that there was no scientific evidence presented requiring a change to the schedule entry and no requirement to pursue consistency for consistency's sake.

In view of the NDPSC conclusion not to require maximum recommended daily dose limits for mefenamic acid and naproxen for consistency with other pharmacy-only non-steroidal anti-inflammatory medicines, the MCC agreed that it would not pursue this matter any further.

No recommendation was required. The NDPSC should be informed of the MCC decision not to require maximum recommended daily dose limits for mefenamic acid and naproxen when sold as pharmacy-only medicines.

5.2.6 Iron pack size limits

Further consideration was given to the NDPSC recommendation that there should be an upper pack size limit of 750 milligrams and a maximum recommended daily dose of 24 milligrams for general sale iron products when in undivided dose forms or in solid dose forms containing more than 5 milligrams per dose form. Oral products which exceeded these limits should be classified as pharmacy-only medicines.

Although a number of cases had been reported to the Poisons Centre over a specified period, of children consuming iron in doses greater than those recommended, the reports did not indicate whether those poisonings had resulted from medicines which had been prescribed or medicines which had been purchased. Of those cases which had been reported only 3 had required medical referral. Members did not feel that limiting the dose size to 5 milligrams for general sale products was justified but agreed that limiting the pack size to 750 milligrams was more relevant. They agreed that general sale packs containing iron should contain a maximum of 750 milligrams and that there should be no restriction on dose sizes. The current recommended maximum daily dose of 24 milligrams should continue to apply as should the exemption from scheduling for all parenteral nutrition replacement preparations.

The NDPSC should be informed of this decision.

Recommendation

That iron should be classified as a general sale medicine when in packs containing not more than 750 milligrams and not more than 24 milligrams per recommended daily dose and in parenteral nutrition replacement preparations.

5.2.7 Ranitidine labelling

At the previous meeting the Committee had considered a company submission for the reclassification of 150 milligram ranitidine tablets from pharmacy-only medicine to general sale medicine when in packs containing no more than 7 days' supply.

While the Committee had been satisfied overall with the safety of the product to justify a change to general sale medicine, there were still some issues to be resolved around pack warning statements.

Members agreed that the company had responded with a vastly improved pack containing all but one of the pack warnings that they had requested. They agreed that it was acceptable for the warning about black stools to be omitted as it was covered in the package insert.

The Committee was impressed with the robust response to its request for improved labelling and agreed that the company should be congratulated on this.

Recommendation

That ranitidine should become a general sale medicine when in packs containing 7 days' supply or less and in tablets or capsules containing not more than 150 milligrams.

5.2.8 Boron

At the previous meeting the Committee had deferred making a recommendation on whether or not to harmonise with Australia on the classification of boron pending information from the complementary medicines and dietary supplements sectors about the current doses and strengths of boron in complementary medicines and dietary supplements in New Zealand.

Several responses had been received and the Committee considered these alongside material which had been provided at earlier meetings.

It appeared from literature that there was a reasonable amount of data available to demonstrate that there were few if any adverse effects observed in doses at the level of 6 milligrams per maximum recommended daily dose sought by the complementary medicines and dietary supplements industry. In addition, information had been provided to demonstrate that dietary boron appeared to assist arthritis and osteoporosis. Populations in areas with low boron levels in food tended to have higher incidence of these conditions whereas areas with high levels of boron tended to have a much lower incidence. This had been demonstrated with data both internationally and from within New Zealand. In addition, it appeared that climate factors affected boron levels in food with levels tending to be higher in dry climates than in wet climates.

It was noted that a recommended daily intake of boron had not yet been established for New Zealand. Internationally, limits ranged from 3 milligrams in Australia to 14 milligrams in the USA. The Expert Working Group on Minerals and Vitamins in the UK had recommended 6 milligrams per day.

The Committee concluded that there were no toxicological issues relating to a daily intake of up to 6 milligrams in dietary supplements and agreed to recommend that this limit should be put into effect using the wording proposed at the 36th meeting. The cut-off point for external use should remain at 0.35%.

At earlier meetings the Committee had also discussed what nomenclature should be used in schedule entries and had proposed that the following should be proposed to the NDPSC for their comments.

"boron, including boric acid and borax". At its June 2007 meeting the NDPSC had endorsed this nomenclature.

Recommendation

• That boron, including boric acid and borax, should be a prescription medicine except when:
  • for internal use in medicines containing 6 milligrams or less per recommended daily dose
  • for dermal use other than paediatric use* in medicines containing 0.35% or less
  • when present as an excipient
• That boron, including boric acid and borax, should be a general sale medicine when:
  • for internal use in medicines containing 6 milligrams or less per recommended daily dose
  • for dermal use other than paediatric* use in medicines containing 0.35% or less
  • when present as an excipient
• That the NDPSC should be informed of the above recommendation.

*Secretary's note
It was necessary to exclude paediatric use from the 0.35% exemption for dermal use in order to maintain the current prevention of the use of such products in young children.

5.2.9 Chloramphenicol eye preparations

At a previous meeting the Committee had agreed that chloramphenicol for eye use should be considered as a suitable candidate for reclassification from prescription medicine to an over-the-counter classification. This change had already occurred in the United Kingdom and documents from the United Kingdom consultation process were provided for members' information. It was noted that there had been no response from any of the sponsor companies of these products.

The pharmacists on the Committee thought that over-the-counter availability of chloramphenicol eye products would rate highly in terms of consumer convenience. They felt that this medicine fulfilled most of the criteria for over-the-counter use. However, there was concern about the potential for improper use. They agreed that good training for pharmacists in the sale of such products was necessary and that the current guidelines for the sale of eye products would need to be improved. One members was aware of a case of loss of sight in the United Kingdom due to use of chloramphenicol by a contact lens wearer. A check list including the need for referral of customers using contact lenses would avoid this problem. Training protocols could be developed jointly with the Pharmacy Guild, the Pharmaceutical Society and the Pharmacy Council. With good pharmacist training and clear guidelines on the sale of these eye products, and good packaging and consumer information, it was thought that chloramphenicol eye products would be suitable for sale as restricted medicines.

There were some reservations about the need for an antibiotic for eye conditions at this level of access. It was pointed out that 60% of eye conditions were viral and self-limiting. Bacterial infections were also usually self-limiting and there were concerns about how pharmacists would distinguish between viral and bacterial infections, particularly in young children. It was noted that pharmacists would not check a child's chest or ears for upper respiratory tract infections. Members agreed that such products should not be used on children under 2 years of age.

There was also concern over resistance issues. While development of resistance to chloramphenicol appeared to be low, sale through pharmacies would be likely to increase usage which in turn could lead to an increase in resistance. It was noted that resistance issues did not appear to have been a problem in the United Kingdom and it was suggested that the information should be sought from the MHRA about resistance issues and whether there had been increased use of these products since they had become available over the counter.

It was also noted that the Australian antibiotic guidelines restricted chloramphenicol to a few indications including the eye and recommended that it should be used only for severe cases.

The Committee concluded that any reservations relating to making chloramphenicol available as a restricted medicine related to diagnosis and possible resistance rather than toxicity. More information should be sought about resistance issues in both New Zealand and abroad, particularly from the MHRA and opinions should be sought from infectious disease specialists and ophthalmologists.

No recommendation would be made at this point.

The matter would be considered again at the next meeting.

6. Submissions for reclassification

6.1.1 Fusidic acid 1% eye drops (Fucithalmic, CSL)

This was a company submission for the reclassification from prescription medicine to restricted medicine of 10 milligrams per gram of fusidic acid in 5 gram tubes.

Because of the value of fusidic acid in the treatment of staphylococcal infections and the development of increasing resistance to fusidic acid, the Committee agreed unanimously that fusidic acid eye drops should not be available over the counter. This criterion was seen to outweigh all other criteria normally considered for reclassification and no further discussion was undertaken.

Recommendation

That there be no change to the current prescription medicine classification of fusidic acid eye drops.

6.1.2 Diclofenac (Voltaren Rapid 12.5mg, Novartis)

This was a company submission for an increase in the permitted pack size for pharmacy-only sale of 12.5 milligram tablets or capsules from 20 dose units to 40 dose units per pack.

The Committee discussed issues relating to larger pack sizes. Members observed that packs of 20 constituted 5 days' supply. This was seen as adequate for short-time use for self-limiting conditions. They were concerned that larger pack sizes could lead to longer periods of use and a trend towards the treatment of chronic conditions particularly among users who were familiar with diclofenac from use on prescription. Maintenance of smaller pack sizes would require more frequent purchase and would increase the chances of advice at the point of sale.

There was also concern about the potential for gastro-intestinal problems, hepatoxicity and interactions with other medicines.

The Committee concluded that an increase in pack size did not meet the criterion for short-term use for over-the-counter medicines. Larger pack sizes could lead to longer term use. This could lead to more adverse effects.

Recommendation

That there should be no change to the pack size limit of 20 dose units for 12.5 milligram diclofenac tablets or capsules when sold as pharmacy-only medicines.

6.1.3 Octocog alpha (Advate, Baxter)

This was a company submission for the reclassification of octocog alpha injections for reclassification from prescription medicine to general sale.

The Committee recognised that all other Factor VIII products had been reclassified as general sale medicines for both ease of access for users and for harmonisation with the Australian exemption for whole blood and blood components under Appendix A of the SUSDP.

There was some discussion about the possibility of confusion of doses for users but members agreed that haemophiliacs were usually fully aware of their doses and that reclassification of this product should not cause problems. Members therefore agreed that octocog alpha should be classified in the same way as all other Factor VIII blood products.

Recommendation

That octocog alpha should be reclassified from prescription medicine to general sale medicine.

6.1.4 Omeprazole 10 mg capsules (Omezol Relief, Pacific)

This was a company submission for the reclassification of omeprazole 10 milligram capsules from prescription medicine to restricted medicine when in packs of 14 capsules for the short-term symptomatic relief of reflux-like symptoms in sufferers aged 18 years and over.

The Committee noted that the above indication as stated in the company submission for reclassification of the product was not the same as that used on the proposed pack. The indication on the proposed pack was "for effective long-lasting relief from heartburn and acid reflux."

Members did not think that the recommended use of up to 14 days was suitable for OTC sale. Nor did they agree with the claim in the submission that the product would provide prompt relief for the stated symptoms. For most consumers the full effect of the product would not be felt for up to four days. Meanwhile, there were a number of other types of products available over the counter which would provide immediate relief. The Committee was of the opinion that if a consumer's symptoms were not relieved by antacids or H2 receptor antagonists then medical investigation was probably required.

The Committee believed that 10 milligram doses were unlikely to be effective and that the product would only work if two capsules were taken. It was thought that the company would need to provide more specific dose instructions on the pack. It was also unclear from the information on the pack as to whether the product should be taken continuously for 14 days or for use as required up to a maximum of 14 days. Information in the submission appeared to be based on use over a 14 day course. This would also require clarification before a classification change could be recommended.

The Committee did not feel that the use of the words "advanced treatment" was appropriate on the pack.

Members noted that there was no information on the proposed pack about interactions with other medicines. Nor was there reference in the submission to a proposed package insert. The Committee expressed a desire to see what warnings were included on the UK pack where omeprazole had been on sale over the counter since 2003. It was suggested that the company be asked to submit copies of the UK package and any associated package insert.

One of the members had investigate sales in the UK and reported that the product had not been selling well over the period since it had been available over the counter. It appeared that a limited number of people used the product due to cost and the availability of funded omeprazole on prescription and, possibly, as the effects were not normally immediate.

The Committee also noted that the company submission contained no details about pharmacist training in the appropriate sale of the product. Although this was not a requirement for reclassification, it was normal practice when prescription medicines were reclassified to restricted medicines for companies to work with pharmacy professional bodies to establish a suitable training package for pharmacies and a protocol for the sale of the product.

One Committee member had consulted with gastroenterologists over possible reclassification and reported that those consulted had not been able to present a strong case against reclassification. It was agreed that a formal opinion should be sought from the Gastroenterology professional body before any recommendation was made to reclassify omeprazole.

While the Committee did not have major concerns about the toxicity of the product or the possibility that sale as a restricted medicine might mask more serious conditions, there were other significant issues still to be resolved. At the current time the members were not willing to recommend that 10 milligram omeprazole capsules should be reclassified as restricted medicines. However, they would be willing to consider a further submission at a later date when the current problems had been addressed.

Recommendation

That there should be no change to the current prescription medicine classification of omeprazole.

6.2 Matters referred by Medsafe

6.2.1 Codeine with paracetamol in C VI controlled drugs

Controlled drugs, including codeine, that fulfill the criteria for medicines in Part VI of the Third Schedule to The Misuse of Drugs Act 1975 are classified under a general entry as pharmacy-only medicines in the medicines schedule. Part VI allows up to 100 milligrams of codeine to be contained in each dose unit of any product in which the codeine is compounded with another ingredient in such a way that the substance cannot be recovered by readily applicable means or in a yield which would constitute a risk to health. There is no restriction on pack size.

Medsafe had noted that codeine levels in pharmacy-only combination products were rising. Previously-approved products contained around 8 milligrams of codeine phosphate per dose form. This had gradually increased to 15 milligrams. Recently an application had been received for a product containing 30 milligrams together with 500 milligrams of paracetamol and in packs of 12 and 96 tablets.

Medsafe had asked that the Committee consider whether it were appropriate for combination products containing 30 milligrams or more of codeine phosphate and in unlimited pack sizes to be available as pharmacy-only medicines. Medsafe had provided some suggested cut-off points and pack size limits for different levels of classification for codeine, taking into account the levels of access in Australia in order to harmonise as closely as was possible for a controlled drug.

The Chairman said that the Committee needed to decide whether there should be more restrictive levels of access to codeine and whether or not pack sizes should be limited.

The Committee noted that codeine abuse for the manufacture of homebake had been high in the 1990s. There had been a decline in the use of homebake with the rise in popularity of methamphetamine. However, since the advent of tighter controls on access to pseudoephedrine, pharmacists had noted a rise in the abuse of codeine.

One of the pharmacists remarked that a change to restricted medicine would have little impact on pharmacists. While the risk would be moved to a different level, there would be little impact on the way sales of codeine were handled in pharmacies. She said that a quick sale of a small pack was often necessary. It was noted that there was a lot of internet information available about which pharmacies carried stocks of certain products.

After some discussion, the Committee agreed that the matter should be discussed again at the next meeting after consultation with interested bodies. Members agreed that;

• pharmacy-only combination medicines containing codeine should be limited to products containing 12 milligrams or less and in packs containing not more than 50 dose units
• Packs containing more than 12 milligrams of codeine but not more than 30 milligrams and in pack sizes of not more than 12 dose units should be restricted medicines.
• Any codeine combination products qualifying as CVI controlled drugs other than those fulfilling the above criteria for pharmacy-only or restricted medicines should be classified as prescription medicines.

These limits would accommodate most of the pharmacy-only codeine products currently on the market.

No recommendation was required at this stage. The matter would be returned to the agenda of the 39th meeting in the first half of 2008.

6.2.2 Zinc

The New Zealand schedule and the Australian SUSDP were already harmonised on the classification of zinc as a general sale medicine in oral preparations containing 25 milligrams or less per recommended daily dose and a prescription medicine in oral preparations containing more than 25 milligrams per recommended daily dose. However, the SUSDP also allowed oral products containing up to 50 milligrams per recommended dose to be unscheduled as long as they bore appropriate warning statements. This meant that it was possible for products containing more than 25 milligrams and up to 50 milligrams per recommended daily dose to be unscheduled products in Australia but prescription medicines in New Zealand.

The proposal was for New Zealand to harmonise as closely as possible on the less restrictive classification.

Supporting data for a new medicine application for an oral product containing more than 25 milligrams but less than 50 milligrams were expected but the company had not been able to supply this information in the required timeframe.

The Committee noted that zinc was claimed to be effective in the prevention of macular degeneration.

The Committee also noted that zinc was available without prescription in Britain in doses of up to 50 milligrams.

Members agreed that products containing up to 50 milligrams should be available as general sale medicines provided those products containing more than 25 milligrams carried a warning statement similar to that required in Australia. They agreed that products in this dose range should carry a warning that the product should not be used for long periods except on medical advice.*

Although this move would appear to harmonise with the Australian scheduling, it was noted that the New Zealand Dietary Supplements Regulations 1985 allowed no more than 15 milligrams per recommended daily dose to be contained in dietary supplements. That meant that, even though zinc in recommended daily doses of up to 50 milligrams would be classified as general sale, any product containing more than 15 milligrams would need to be granted consent to market as a general sale medicine in order to be supplied lawfully, regardless of the requirement for a warning statement on the pack. Products containing more than 15 milligrams of zinc per recommended daily dose which do not have consent to be marketed as general sale medicines would continue to be non-compliant dietary supplements. In effect, this recommendation for reclassification should have no regulatory effect on current compliant dietary supplements.

Recommendation

• That zinc should be classified as a general sale medicine in:
  • medicines containing 25 milligrams or less per recommended daily dose
  • medicines containing 50 milligrams or less and more than 25 milligrams per recommended daily dose when labeled with a statement that the product may be dangerous if taken in large amounts or for long periods or words of similar meaning.

*Secretary's note
Unscheduled zinc products in Australia containing more than 25 milligrams and up to 50 milligrams per recommended daily dose are required to carry one of the following warning statements:
either: May be dangerous if taken in large amounts or for long periods
or: Contains zinc which may be dangerous if taken in large amounts or for long periods

In order to ensure harmonised labelling on both sides of the Tasman, the Chairman has agreed that New Zealand products should carry the same warning statement as required in Australia or words of similar meaning.

6.2.3 Frusemide/ Furosemide

It had been drawn to the attention of the secretary that the recommended International Non-Proprietary Name for frusemide was furosemide and that furosemide was also the BAN and the USAN. Confusion had occurred as some newer products were using recommended International Non-Proprietary Name on their labels. The proposal was for the schedule entry to be amended from frusemide to furosemide. This change was consistent with the trend started in the 1990s to move towards the use of International Non-Proprietary Names as the names of first choice in the schedule.

Since the publication of this agenda the Secretary had become aware of a further example of a name which needed to be updated. This was methotrimeprazine which needed to be updated to the recommended International Non-Proprietary Name, levomepromazine. There was only one product range in the Medsafe database containing this substance and the product was registered using the recommended International Non-Proprietary Name.

The Committee agreed that the schedule entries for both these substances should be amended to the recommended International Non-Proprietary Name and that, in the interest of harmonisation, the NDPSC should be recommended to amend the SUSDP entries for both substances.

Recommendation

• That the prescription medicine entry in the schedule for frusemide should be amended to furosemide
• That the prescription medicine entry in the schedule for methotrimeprazine should be amended to levomepromazine
• That the NDPSC should be asked to harmonise with this nomenclature.

7. New Medicines for classification

The following new chemical entities were referred by the Medicines Assessment Advisory Committee for classification.

Perflutren-containing lipid microspheres. (Definity)

Octafluoropropane and perfluoropropane are synonyms for perflutren.

When used in conjunction with diagnostic ultrasound, Definity provides opacification of the cardiac chambers, improvement in delineation of endocardial borders and assessment of regional myocardial wall motion. Definity provides contrast enhancement in ultrasound studies of the liver and kidney and enhancement of Doppler ultrasound assessment of the vasculature of the liver and kidney.

Definity is indicated for:

• use in patients with contrast-enhanced diagnostic ultrasound imaging to improve characterization of focal lesions of the liver and kidney.
• use in patients with suboptimal echocardiograms to provide opacification of cardiac chambers, improvement of left ventricular endocardial border delineation and assessment of regional wall motion at both rest and stress.

The Committee agreed that perflutren should be a general sale medicine in the same way as other contrast media.

Daptomycin (Cubicin)

Daptomycin is an antibacterial agent of a new class of antibiotics, the cyclic lipopeptides. Daptomycin is a natural product that has clinical utility in the treatment of infections caused by Gram-positive bacteria. Daptomycin retains potency against antibiotic-resistant Gram-positive bacteria, including isolates resistant to methicillin, vancomycin and linezolid.

Daptomycin binds to bacterial membranes and causes a rapid depolarization of membrane potential in both growing and stationary phase cells. This loss of membrane potential causes inhibition of protein, DNA and RNA synthesis. This results in cell death with negligible cell lysis.

Cubicin is indicated for the treatment of complicated skin and skin structure infections (cSSTI) and for Staphylococcus aureus bloodstream infections (bacteremia) (SAB/IE), including right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates in adults. The efficacy of Cubicin in patients with left-sided endocarditis due to Staphylococcus aureus has not been demonstrated.

Cubicin is active against Gram positive bacteria only.

Cubicin is not indicated for the treatment of pneumonia.

The Committee agreed that daptomycin should be classified as a prescription medicine.

Raltegravir (Isentress) tablets.

Raltegravir is an HIV integrase strand transfer inhibitor active against the Human Immunodeficiency Virus (HIV-1). Raltegravir inhibits the catalytic activity of HIV integrase which prevents the covalent insertion, or integration, of the HIV genome into the host cell genome during the early phase of infection. HIV genomes that fail to integrate cannot direct the production of new infectious viral particles, so inhibiting integration prevents propagation of the viral infection.

The proposed indication is Isentress in combination with other antiretroviral agents for the treatment of HIV-1 in treatment experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

The Committee agreed that raltegravir should be classified as a prescription medicine.

Ixabepilone (Ixempra)

Ixabepilone is the first of a novel class of non-taxane, microtubule stabilizing agents called epothilones and their analogs, which have potent activity in chemotherapy resistant tumour models. Ixabepilone is a semi-synthetic analog of epothilone B that stabilizes microtubule dynamics, resulting in blockade of cancer cells during the mitotic stage of the cell division cycle which leads to apoptosis and cell death.

The proposed indications are:

• for the treatment of locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy
• In combination with capecitabine in patients after failure of prior therapy with a taxane and an anthracycline or for whom further anthracycline therapy is not indicated.
• As monotherapy in patients after failure of prior therapy with taxanes, capecitabine and anthracyclines or for whom further anthracycline therapy is not indicated.

Members agreed that ixabepilone should be classified as a prescription medicine.

Laropiprant. (+ nicotinic acid = Cordaptive)

Laropiprant is a potent selective antagonist of the prostaglandin D2 (PGD2) receptor, DP1. Laropiprant suppresses PGD2 mediated flushing associated with administration of niacin.

Niacin at therapeutic levels is a lipid modifying agent.

The Committee agreed that laropiprant should be classified as a prescription medicine.

Alglucosidase alfa-rch (Myozyme)

Alglucosidase alfa-rch is a purified form of the lysosomal enzyme acid alfa-glucosidase. It is produced by recombinant DNA technology in a Chinese hamster ovary cell line.

Pompe disease is a rare autosomal recessive disease caused by the deficiency of lysosomal acid alfa-glucosidase (GAA). GAA degrades lysosomal glycogen by catalysing the hydrolysis of the α-1, 4- and α-1, 6 glycosidic linkages. Pompe disease results in intralysosomal accumulation of glycogen in various tissues, particularly cardiac and skeletal muscles, leading to the development of cardiomyopathy, progressive muscle weakness and impairment of respiratory function.

The proposed indication is the long-term treatment of patients with a confirmed diagnosis of Pompe disease (acid alfa-glucosidase deficiency).

The Committee agreed that alglucosidase alfa should be classified as a prescription medicine.

Recommendation

• That perflutren should be a general sale medicine.
• That the following medicines should be added to the schedule as prescription medicines:
  • Daptomycin
  • raltegravir
  • Ixabepilone
  • Laropiprant
  • Alglucosidase alfa-rch

8 Harmonisation of New Zealand and Australian schedules

8.1 Update on harmonisation matters

The Secretary updated the Committee on recent recommendations for harmonisation which had been made by the MCC and adopted by the NDPSC.

8.2 Recommendation made by the NDPSC to the MCC in February and June 2007

8.2.1 Pyrethrins

At the time this recommendation was made pyrethrins were not scheduled in New Zealand and were included in Schedule 5 in Australia. Schedule 5 medicines are substances with a low potential for causing harm, the extent of which can be reduced through the use of appropriate packaging with simple warnings and safety directions on the label. In effect, pyrethrins were therefore harmonised.

The NDPSC had subsequently moved medicines containing more than 10% of pyrethrins to S2/pharmacy-only medicines and had recommended that New Zealand should harmonise on this.

As there were no current pyrethrin products on the New Zealand market and previous products contained less than 2% of pyrethrins, the Committee agreed to harmonise with the Australian classification.

Recommendation

That medicines containing more than 10% of pyrethrins should be pharmacy-only medicines

8.2.2 New medicines scheduled in Australia but not in New Zealand

The following new chemical entities had been scheduled as prescription medicines in Australia but had not yet been classified in New Zealand:

Sitaxentan

Sitaxentan is indicated for the treatment of pulmonary hypertension in patients with WHO Functional Class III symptoms to improve exercise capacity. Efficacy has been shown in primary pulmonary hypertension and in pulmonary hypertension associated with connective tissue disease and congenital heart disease.

Paricalcitol

Paricalcitol is a synthetic analog of calcitriol, the metabolically active form of vitamin D, indicated for the treatment of secondary hyperthyroidism in chronic kidney disease.

Ranibizumab

Ranibizumab is a recombinant humanised monoclonal antibody fragment related to bevacizumab that binds to and inhibits vascular endothelial growth factor, a stimulant of angiogenesis that is thought to play a role in the neovascularisation and retinal changes associated with age-related macular degeneration.

Galsulfase

Galsulfase is a recombinant human arylsulfatase B and is used as enzyme replacement for the treatment of mucupolysaccharidosis VI, a lysosomal storage disorder that results in the accumulation of the glycosaminoglycan substrate dermatan sulfate in the lysosomes with consequent widespread tissue and oxygen dysfunction.

In the interest of harmonisation, the Committee agreed that these medicines should be included in the New Zealand schedule as prescription medicines.

Recommendation

The following medicines should be classified as prescription medicines:

• Sitaxentan
• Paricalcitol
• Ranibizumab
• Galsulfase

8.2.3 Stimulant laxatives to general sale

The classification of stimulant laxatives had been considered on several previous occasions by the Committee. On each occasion the Committee had upheld its initial view that stimulant laxatives should be classified more restrictively than bulk laxatives. This was in order to promote bulk laxatives as a first line treatment and to afford an element of control over sales of products. Pharmacists had been constantly aware of attempts by anorexics to abuse stimulant laxatives.

In June 2005 the Committee considered a recommendation from the NDPSC to harmonise on the unscheduled status of stimulant laxatives. The Committee did not accept the NDPSC recommendation and, in turn, recommended that Australia should harmonise with the New Zealand pharmacy-only classification of these medicines.

The recommendation applied to the following stimulant laxatives:

• aloin
• aloes
• bisacodyl
• colocynth
• jalap resin
• sennocides
• sodium picosulfate

The NDPSC had subsequently reviewed the safety of stimulant laxatives and could see no safety issues to justify moving them to a more restrictive level of access in Australia. Abuse of products did not appear to occur to the same degree in Australia or to elicit the same degree of concern as it did in New Zealand. The NDPSC had therefore reiterated its recommendation that New Zealand should harmonise on the unscheduled status of stimulant laxatives.

The Committee considered the background papers and the discussion about stimulant laxatives which took place at the June 2007 meeting of the NDPSC. Consideration was also given to a comment from the Eating Difficulties Education Network which was strongly against any relaxation of the classification status of stimulant laxatives.

Members acknowledged that it was not only young women who abused laxatives. One member had had experience of older women abusing laxatives also, and had received a report from another pharmacist of an older woman 70 years of age who was taking up to 30 tablets per day. Although it could be difficult to know whether or not a consumer was intending to misuse or abuse a product, there were guidelines in place in pharmacies for the sale of laxatives and the opportunity to offer advice at the point of sale. It was suggested that the pharmacy profession might not be as aware of the abuse or misuse problem in Australia as the products were not scheduled and could be purchased from outlets other than pharmacies.

The Committee was unanimous in its decision to abide by its earlier decision that stimulant laxatives should be classified as pharmacy-only medicines.

Recommendation

That there should be no change to the current pharmacy-only classification of stimulant laxatives.

9. For the next meeting

• Cough and cold medicines in children under 2 years of age. (See agenda item 5.1.2)
• Chloramphenicol to restricted medicine in eye preparations. (See agenda item 5.2.9)
• Codeine in over-the-counter combination products. (See agenda item 6.2.1)
• Potassium in glucosamine sulfate complexed dietary supplements. (See agenda item 5.2.4)

10 General business

The Chairman told the Committee that he would like to investigate the use of electronic means to provide the agenda papers for meetings. While this would require that members to do all their preparatory work at a computer, it would cut down on the need to carry large amounts of paper and for the need for multiple photocopying of agenda papers. He said that the NDPSC now received all its papers on CD. While there had been some initial doubts from NDPSC members, they were now happy with this method. The Committee agreed that it would be willing to trial this.

The meeting ended at 4pm