Revised: 23 May 2013

Committees

Minutes of the 34th meeting of the Medicines Classification Committee - 9 June 2006

Held in the Syndicate Room, Centra Auckland Airport Hotel, commencing at 1pm.

PRESENT

Dr S Jessamine (Chair)
Dr D Galler
Mrs A Shirtcliffe
Ms N Gauld
Dr J Peckham
Dr T Healy

Mrs C Smith (Secretary)

IN ATTENDANCE

Dr R Hammett (Chair, Australian National Drugs and Poisons Schedule Committee (NDPSC)

1. Welcome

Dr Jessamine welcomed two new members to the Committee. Each of the members gave a brief description of his or her background.

For the benefit of the new members, Dr Jessamine also described the way that Committee recommendations were usually made. Where consensus was not reached, a majority vote would apply and it might occasionally be necessary for him to use a casting vote. Resulting recommendations were then sent to the Minister's Delegate to be accepted or declined. Under Section 9 of the Medicines Act 1981 the Medicines Classification Committee made recommendations to the Minister of Health. However, in view of the technical nature of the recommendations of the Committee, the Minister had delegated responsibility for this area to the Director-General of Health who had, in turn, on-delegated responsibility to Don Matheson, Deputy Director-General, Public Health Directorate. While it was usual for the Minister's Delegate to accept the recommendations made by the Committee, the chairman explained that, in rare cases, Medsafe held a position different from that of the Committee and would submit conflicting advice to the Minister's Delegate. The Minister's Delegate would consider both sets of advice before accepting one of the recommendations. In such cases, Committee members would be informed in advance that conflicting advice was to be submitted by Medsafe.

2. Apologies

There were no apologies.

3. Confirmation of the minutes of the 33RD meeting AND THE RECORD OF THE OUT-OF-SESSION CONSULTATION HELD IN DECEMBER 2005

One of the members requested that the wording of agenda item 8.1.1 of the 33rd meeting on alclometasone and clobetasone be amended to reflect the market status of these two medicines in Australia. The second paragraph should be amended to read:

Although these medicines had been classified as restricted medicines in Australia for some years, there had been no products marketed. However, reclassification to over-the-counter status in the UK did not appear to have produced any problems. It was noted that these medicines were not widely used and evidence of misuse had not become apparent in the UK. Nor did.....(stet).

On the basis of the above amendment, the Committee accepted that the minutes were an accurate record of the 33rd meeting and were signed by the chairman.
In the record of the out-of-session consultation held in December 2005 one of the members pointed out a typographical error had occurred in the third paragraph of item 2, where one of the references to quassia had mistakenly been recorded as icodextrin.

On the basis of amending that reference to quassia, the Committee accepted that this was an accurate record of the results of the out-of-session consultation held in December 2005 and the record was signed by the chairman.

4. Declaration of conflict of interest

For the benefit of new members, the Chairman outlined the way in which conflict of interest was handled.

Several potential conflicts of interest were declared by one of the members. These were discussed by the Committee in the absence of that member and it was agreed that the conflicts were of a minor nature and unlikely to influence the input of the member concerned. It was agreed that the member should participate fully in all items on the agenda.

5. MATTERS ARISING from the 33RD meeting

5.1 Amphotericin: objection to recommendation to reclassify

The Pharmaceutical Society had objected to the recommendation to reclassify amphotericin from restricted medicine to prescription medicine when in lozenges for the treatment of oral candidiasis. The objection was made on the grounds that due process had not been observed in the consultation process. Consultation had since been undertaken but no further responses had been received. In addition, the sole company concerned had reiterated its support of the reclassification to harmonise with the Australian S4 (prescription) scheduling. The matter had been considered as part of the out-of-session consultation in December 2005 but had not been resolved at that time.

The Committee observed that the Pharmaceutical Society objection did not address safety issues. There were no additional safety data in the objection which would cause members to review their earlier recommendation. Nor did it contain evidence challenging the concern that OTC use of amphotericin might lead to the development of resistance to its therapeutic effects. Miconazole and nystatin were available as over-the-counter (OTC) alternatives. Unlike amphotericin, these antifungal agents were not used intravenously. Therefore issues relating to resistance were considered to be different for amphotericin than for the two former medicines.

The Chairman stated that there was no safety justification in the Pharmaceutical Society objection to cause the Committee to review its earlier recommendation to reclassify amphotericin to a prescription medicine when for the treatment of oral candidiasis. The Committee had no objection to this interpretation of the data.

Recommendation

That amphotericin for the treatment of oral candidiasis should be classified as a prescription medicine.

5.2 Zanamivir (Relenza)

The sponsor company had expressed its intention not to proceed with a submission for the reclassification of zanamivir.

5.3 Oseltamivir (Tamiflu 75mg capsules, Roche)

The Committee considered further company material in support of an earlier submission for reclassification of oseltamivir from prescription medicine to restricted medicine for the treatment and prophylaxis of influenza in adults and adolescents. At the previous meeting the Committee had requested information from the company about monitoring of resistance and about promotion of the product. The Committee had indicated that it wanted to explore possible mechanisms to allow the medicine to be available over the counter only when infection rates had crossed a prearranged threshold.

Advice had been sought from two virologists, both of whom supported OTC sale of oseltamivir once influenza had manifested itself in a particular community. Both referred to studies which suggested that a very low frequency of resistance was developing in community isolates of seasonal influenza strains despite substantial oseltamivir use. The Committee agreed that should resistance be observed to increase, a change in classification status could easily be reversed. Any classification change made at this point in time could also be reviewed by the Committee after two years if that was considered necessary.

The Chairman pointed out that there remained two main issues to be addressed by the Committee. These were firstly, whether or not there would be any harm from misdiagnosis and, secondly, the need to know how much influenza was occurring in the community.

With regard to accurate diagnosis, the Committee concluded that there were few concerns about the safety of the product and that little harm should result from inappropriate use. Members agreed that masking of more serious conditions could be delayed but the delay would probably be not much greater than for any other OTC cold or influenza product.

Concern was expressed about whether or not oseltamivir would still be effective in case of a pandemic if it were widely used for seasonal influenza. Some members felt that, as most people recover from seasonal influenza, oseltamivir should remain on prescription only so that it was not overused and might therefore be more effective in the case of pandemic influenza.

The Committee noted the following points:

• The company had reiterated its earlier statement that it would monitor resistance as part of its Tamiflu package.
• The Institute of Environmental Science and Research (ESR) had expressed a strong desire for the establishment of a national resistance monitoring system. The MCC voiced its support for this.
• ESR also indicated its willingness to inform GPs about what was happening during the winter influenza season in New Zealand. This could be extended to include pharmacists.
• Vaccination should be regarded as first-line approach to prevent influenza. The company had agreed that it would not promote the product as an alternative to influenza vaccination. However, members acknowledged that public perception often differed and this might have to be addressed.
• Availability over the counter during the influenza season would provide considerable consumer convenience.
• Availability over the counter would have no impact on national stockpiles for pandemic use. There would be increased benefit in that there would be greater stocks in the country in the case of a pandemic.
• There was provision for over-the-counter supplies to be shut down in the case of a pandemic.

The NDPSC Chairman said that, to date, the NDPSC had opted not to make oseltamivir available over the counter. The reasons for this were not so much concerns about resistance as concerns about delay in diagnosis of more serious conditions and the desire to discourage stockpiling of the product.
There was concern that if the product were to become available over the counter it could be sold legally over the internet by pharmacists. The Pharmacy Council protocol requiring an initial face-to-face consultation before the sale of restricted medicines applied only to medicines for the treatment of chronic conditions. Members were anxious to ensure that uncontrolled internet sales of this medicine did not occur.

The Committee concluded that, on the information considered to date and the external advice provided, oseltamivir should be available over-the-counter. However, this availability should be for the treatment of influenza only and not for prophylaxis. In addition, it was agreed that oseltamivir should be available over the counter only between the months of May and September when seasonal influenza epidemics were likely to occur. ESR should be asked to disseminate information about seasonal influenza to doctors and pharmacists. The NDPSC should be asked to consider harmonising on this classification. Rather than attempting to devise wording for the schedule to implement the classification change, the Committee agreed that Medsafe should be asked to devise the best way in which to put the MCC recommendation into effect.

Secretary’s Note

Prior to accepting the recommendation below referring to oseltamivir, the Minister’s Delegate sought reassurance that the Committee had given adequate consideration to resistance and monitoring issues. The Chairman prepared a report drawn from information provided to members in the agenda material. The Oseltamivir Report was ratified by all Committee members as being an accurate summary of the resistance and monitoring issues as provided in the agenda material and discussed by the MCC at the 34th meeting.

Recommendation

• That pharmacists should be able to sell oseltamivir between the months of May and September for the treatment of influenza but not for prophylaxis
• That uncontrolled internet sales of oseltamivir should not be permitted
• That Medsafe be asked to put in place the measures necessary to implement this recommendation
• That the NDPSC should be asked to harmonise on the seasonal availability of oseltamivir
• That ESR be asked to ensure that pharmacists as well as general practitioners would be advised about the occurrence of seasonal influenza.

5.4 Simvastatin (10 milligram tablets, GlaxoSmithKline)

The Committee was to have continued its consideration of the company submission for the reclassification of 10 milligram tablets from prescription medicine to restricted medicine in the light of the company response to the its concerns at the 33rd meeting about issues relating to training and protocols for OTC sale.

However, GlaxoSmithKline reported that the company was still collecting material to address matters raised by the MCC and had requested that consideration of the reclassification of simvastatin 10 milligram tablets be deferred to a later date.

6. Submissions for reclassification

6.1 Domperidone (Motilium, 10mg tablets, Janssen-Cilag)

This was a new company submission for reclassification from prescription medicine to restricted medicine. In response to the Committee's concerns about the previous submission, the company had amended the indications, pack size and labelling to address those concerns.

The latest submission was for the reclassification of 10 milligram tablets in packs containing 20 tablets for the symptomatic treatment of nausea and for the treatment of the symptoms of dysmotility-like dyspepsia, sense of fullness, feeling of abdominal distension, eructation, flatulence and heartburn.

The Committee noted that the indication for vomiting had been removed from the indications in accordance with its wishes recorded at the 33rd meeting. However, members were still not happy with the proposed indications and felt that these needed to be stated more specifically. If the product was not to be used for vomiting, this should be specified on the pack. Nor were members happy with the statement on the primary display panel of the proposed New Zealand label that the product "relieves stomach problems". They stressed that they would not be happy to see the product used for diarrhoea or for non-specific stomach problems. It was agreed that better information was needed on both the label and the package insert.

Some members did not see a place for this medicine for self-medication, regarding it as a third-line treatment for specific motility problems. They did not think that the product would be particularly effective for short-term use and agreed that there were other products such as H2 antagonists available which would provide better, more immediate relief for discomfort related to dyspepsia.
The possibility of QT prolongation was discussed. This appeared to be mainly evident with high-dose intravenous use and would be unlikely to occur with low-dose oral products unless the consumer had existing QT prolongation. It was agreed that, had QT prolongation been associated with low-dose oral products, it would probably have become evident in the UK. However, it was noted that OTC use might not allow for picking up cases of QT prolongation.

The Committee also agreed that idiosyncratic extrapyramidal side-effects were possible, particularly in young adults.

Also of concern was the potential for domperidone to affect the absorption of other medicines.

Overall, the Committee felt that the submission had not made a convincing case for the need for domperidone to be available over the counter. The submission to be reclassified as a restricted medicine was declined on the basis that:

• the indications were inappropriate for sale as restricted medicine
• the pack size was still too large for intermittent treatment
• the labelling did not adequately describe the product and did not have sufficient warning statements.

Recommendation

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

6.2 Hydrocortisone 0.5% with cinchocaine (Proctosedyl, Sanofi Aventis)

This was a company submission for the reclassification of proctosedyl suppositories and ointment from restricted medicine to pharmacy-only medicine.

The Committee noted that both components of the product were available at a lower level of classification when sold individually and were only required to be restricted medicines when in combination. Members were unsure as to what extra consumer value would be derived from requiring a pharmacist to be involved in the sale of this product. Although members thought a protocol for the sale of the product would be desirable, they recognised that this could not be required for pharmacy-only medicines.

One member had investigated possible abuse of the product and had discovered that there was anecdotal evidence of its use to treat bags under the eyes. The member reported that investigation showed that there did not appear to be overuse of the product. However, the member was aware that this pattern could change with a change of classification.

Another member said that doctors had difficulty getting consumers to admit to rectal bleeding and suggested that this might be even more difficult for pharmacists. The Committee agreed therefore that, should the reclassification proceed, the package should bear a warning for consumers to consult a doctor if they experienced rectal bleeding.

The Committee also agreed that recurrent use was not appropriate and that OTC packs should also carry a warning against recurrent use and the need for medical advice if the condition was not resolved. In addition, it was agreed that the product should be for adults only and should not be used for children. This information should also appear on the OTC pack.

Although the Committee realised that a requirement for a protocol for the sale of pharmacy-only medicines was not possible, members agreed that the Pharmaceutical Society should be asked to consult with the sponsor company about a training protocol for the sale of the product by pharmacy assistants.

If the product were appropriately labelled, members felt that masking or delaying the diagnosis of serious conditions was low. On that basis, the Committee agreed that the product would be suitable for reclassification from restricted medicine to pharmacy-only medicine.

Recommendation

• That the restricted medicine entry for hydrocortisone in rectal medicines should be amended to allow these to be sold as pharmacy-only medicines when in medicines containing 0.5% or less of hydrocortisone and when in combination with a local anaesthetic and in a quantity of not more than 30 millilitres per container or 12 suppositories per pack and in packs containing a warning:
  • against use in children
  • against recurrent use and need for medical advice if the condition persists
  • to seek medical advice in the event of rectal bleeding.
• That the Pharmaceutical Society be requested to consult with the sponsor company on a training protocol for sale of the product by pharmacy assistants.
• That the NDPSC should be asked to harmonise on the above recommendation.

7. New Medicines for classification

7.1 New chemical entities referred by the MAAC

The new chemical entities referred by the Medicines Assessment Advisory Committee for classification were considered out-of-session in December 2005 and were classified as prescription medicines.

7.2 Adrafinil

Adrafinil was a potential drug of abuse which was currently unclassified and was referred to the MCC by the Medsafe Medicines Control Team for classification.
This matter was resolved out-of-session in December 2005. Adrafinil had been classified as a prescription medicine.

8. Harmonisation of NZ and Australian schedules

8.1 Harmonisation matters arising or outstanding 8.1.1 Antihistamine use in children under two years of age

The Committee had earlier expressed concern that sedating antihistamines were available over the counter for children under two years of age. Some sedating antihistamines had been implicated in sudden death in this age group. There was also anecdotal and published evidence of misuse and abuse of these medicines in children. The Committee was unanimously of the view that sedating antihistamines should be used in this age group only under medical supervision. Members agreed that the NDPSC should be asked to harmonise on this recommendation.

Recommendation

• 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.
• That the NDPSC should be asked to harmonise on the above recommendation.

8.1.2 Icodextrin

This was a recommendation to reclassify from pharmacy-only medicine to general sale medicine on the grounds that:

• the intention was that medicines for dialysis should be general sales medicines in New Zealand
• icodextrin was an unscheduled medicine in Australia

This matter was resolved out-of-session in December 2005. Icodextrin had been removed from the schedule.

8.1.3 Kava

At the previous meeting the Committee had agreed that kava should be considered with a view to harmonising with Australia. The NDPSC had recently reclassified kava as a prescription medicine except when it conformed to the conditions below and was exempt from scheduling.

1. in preparations for oral use containing dried whole or peeled rhizome or containing aqueous dispersions or aqueous extracts of whole or peeled rhizome when labelled with a recommended daily dose of 250 milligrams or less of kavalactones:
   1. containing more than 25 milligrams of kavalactones per dose, labelled with the statement:
      WARNING: Not for prolonged use. Not recommended for use by pregnant or lactating women. May harm the liver;
   2. in tablet or capsule form containing 125 milligrams or less of kavalactones per tablet or capsule or:
   3. in the form of a teabag when the amount of dried whole or peeled rhizome does not exceed 3 grams
2. in topical preparations for use on the rectum, vagina or throat containing dried whole or peeled rhizome or containing aqueous dispersions or aqueous extracts of whole or peeled rhizome; or
3. in dermal preparations.

The Committee noted that there had been minor alterations to the above Australian schedule entries for kava since the initial recommendation to the MCC.

The Chairman said that, while a number of case reports of liver damage had been confounded by the patients' use of other OTC and prescription medicines, there had been sufficient data world-wide to constitute a signal about the safety of kava. This had led to a ban on its use in a number of countries. In some cases regulatory agencies had revoked the ban on applying for consent to market products containing kava though, to the best of his knowledge, no kava products had been through such an evaluation process to date. He said that the data indicated that the safety threshold appeared to occur around 250 milligrams per recommended daily dose though the upper limit had been set at 120 milligrams per recommended daily dose in the German Herbal Pharmacopoeia. Data indicated that while aqueous extracts appeared to be safe within these limits, high concentration ethanol and acetone extracts had been implicated in cases of liver injury. It was not clear if the safety concerns applied to all ethanolic extracts of kava lactones.

It was noted that any classification of kava would affect therapeutic or dietary supplement use but was not intended to apply to recreational use. One member commented that kava drinkers appeared to be well aware that recreational use could result in hepatitis.

Members agreed that making kava a prescription medicine except when in preparations which conformed to the NDPSC recommendation would take its use out of the hands of those such as medical herbalists and allied health professionals with expertise in its use. The doctors agreed that general practitioners did not usually have expertise in this area. They also expressed concern that the evidence presented in the submissions raised the question about whether some form of alcohol extracted products might be safe enough for general use.

The Chairman said that there were a number of options open to the Committee. These included leaving kava unscheduled, harmonising with Australia or trying to work out a suitable classification for the New Zealand situation. A further option could be to request that the NDPSC referred the matter back to the Australian Complementary Medicines Evaluation Committee for further review.

When questioned about the newly-established Interim Advisory Committee on Complementary Medicines, the Chairman pointed out that the terms of reference for that committee allowed it to look only at substances used in New Zealand which were not on the permitted ingredients list in Australia. He said, however, that the MCC could defer making a recommendation on the classification of kava at this point in time and refer the matter to the new complementary medicines advisory committee which would come into effect with the commencement of the Australia New Zealand Therapeutic Products Authority.

Although members acknowledged that the classification of kava would not be harmonised when the new agency came into effect, they agreed that the latter proposal was their preferred option.

Recommendation

• That there be no change to the current general sale status of kava
• That the matter should be referred to the new complementary medicines advisory committee for review when it came into effect under the Australia New Zealand Therapeutic Products Authority.

8.1.4 Paracetamol 665 milligram tablets

In December 2001 the Committee had considered a company submission for the reclassification of paracetamol in tablets or capsules containing more than 500 milligrams to enable 665 milligram tablets to be sold as pharmacy-only medicines rather than prescription medicines. At the time the Committee had recommended against any change to the 500 milligram level of paracetamol tablets or capsules for OTC sale.

Tablets containing 665 milligrams of paracetamol were classified as pharmacy-only (S2) medicines in Australia and the NDPSC had requested that the MCC review its earlier recommendation with a view to harmonisation.

Members acknowledged that the 665 milligram tablets had been available for some four years in Australia without evidence of an untoward number of problems related to over-use or overdose. The Committee had earlier been concerned that possible confusion of 665 milligram slow release products with lower dose 500 milligram products could result in overdosing. However this did not appear to have been a problem in Australia.

An ongoing concern was that emergency rooms might not be aware of slow release paracetamol products and therefore of the need to retest overdose patients with equivocal levels of blood paracetamol. The current paracetamol overdose treatment chart did not cater for slow release forms. Members agreed that they would like assurance from the company that a protocol for appropriate treatment would be provided for emergency rooms so that staff would be aware of the possibility that a slow release product might be implicated.

There was some discussion about the benefits or otherwise to consumers of dosing three times daily rather than the usual four doses for 500 milligram tablets. Most members also agreed that there was benefit to consumers in having a slow release product available to provide pain relief throughout the night.

The Committee agreed that there appeared to be no reason why New Zealand should not now harmonise with the Australian classification for this product. However, it did require an assurance from the company that the protocol for the treatment of paracetamol overdose should be revised to cater for possible use of 665 milligram slow release paracetamol and that this should be promoted in emergency rooms.

Recommendation

• That medicines containing 665 milligrams or less of paracetamol and more than 500 milligrams should be reclassified as pharmacy-only medicines when in slow release form
• That the sponsor company for the 665 milligram slow release product should be asked to prepare and promote a protocol for the treatment of paracetamol overdose in emergency rooms which would take into account the treatment required for slow release forms.
• That the NDPSC should be asked to harmonise on the requirement for S2/pharmacy-only medicines over 500 mg and up to 665 mg per tablet or capsule to be in slow release form only.

8.1.5 Quinine

The recommendation was that the restricted medicine entry for quinine for the prevention of cramp should be removed from the schedule and that quinine should be reclassified as a prescription medicine except in medicines containing 50 milligrams or less per recommended daily dose. No change was recommended to the current general sale classification of quinine.

This matter was resolved out-of-session in December 2005. Quinine had been reclassified as a prescription medicine except in medicines containing 50 milligrams or less per recommended daily dose.

8.1.6 Tranexamic acid

The recommendation was that tranexamic acid should be reclassified from prescription medicine to restricted medicine when for the treatment of menorrhagia in order to harmonise with the Australian classification.

There had been no response during the consultation period from the New Zealand sponsor company.

The Committee agreed that diagnostic testing was necessary to determine the cause of menorrhagia. This normally required access to ultrasound tests which was not possible for an OTC medicine. Without prior diagnosis there was potential to mask more serious conditions. Only if the problems relating to diagnosis could be addressed satisfactorily or if the underlying cause of menorrhagia had previously been diagnosed would they be happy for the product to be available as a restricted medicine.

Although tranexamic acid was an effective treatment for menorrhagia, it was recognised that there would be only a small group of consumers who would be able to use it safely because of the number of contraindications to its use. It was felt that while improved package labeling could probably identify those patients for whom it was safe to use the product, the ability to diagnose accurately the underlying cause of menorrhagia within the pharmacy remained a major issue. Furthermore, the sponsor company had not provided any information at this point and no product had been marketed over the counter in Australia for this indication.

In view of the difficulty in ensuring safe use as an OTC medicine, the Committee recommended that tranexamic acid should remain a prescription medicine and that, as no product had been marketed in Australia, the NDPSC should be asked to reconsider the S3 scheduling of tranexamic acid.

Recommendation

• That there be no change to the current prescription medicine classification of tranexamic acid.
• That the NDPSC should be recommended to reconsider the S3 scheduling of tranexamic acid to harmonise with the New Zealand classification.

8.1.7 Mepyramine

The MCC had recommended at the 33rd meeting that mepyramine for dermal use should remain a pharmacy-only medicine as there had been no reported problems in New Zealand relating to sensitisation. This recommendation had crossed with a recommendation from the NDPSC for mepyramine for dermal use move to prescription medicine because of concerns with topical use of sensitising antihistamines.

The NDPSC had subsequently harmonised with New Zealand for dermal use of mepyramine as a pharmacy-only/S2 medicine. However, the NDPSC had also recommended that, in order to complete the harmonisation process for mepyramine, New Zealand should adopt a restricted medicine entry rather than a prescription medicine entry for oral use. New Zealand had no registered oral mepyramine products. The Committee agreed to recommend the change to restricted medicine.

Recommendation

That the schedule entry for mepyramine except for dermal use should be changed from prescription medicine to restricted medicine.

8.1.8 Quassia

The recommendation was that quassia should be removed from the schedule. Quassia was formerly a pharmacy-only medicine in New Zealand. There were no products registered which contained quassia.

This matter was resolved out-of-session in December 2005. Quassia had been removed from the schedule.

8.2 Recommendations made by the NDPSC to the MCC in July 2005 8.2.1 Darifenacin

The recommendation was that darifenacin should be added to the schedule as a prescription medicine.

This matter was resolved out-of-session in December 2005. Darifenacin had been classified as a prescription medicine.

8.2.2 Cetuximab

The recommendation was that cetuximab should be added to the schedule as a prescription medicine.

This matter was resolved out-of-session in December 2005. Cetuximab had been classified as a prescription medicine.

The Committee moved on immediately to consideration of the agenda for the 35^th meeting of the MCC.