Revised: 23 May 2013

Committees

Minutes of the 31st meeting of the Medicines Classification Committee - 21 May 2004

Held in the Medsafe Meeting Room, 18th Floor, Grand Plimmer Tower, Wellington. Commencing at 9.30am.

Present

Dr S Jessamine (Chair)
Mrs A Shirtcliffe
Ms N Gauld
Dr J Peckham
Dr S Ryder-Lewis
Mrs C Smith (Secretary)

1. Welcome

The Chairman welcomed three new members to the Committee and members introduced themselves briefly. The Chairman then gave a presentation about the regulation of medicines. He went on to expand on the classification process, the criteria for moving medicines between the different levels of classification and the need to adhere to these criteria. He also talked about methods of decision-making within the Committee and the need to record dissent in cases where consensus was not reached. In conclusion, the Chairman explained the relationship of the Committee to the Australian National Drugs and Poisons Schedule Committee (NDPSC) and the exercise to harmonise the schedules of Australia and New Zealand.

2. Apologies

An apology was received from Dr F Hughes.

3. Confirmation of the minutes of the 30TH meeting

While it was noted that only two of the members at the current meeting had been present at the previous meeting, everyone who attended the previous meeting had been given the usual opportunity to comment on the accuracy of the minutes before they had been submitted to the Minister's Delegate.

One member felt that the Committee's view on ibuprofen had not been accurately recorded in the sentence on page 5 beginning "They concluded that while general sale classification was not associated with a significant increase in adverse reactions,..."

The member requested that the sentence be amended to read:

"They concluded that while general sale classification had not been proven to be associated with a significant increase in adverse reactions,..."

One of the members present at the previous meeting was also concerned about the record of the discussion, during the debate on ibuprofen, about the usefulness of over-the-counter (OTC) medicine labelling, in particular its ability to affect consumer purchasing activity and an apparent inconsistency in decisions made around this issue. The member felt that, on balance, the Committee had been of the opinion that there had not been enough evidence to assess accurately whether or not information on OTC medicine labels had an impact on consumer activity.

Subject to the above comments, the minutes of the 30^th meeting were confirmed as an accurate record of that meeting and were signed by the Chairman.

4. Declaration of conflict of interests

This matter was discussed in detail so that new members had a clear idea of what would constitute a conflict of interest and how any such conflict could be managed. Potential conflicts were declared and discussed and the Committee agreed that none of these matters was relevant to any of the items on the current agenda.

5. MATTERS ARISING from the 30th meeting

• Correspondence with Pharmac about access to antiemetics for use in palliative care.
  The Secretary informed the Committee that she had responded to Pharmac according to the wishes expressed by the Committee at the last meeting and that no further action was required.
• Correspondence with the Pharmaceutical Society about inclusion in the Self-Care Card on colds of a warning against the use of Buccaline as an influenza vaccine.
  The Secretary informed the Committee that the Self-Care Card on colds now contained a warning against the use of alternative products other than influenza vaccine to provide protection against influenza and that this matter was now considered to have been resolved satisfactorily.
• Independent Review of Ibuprofen 200 milligram tablets for general sale
  One of the members raised concerns about some comments made in the independent advisor's report on ibuprofen which had been commissioned by the Minister's Delegate. The member was concerned that some comments implied that members of the Committee had a vested interest in decisions made by this Committee. The member who raised the concern considered it should be recorded that all Committee members, although nominated by their professional organisations (as dictated by statute), regarded their presence on the Committee as ministerial appointments and took very seriously the requirement to act, and to be seen to be acting, independently.

5.1 Fluconazole 150 milligram single oral dose

The recommendation from the NDPSC to reclassify from prescription medicine to restricted medicine had been deferred from the 30^th meeting pending further information.

The Committee noted that since the previous meeting, the company had made a submission and was no longer seeking use of the medicine as a second-line treatment. At the previous meeting the Committee had agreed that second-line treatment would be almost impossible to implement for such a product at an OTC level of access.

Members agreed that there would be consumer convenience associated with the single dose oral product over topical products.

The compliance advantage of a single dose product was also recognised. Consumers using topical products requiring several days' application might be tempted to discontinue use of the product before completion of the recommended course because the condition had been alleviated. Such non-compliance would not be possible with a single dose.

Some concern was expressed about the lost window of opportunity for consultation on wider issues and for taking of smears if the product were to no longer require medical consultation. However, it was noted that vaginal antifungals were already available over the counter and that this product would merely add another option of treatment to those already available as OTC medicines.

The Committee considered the safety of the medicine for use in pregnancy and concluded that the risks associated with a single 150 milligram dose would be minimal. Any problems which had been reported had resulted from repeated long-term doses. The submission noted a decrease in bioavailability of ethinyl estradiol with concomitant fluconazole. Two studies from late 1990s/early 2000s indicated an increase in levels from coadministration of fluconazole. One paper suggested potential for clinically significant interaction, the other noted no threat of contraceptive failure. Members agreed that clinically significant interaction with oral contraceptives would have manifested itself over the intervening years with extensive OTC fluconazole use in the UK.

Some members were concerned that the convenience of the product would mean a move away from the use of topical preparations. Because oral doses had a longer half-life than topical dose forms, there was some concern that there would be greater potential for interactions with other medicines and complementary products. However, it was agreed that, in most cases, the potential for interactions was not likely to be significant at the intended dose and that the matter could be addressed through label warnings.

Possible resistance was also considered. As the product was subsidised only with specialist recommendation it was not widely prescribed so little was known about any local development of resistance. Research showed that while there were thought to be some problems, there was very little evidence to support the development of resistance to fluconazole when used for vaginal thrush. Information had been provided to show that the mechanism by which resistance could occur was quite different from that for bacterial resistance as there was no evidence of plasmid transfer of resistance occurring in fungi. The concerns about resistance therefore, appeared to be still at a mainly theoretical stage. It was agreed that any signs of the development of resistance would be likely to show up very quickly in other regulatory bodies. The matter could be readily addressed if this were to occur.

Members also considered the possibility of incorrect diagnosis. They agreed that there were issues surrounding use of the product in the presence of a bacterial infection. It also agreed that thrush problems often arose from other issues which could not be solved by either topical or oral antifungals. For this reason members thought it was important that consumers should recognise the symptoms of both thrush and of bacterial infections and that, ideally, they should have already had a previous diagnosis before using the product. They agreed that the symptoms for thrush should be specified on the product information as being an itchy, white, odourless discharge and that consumers should be instructed to consult a doctor if they had not previously been diagnosed with vaginal thrush or if they experienced discharge with colour or odour. Consumers should also be urged to consult a doctor if the condition had not resolved within three days or was recurrent in that it had recurred more than once in the past six months.

While they concluded that accreditation of pharmacists was not necessary for sale of the product, members agreed that they would like to see more detail in the pharmacy training programme. The company should therefore be asked to focus on its pharmacist training programme. The pharmacy education programme should include details on how to:

• identify whether there had been previous diagnosis and refer to a doctor if there had not been
• assist the consumer to recognise the classic symptoms of itchy, white, odourless discharge
• assist the consumer to recognise symptoms of other types of infection manifested by coloured discharge and/or odour and to advise seeking medical advice if these were present
• advise on questioning the consumer for signs of systemic illness such as diabetes and to refer to a doctor when such signs were present
• advise the consumer to seek medical advice if no improvement was observed after 3 days ( for consistency with CMI)
• advise the consumer to seek medical advice if the condition occurred more than twice in 6 months
• advise the consumer on the remainder of the warnings consistent with those in the CMI

Recommendation

• That single-dose 150 milligram oral fluconazole for the treatment of vaginal candidiasis should be reclassified to restricted medicine.
• That the company should be asked to focus on its pharmacist education programme with particular regard to the points made by the Committee.

5.2 Hydroquinone

Hydroquinone should be classified as a general sale medicine in hair preparations containing 1% or less and a pharmacy-only medicine for external use in medicines containing 2% or less. All other preparations should be prescription medicines.

Consideration of the above recommendation from the NDPSC had been postponed from the previous meeting as the initial recommendation had been amended and there had been insufficient time available to complete the necessary consultation time-frame for the amended proposal.

Consultation had since been undertaken with the Direct Selling Association of New Zealand to see whether the proposed change would have any impact on cosmetic products currently available. It appeared that hydroquinone was not used in cosmetics and the proposal would therefore have no impact on the cosmetic industry. The Committee agreed to recommend reclassification.

Recommendation

That hydroquinone should be classified as a general sale medicine in hair preparations containing 1% or less and a pharmacy-only medicine for external use in products containing 2% or less. All other hydroquinone products should be classified as prescription medicines.

5.3 Isosorbide dinitrate

Isosorbide dinitrate had recently been reclassified as part of the harmonisation process. Lower dose oral preparations had been classified as restricted medicines in order to be consistent with glyceryl trinitrate for acute treatment.

However, it was subsequently noted that the product currently marketed was not indicated for acute treatment. This had caused the MCC to query whether the restricted medicine classification was appropriate.

Advice was sought about whether or not isosorbide dinitrate was used for acute treatment in Australia. The wording in the Australian response referred only to treatment doses and did not specify either acute or prophylactic treatment. Although there were two products registered as S3 (restricted medicine) medicines the Committee was not able to determine whether their indications were any different from the prescription products.

Members felt that isosorbide dinitrate was inappropriately classified in New Zealand as a restricted medicine and agreed that it should be reclassified to prescription status.

Recommendation

• That all oral isosorbide dinitrate including lower dose products, should be classified as  prescription medicines
• That the NDPSC should be asked to consider a similar classification change

5.4 Phenylephrine

At the 30^th meeting the MCC had proposed that all oral dose forms of phenylephrine should be classified as pharmacy-only medicines when in preparations containing 10 milligrams or less per recommended dose. Oral preparations containing doses greater than 10 milligrams should be prescription medicines. It was proposed that there should be no oral phenylephrine preparations sold as general sale medicines.

A request had been made to defer consideration of this matter. The company concerned wished to supply an in-depth analysis but had been unable to complete this within the timeframe for the 31^stmeeting. The company had undertaken to provide objective evidence-based results to the 32^nd meeting to address the Committee's concerns about possible phenylephrine abuse.

The Committee agreed to defer consideration of the classification of phenylephrine until the 32^nd meeting. No recommendation was required at that point.

6. Submissions for reclassification

6.1 Orlistat (Xenical, Roche)

This was a company submission for reclassification from prescription medicine to restricted medicine for 120 milligram capsules for weight control including weight loss, weight maintenance and prevention of weight regain in adults with a body mass index (BMI) of 30 or more.

The Committee agreed that the safety profile of orlistat was suitable for OTC sale as a restricted medicine. Consumers could identify that they were overweight and seek treatment from pharmacists. Minimal absorption occurred and severe side-effects rarely occurred. While mild to moderate side-effects occurred relatively frequently, management of these could be addressed through consumer information and pharmacist intervention. It was agreed that if the company adopted current CMI guidelines this would cover most of the issues relating to interactions and side-effects.

Abuse of the product associated with eating disorders appeared not to engender significant concern. Anorexics seeking purchases would generally be identifiable. Pharmacists were already alert to anorexics seeking laxatives. While the product could be abused by obese bulimics, numbers of individuals with eating disorders and with a BMI of greater than 30 would be relatively few. Members agreed that the product was unlikely to cause significant harm even if were misused by those with eating disorders.

Possible vitamin deficiency was discussed in some detail with particular reference to possible deficiency in pregnancy. However, the Committee was satisfied with the finding of the Xendos study with respect to percentages of consumers whose vitamin levels fell below the mean. Members noted that the patient information recommended a diet rich in fruit and vegetables. They also noted that falls in vitamin levels appeared to occur mostly within the first 6 months and did not continue to fall. Pharmacists were trained to inquire whether or not pregnancy was a possibility at the time the sale was made and to advise accordingly. Members concluded that potential vitamin deficiency should not constitute a barrier to reclassification.

However, a number of concerns were, expressed. Some members felt that, as weight loss was only one aspect of obesity, and treatment of obesity required a change in dietary habits and an increase in exercise, there should be considerable ongoing medical support. It was noted that compliance with orlistat was generally poor and that support and motivation were considered essential.

Price was seen by some members as a barrier to access. It was thought that many of the consumers who most required treatment for obesity fell into lower income groups where obesity could be due to lower-priced and possibly poorer quality food. These consumers were considered less likely to be able to afford either the product or the standard of diet recommended for weight control. Doubts were expressed about the overall benefit to the population for this reason and it was thought that reclassification of orlistat would have little effect on the epidemic levels of obesity and diabetes found in New Zealand.

On the other hand it was noted that there were a large number of products for weight loss on the market which had not been proven to work and that there would be value in having a product available with a degree of proven safety and efficacy.

The Committee agreed that an education campaign for pharmacists was important and that good follow-up should also occur. The College of Pharmacists had expressed interest in looking at a training programme similar in nature to that for the emergency contraceptive pill (ECP). There had been a great response to the ECP programme which had shown the profession in an excellent light as willing and able to take responsibility for increased training and consumer advice. However, exemption from prescription status for accredited pharmacists, as for the ECP, was not considered by members to be required for sale of orlistat.

The fact that internet sales of orlistat without a prescription would be legal if the product were to be reclassified was of concern to some Committee members. They felt that initial face to face consultation with a properly trained health professional should be required if orlistat were to be available without a prescription. One of the Pharmaceutical Society members said that, if it were included as a standard in the Code of Ethics that a face-to-face consultation was required before an initial sale were made, then that requirement could be enforced. Disciplinary action could be taken for non-adherence to the Code of Ethics. This could be a possible tool to prevent internet and mail order sales unless a face-to-face consultation had first taken place.

Other members were not unduly concerned about internet sales. They were of the opinion that there would be no communal harm and little individual harm other than possible vitamin deficiency, resulting from use by consumers, including anorexics, with a BMI of less that 30. They saw the product as a safer and more effective product than others available on the market and could see no safety reasons for consumers not to manage their own health care.

On the basis of the concern about the need for the sale of orlistat to take place within a structured face-to-face consultation with a heath care professional, the Committee decided to defer making a recommendation about the classification of orlistat until:

• it was able to obtain assurance that face-to-face consultation would occur before an initial sale of the product
• there were assurances that a protocol for the sale of the product should be in place for the sale of orlistat by pharmacists as a restricted medicine
• there were assurances that pharmacists would be trained to sell the product according to the adopted protocol. One of the members undertook to prepare papers to present to the Pharmaceutical Society and the Pharmacy Council seeking assurance of the above points.

Recommendation

That a recommendation on the classification of orlistat be deferred until the following meeting pending assurance that a face-to-face initial consultation could be made a mandatory requirement to sale of orlistat as a restricted medicine, and that pharmacists would be appropriately trained in the sale of the product.

6.2 Simvastatin (HeartCare Plus Ltd)

This was a submission for the reclassification of 10 milligram simvastatin tablets from prescription medicine to pharmacy-only medicine.

The Committee noted a recent decision in the UK to reclassify simvastatin to pharmacy-only level. However, it was unanimous in its view that simvastatin should not be sold as a pharmacy-only medicine. Members concluded that, while the safety profile of the medicine did not present concern at the proposed dosage, there were other issues which members considered overrode the safety of the medicine per se.

Firstly, members were not convinced by the nature of the data presented in the submission to support the efficacy of a 10 milligram tablet.

In addition, elevated cholesterol level was not considered to be a self-limiting condition which was one of the criteria for OTC sale. Nor could the consumer identify the condition without professional assistance.

While elevated cholesterol level was regarded as being a widespread problem, the Committee considered its treatment was only part of the whole gamut of intervention needed to provide cardiovascular care. Members felt that pharmacy-only classification of simvastatin would put too much emphasis on only one aspect of cardiovascular health. The Committee agreed that, to determine cardiovascular risk, a detailed health assessment was required including a physical examination, access to reliable blood tests, blood pressure monitoring and assessment of family history. This could not be undertaken at pharmacy-only level.

The Committee declined the submission to reclassify simvastatin to pharmacy-only medicine on the grounds that:

• more substantial evidence on the efficacy of a 10 milligram dose would be required
• the dose might be inadequate for a number of patients and OTC use might cause them not to consult a clinician who could monitor their progress
• pharmacy-only classification would require no intervention of a health professional in the sale
• diagnosis and care of patients would require careful history-taking, and examination as well as access to laboratory services
• proper management of cardiovascular care would require intervention on a number of risk factors
• reclassification of simvastatin to pharmacy-only medicine would place undue emphasis on cholesterol level as being the major risk factor to intervention.

Recommendation

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

6.3 Triamcinolone acetonide aqueous nasal spray (Nasacort, Aventis Pharma)

This was a company submission for reclassification from restricted medicine to pharmacy-only medicine for aqueous nasal sprays containing 55 micrograms per actuation and in packs containing 120 actuations. The submission also sought a change to the OTC indication to 'allergic rhinitis' in line with recent changes to other OTC corticosteroid nasal sprays. The Committee agreed that the classification change and change to indications which had already occurred with other aqueous corticosteroid nasal spray was also appropriate for triamcinolone nasal sprays and the change to pharmacy-only medicine should be made when the product was in packaging compliant with the requirements for OTC sale in Volume 1 of the New Zealand Regulatory Guidelines for Medicines.

Recommendation

That triamcinolone should be classified as a pharmacy-only medicine when in aqueous nasal sprays delivering up to 55 micrograms per actuation when the maximum recommended daily dose was no greater that 220 micrograms and the medicine had received the consent of the Minister or the Director-General to its distribution as a pharmacy-only medicine

7. New Medicines for classification

The Committee considered the list of new chemical entities forwarded for classification from the secretary of the Medicines Assessment Advisory Committee. It was agreed that all of these fulfilled the criteria for classification as prescription medicines.

Recommendation

• That the following be classified as prescription medicines:
  • Bevacizumab
  • Bosentan
  • Eplerenone
  • Norelgestromin
  • Octocog alfa
  • Pemetrexed
  • Pregabalin
  • Sevelamer hydrochloride
  • Strontium ranelate
  • Tenofovir disoproxil fumarate

8. Harmonisation of NZ and Australian schedules

8.1 NDPSC response to MCC recommendations

There were no new responses to MCC recommendations arising from the most recent minutes of the NDPSC.

8.2 Recommendations made by the NDPSC to the MCC in October 2003

8.2.1 Trichloroacetic acid

Classify as a prescription medicine except when in preparations containing 12.5% or less for the treatment of warts other than anogenital warts.

Trichloroacetic acid had previous been removed from the schedule as a pharmacy-only medicine as part of the harmonisation process.

The Committee agreed to harmonise with the more recent NDPSC recommendation so that the only general sale medicines permitted to contain trichloroacetic acid would be preparations containing 12.5% or less for the treatment of common warts

Recommendation

That trichloroacetic acid should be classified as a prescription medicine except in preparations containing 12.5% or less for the treatment of warts other than anogenital warts.

8.2.2 Orlistat

Classify as a restricted medicine when in preparations for weight-control purposes containing 120 milligrams or less of orlistat. (See agenda item 6.1 for discussion and recommendation)

8.2.3 New prescription medicines

Add aripiprazole and fenofibrate to the schedule as prescription medicines.

These were new chemical entities for which consent to market had not yet been sought in New Zealand. The Committee agreed that these should be added to the New Zealand schedule according to the principles of harmonisation.

Recommendation

That aripiprazole and fenofibrate should be added to the schedule as a prescription medicines

9. For the next meeting

Other than those matters deferred from the current meeting there were no suggestions for additional agenda items for the next meeting.

10. General business

There were no matters of general business.

The meeting closed at 3:45pm