Welcome

Apologies

Confirmation of the minutes of the 50^th meeting held on Tuesday 12 November and Wednesday 13 November 2013

Declaration of conflicts of interest

1. Dr Yousuf declared that he worked as a Medical Advisor for Pfizer Limited on sildenafil from 2001 to 2003, and as a Clinical Research Physician at Eli Lilly and Company on tadalafil in 2003. The Committee agreed that as Dr Yousuf has no financial interest in either company, and that his work as an Advisor was over a decade ago, he could participate fully in the discussion.

Matters arising

Objections to recommendations made at the 50^th meeting

Sildenafil - proposed reclassification from prescription medicine to restricted medicine
(Silvasta, Douglas Pharmaceuticals Limited)

Background

At the 41^st meeting on 14 May 2009, the Committee recommended that the analogues of sildenafil, tadalafil, and vardenafil should be classified as prescription medicines.

At the 50^th meeting on 12 and 13 November 2013, the Committee recommended that sildenafil 25 mg, 50 mg and 100 mg film coated tablets (Silvasta) should not be reclassified from prescription medicine to restricted medicine, when supplied by a pharmacist who has successfully completed the approved training programme and is accredited to supply sildenafil, for the treatment of erectile dysfunction in males aged 35-70 years.

A valid objection was received to the recommendation made by the Committee at the 50^th meeting. The objection stated that some of the intended points of the proposal were not completely understood by the Committee, and in addition the objector provided further supporting data on the safety and benefits of the proposed reclassification.

The objection stated that in the time since the recommendation had been made by the Committee at the 50^th meeting, the company had consulted with two cardiologists, and four general practitioners about the screening tools and process. The company felt that the intent of the screening tool had been misinterpreted as a method to reduce the workload of general practitioners. The company stated that on the contrary, the intent would be to increase the number of men visiting their general practitioners following referral after the screening process. The company reiterated that men presenting with erectile dysfunction and seeking the supply of sildenafil are displaying a potential warning sign of cardiovascular risk, and the proposed screening process would allow pharmacists to initiate the conversation of heart health and diabetes checks with their general practitioner.

The company revised their screening tool following advice from the Committee at the 50^th meeting. The updated screening tool would no longer attempt to estimate cardiovascular risk, and instead focus on screening out at-risk men who:

• are smokers
• have self-reported high cholesterol
• have diabetes
• have had a previous coronary intervention.

The company stated that the revised screening tool would identify a low-risk population of men for whom the supply of sildenafil by a pharmacist would be reasonable, while at the same time, providing encouragement for all men presenting with erectile dysfunction to visit their doctor for a heart health and diabetes check. The company also stated that the resupply of sildenafil would only occur once a heart health and diabetes check had been carried out.

In the objection, the company provided evidence that indicated men do not discuss sexual problems such as erectile dysfunction with their general practitioner because:

• they don't believe it is a medical issue
• they are too embarrassed to discuss it with their doctor
• of the cost of a doctor's visit.

The objection also included references that demonstrated men from Spain and Greece, where sildenafil is available from a pharmacist, often regard their pharmacists as the first health professional to contact regarding their erectile dysfunction rather than their general practitioners.

Sildenafil and its structural analogues are currently classified as prescription medicine.

Comments

A total of six pre-meeting comments were received during the consultation period. Four of the comments supported the reclassification for the following reasons:

1. men rarely make an appointment to see the doctor about erectile dysfunction as they often think the problem is too trivial, from a medical point of view
2. it is possible for pharmacists to be trained to screen for, and deal with erectile dysfunction that has a purely psychological origin
3. the proposed substantial cardiovascular risk screening to be performed by pharmacists would mean that patients could receive not only timely access to sildenafil, but also early cardiovascular disease detection
4. the improved convenience of obtaining sildenafil from a pharmacist would reduce the number of men attempting to import the medicine from overseas via the internet
5. community pharmacies are already audited by Medicines Control every three to five years, where the validity of pharmacy equipment and the adherence to standard operating procedures is assessed.

Two of the comments opposed the reclassification for the following reasons:

1. based on the draft algorithm for sildenafil supply by pharmacists, men could still be supplied with sildenafil even if they have not had a full cardiovascular risk assessment
2. erectile dysfunction is a red flag for underlying vascular disease. All patients being offered treatment for erectile dysfunction require a comprehensive cardiovascular assessment that includes laboratory tests for fasting serum lipid profile, fasting plasma glucose and glycated haemoglobin. The proposal does not stipulate the need for these laboratory tests
3. differentiating between psychogenic and organic erectile dysfunction can be a challenging procedure, requiring a detailed history, focussed examination, and a number of laboratory tests
4. the reclassification of sildenafil to restricted medicine could exacerbate the recreational misuse of this drug
5. the risks of drug interactions with sildenafil are of particular concern if the patient is seeing a pharmacist who may not be aware of their concurrent medications. This risk is amplified if the pharmacist is not the patient's usual pharmacist.

Discussion

The Committee noted that the consultation with general practitioners and cardiologists had created a significant improvement to the application. The Committee felt that the recommended changes to the screening process from the cardiologists were an improvement, and that the emphasis on encouraging men presenting with erectile dysfunction to visit their general practitioner for a heart health and diabetes check was appropriate. The Committee suggested that the application overall would have benefited from a more comprehensive critique from medical professionals.

The Committee were still unsatisfied with the post-marketing study, and questioned the value that this would add to the management of risks. One Committee member pointed out that they were not comfortable reclassifying a medicine if it would need a post-marketing study to ensure that it is safe.

The Committee were concerned with the fact that the company would essentially be taking on responsibility for accreditation of pharmacists and that the post-marketing study would be a vehicle for the company to monitor and regulate pharmacists. The committee were concerned that this undermined the role of the Pharmacy Council.

The Committee were in agreement that the proposed reclassification would be acceptable with some amendments. These would include minor changes to the screening tool such as including an obligation for the pharmacist to contact the patient's general practitioner, but with the option for the patient to opt-out if they were not comfortable with their general practitioner being contacted. The Committee also felt that the mystery shopper and post-marketing study were not essential prerequisites for the reclassification.

In addition, the Committee noted that the pack size would need to be defined for future proofing. The Committee agreed that the current packaging containing not more than 12 tablets was appropriate.

The Committee concluded that the reclassification could be progressed, providing the applicant agreed to the required amendments. The Committee noted that reclassification of sildenafil to a restricted medicine would prevent the Medsafe Investigation and Enforcement team from being able to intercept sildenafil at the border. For this reason the Committee agreed that it would be important that the reclassification was worded as a 'prescription medicine except when…'.

Recommendation

That the company should be offered the opportunity to proceed with the reclassification of sildenafil from a prescription medicine to a prescription medicine; except when supplied by a pharmacist who has successfully completed the approved training programme for the treatment of erectile dysfunction in males aged 35-70 years.

That the screening tool should require pharmacists to contact the patient's general practitioner, with the option for the patient to opt-out.

That if unhappy with the proposed amendments, the company should be offered the opportunity to withdraw their application.

Review of the classification criteria

At the 47^th meeting on 1 May 2012, a Committee member suggested that revisiting the criteria used when considering a medicine for reclassification for non-prescription sale should be added to the agenda of the next meeting.

At the 48^th meeting on 30 October 2012, and the 49^th meeting on 17 June 2013 the Committee recommended that:

1. the classification criteria would be considered at the next meeting
2. Medsafe should put together a paper with the outcome of the United Kingdom consultation and classification criteria options for discussion at the next meeting
3. Medsafe should revise the paper as discussed
4. the Medsafe paper should be agreed out-of-session by the Committee and added to the agenda of the next meeting to allow for public consultation
5. the Medsafe paper should be considered at the next meeting alongside the consultation and review of the medicines and poisons scheduling arrangements in Australia.

At the 50^th meeting on 12 and 13 November 2013, the Committee recommended that:

1. the heading "Phases of the classification process" be changed to "Should the reclassification submission be successful…"
2. the heading of Part B be changed from "Reasons for requesting classification change" to "Reasons for requesting classification change including benefit-risk analysis"
3. the description in Part B "this section should be supported where relevant by the following" be reworded to remove any confusion about what is required in the application
4. Point 7 in Part B should be changed to "Contraindications and precautions"
5. the sentence "late comments on agenda items cannot usually be accepted" be changed to "late comments on agenda items may not be accepted"
6. the principles when considering a medicine for non-prescription under Phase 3: Meeting and MCC recommendations be amended to:
   1. show substantial safety in use in the prevention or management of the condition or symptom under consideration
   2. be diagnosed and managed by a pharmacist
   3. be easily self-diagnosed and self-managed by a patient
7. the statement "Those who have made submissions to the MCC receive an email explaining the outcome before the minutes are published" be changed to "Those who have made applications to the MCC receive an email explaining the outcome before the minutes are published"
8. Medsafe consider providing applicants with more than 24 hours notice regarding the submission outcome before publication of the minutes
9. clarity be provided around the statement "Medsafe will advise the objector of the outcome and give the original applicant a chance to comment to the MCC about the objection", explaining that the objections will made available to the applicant to respond before the objection goes to the MCC.

The revised Medsafe paper was presented with the agenda of the 51^st meeting for consultation. During the consultation period, two pre-meeting comments were received.

Comments

One comment supported the change to make comments on agenda items publicly available, stating that the change would increase the transparency of the decision-making process. The other comment stated that the Committee should take further steps to ensure that sufficient information included in reclassification applications should be made publicly available so to inform the consultation process.

Discussion

The Committee discussed the issue of commercial sensitivity, reviewed in respect of a recent application. The members agreed that information that constitutes intellectual property was appropriate to be withheld from public consultation. However, the Committee were in agreement that reference lists should be made publicly available to allow the public to make informed submissions on agenda items.

The Committee believed that the description under Accuracy in Phase 3 should be amended from 'Ability of a patient to understand the medicines they are purchasing, particularly in combination'. The amendment was finalised outside the meeting in combination with Medsafe to read 'The ability of a consumer and / or healthcare professional to accurately identify a disease or condition, including the understanding of the symptoms and the possibility for alternate conditions or diagnosis. The ability of a consumer to understand how the medicine they are purchasing should be used, particularly when in addition to other healthcare products that the consumer may be using. Accuracy includes a consideration of the consequences of an incorrect understanding or diagnosis (eg, the failure to seek or receive appropriate treatment)'.

One Committee member felt that the statement under the heading Phase 9, 'When a classification change takes place a change of labelling will be required' should be amended to 'When a classification change takes place a change of labelling may be required'.

Recommendations

That the description under Accuracy in Phase 3 should be amended from 'Ability of a patient to understand the medicines they are purchasing, particularly in combination' to 'The ability of a consumer and / or healthcare professional to accurately identify a disease or condition, including the understanding of the symptoms and the possibility for alternate conditions or diagnosis. The ability of a consumer to understand how the medicine they are purchasing should be used, particularly when in addition to other healthcare products that the consumer may be using. Accuracy includes a consideration of the consequences of an incorrect understanding or diagnosis (eg, the failure to seek or receive appropriate treatment)'.

That the statement under the heading Phase 9, 'When a classification change takes place a change of labelling will be required' should be amended to 'When a classification change takes place a change of labelling may be required'.

Reclassification of articaine as a prescription medicine; except when…

An out-of-session consultation took place in January 2014 regarding the classification of articaine.

Articaine was previously classified as a prescription medicine.

The Committee recommended that articaine should be reclassified as a prescription medicine, except when used as a local anaesthetic in practice by a dental therapist registered with the Dental Council. This classification was gazetted alongside the recommendations from the 50^th meeting.

Recommendation

No further recommendation was required.

Classification of nitrous oxide as prescription 'only when supplied for inhalation'

Nitrous oxide is currently classified as a prescription medicine. At the 50^th meeting on 12 and 13 November 2013, following a suggestion from Medsafe, the Committee foreshadowed the reclassification of nitrous oxide as a prescription medicine; only when supplied for inhalation.

Recommendation

That nitrous oxide should be reclassified as a prescription medicine; only when supplied for inhalation.

Oxymetazoline - proposed reclassification from pharmacy-only medicine to general sale medicine
(Pharmaceutical Solutions in consultation with the New Zealand Retailers Association)

At the 37^th meeting on 17 May 2007, the Committee recommended that the submission from the New Zealand Association of Optometrists to allow oxymetazoline to be sold through optometry practices should be declined.

At the 38^th meeting on 14 December 2007, the Committee recommended that oxymetazoline should be exempt from pharmacy-only status when used or sold in practice by a registered optometrist.

At the 50^th meeting on 12 and 13 November 2013, the Committee recommended that:

1. oxymetazoline for nasal use, when labelled for use in adults and children over six years of age, should not be reclassified from pharmacy-only medicine to general sale medicine
2. the Committee would be willing to reconsider a revised submission with the following packaging requirements:
   1. pack size not exceeding 20 mL
   2. sealed container where the lid cannot be removed
   3. child resistant cap
3. and the following label statement requirements:
   1. do not use in children under 12 except under the advice of a doctor, nurse or pharmacist
   2. do not use in children under two
   3. do not use for longer than three days
   4. seek advice from a doctor, nurse or pharmacist if you have any medical conditions or are taking and other medications.

Pharmaceutical Solutions responded to the Committee's recommendation from the 50^th meeting.

Oxymetazoline is currently classified as pharmacy only; except for nasal use when sold at an airport; except for ophthalmic use when sold in practice by an optometrist registered with the Optometrists and Dispensing Opticians Board.

Comments

Two pre-meeting comments were received during the consultation period.

One of the comments supported the reclassification.

One of the comments opposed the reclassification for the following reasons:

1. inappropriate or prolonged use of oxymetazoline can cause rebound congestion, and the current pack size of 20 mL permits in excess of 18 day's supply
2. the risk of use in children under 12 years without professional advice
3. the risk of use in children under two years
4. there is little expected benefit to patients by having oxymetazoline available in supermarkets
5. bolder labelling would not replace professional advice available in a pharmacy.

Discussion

Pharmaceutical Solutions responded to the Committee's previous recommendation, stating that they could meet two of the suggested packaging requirements:

1. a pack size not exceeding 20 mL
2. a sealed container where the lid cannot be removed.

A potential product sponsor addressed the recommendation that general sale oxymetazoline should have a child resistant cap. The company stated that that their product would comply with the requirements of the Therapeutic Goods Order No. 80 Child-Resistant Packaging Requirements for Medicines, which specifies that a child resistant cap is not required for medicines that are in a liquid spray presentation and in a sealed container where the lid cannot be removed. The company sought clarification as to whether this was an acceptable standard for medicines supplied in New Zealand. The Committee agreed that this was an appropriate closure device to minimise the risk of harm to children through accidental ingestion of oxymetazoline solutions.

Pharmaceutical Solutions specified that they could meet two of the recommended labelling requirements:

1. do not use in children under 12 except under the advice of a doctor, nurse, or pharmacist
2. do not use in children under two.

Pharmaceutical Solutions proposed that instead of the recommended labelling statement 'do not use for longer than three days', the labelling would read 'do not use for longer than 3 days unless advised by your healthcare professional'. The Committee felt that this change decreased the impact of the warning statement, intended to prevent cases of rebound congestion, and were not satisfied with this proposal.

Pharmaceutical Solutions also proposed that instead of including the recommended labelling statement 'seek advice from a doctor, nurse or pharmacist if you have any medical conditions or are taking any other medications', the labelling would read 'seek advice from your healthcare professional if you are using any other medicines given nasally'. The Committee believed that this proposed change altered the intent of the statement and did not provide adequate warnings of the potential for contraindications against oxymetazoline.

The Committee noted that products intended to be sold in supermarkets needed to be labelled with clear and unambiguous advice to support appropriate consumer self-selection. It is inappropriate to direct the consumer to seek health professional advice when sale is intended for an environment with no such supervision.

Recommendation

That oxymetazoline for nasal use, should be reclassified from pharmacy-only medicine to general sale medicine, with the agreed packaging requirements:

1. pack size not exceeding 20 mL
2. sealed container where the lid cannot be removed
3. packaging that complies with the Therapeutic Goods Order No. 80

and the original label statement requirements proposed at the 50^th meeting:

1. do not use in children under 12 except under the advice of a doctor, nurse or pharmacist
2. do not use in children under two
3. do not use for longer than three days
4. seek advice from a doctor, nurse or pharmacist if you have any medical conditions or are taking any other medications.

Zoster (shingles) vaccine - proposed reclassification from prescription medicine to prescription medicine except when…
(Pharmacybrands Limited)

At the 50^th meeting on 12 and 13 November 2013, the Committee recommended that:

1. Zoster (shingles) vaccine should be classified as a prescription medicine except when administered to a person 50 years of age or over by a registered pharmacist who has successfully completed a vaccinator training course approved by the Ministry of Health and who is complying with the immunisation standards of the Ministry of Health
2. the reclassification is subject to the amendments being made to the checklist and information sheets, as raised by the Committee.

Pharmacybrands provided updated versions of the checklist and information sheets to the Committee.

The Committee noted an empty space on the checklist following the question 'Are you having medicines that affect the immune system?', which they believed should read 'If YES, refer to GP'.

The Committee felt that the question 'Have you had a shingles or zoster vaccination before?' was sufficient on its own, and that the subsequent statement '(in NZ in 2012 and from 2013 or in another country)' was unnecessary and should be removed.

The Committee also debated the information provided on the checklist for the pharmacist to explain the effectiveness of the vaccine to the customer. The Committee agreed that more detailed information on the absolute risk of contracting shingles was necessary.

The Committee agreed that the updated checklist and information sheets should be returned and the Chair would review all amendments on behalf of the Committee.

Recommendation

That the checklist and information sheets should be amended and returned to the Chair for review.

Ipomoea - amendment to exclude Ipomoea batatas from pharmacy-only entry

It had been brought to Medsafe's attention that Ipomoea batatas (kumara) had been unintentionally captured under the current schedule entry for Ipomoea as a pharmacy-only medicine. This would prevent the use of Ipomoea batatas in natural health products, which was not the intent of the Committee at the time of classification.

The Committee agreed that it was appropriate to leave all the stimulant laxatives captured under the Ipomoea schedule entry as they were, except for Ipomoea batatas. There is no known data to support Ipomoea batatas having a stimulant laxative effect, and as a common foodstuff, it appropriately fits the criteria of a dietary supplement. The Committee also noted that Ipomoea batatas is one of the ingredients on the Australian list of substances allowed in Listed Medicines.

The Committee agreed that a recommendation to amend the classification should be made, unless any objections were received.

Recommendation

That the schedule entry for Ipomoea should be amended to pharmacy-only medicine; except Ipomoea batatas.

Submissions for reclassification

Oral Contraceptives
(Pharmacybrand Limited and Pharma Projects Limited)

This was a company submission for the reclassification of selected oral contraceptives to allow supply without prescription by pharmacists who have successfully completed an approved training course, have become accredited, and are complying with approved guidelines.

The proposed reclassifications were:

1. desogestrel from prescription medicine to restricted medicine when not in combination and when supplied for oral contraception by a pharmacist accredited to supply oral contraception, in accordance with the approved protocol for supply
2. ethinylestradiol from prescription medicine to restricted medicine when supplied at a strength of 35 micrograms or less in combination with levonorgestrel or norethisterone for oral contraception by a pharmacist accredited to supply oral contraception, in accordance with the approved protocol for supply
3. norethisterone from prescription medicine to restricted medicine; when supplied for oral contraception by a pharmacist accredited to supply oral contraception, in accordance with the approved protocol for supply
4. levonorgestrel from:
   • restricted medicine; in medicines for use as emergency post-coital contraception when in packs containing not more than 1.5 milligrams except when sold by nurses recognised by their professional body as having competency in the field of sexual and reproductive health
     
     to
   • restricted medicine; when supplied for oral contraception by a pharmacist accredited to supply oral contraception, in accordance with the approved protocol for supply, or in medicines for as emergency post-coital contraception when in packs containing not more than 1.5 milligrams except when sold by nurses recognised by their professional body as having competency in the field of sexual and reproductive health.

Background

At the 14th meeting on 2 November 1994, the Committee considered the safety record of oral contraceptives and decided to produce an extensive public consultation plan before making any recommendation on the reclassification of oral contraceptives.

At the 15^th meeting on 20 November 1995, the Committee recommended that further consideration of the reclassification of oral contraceptives should be deferred until the results of the several ongoing studies had been published and analysed.

Comments

A total of fifteen pre-meeting comments were received during the consultation period. Six of the comments supported the reclassification for the following reasons:

1. the submission outlines the requirement of blood pressure checks, which many community pharmacies in New Zealand already offer
2. the proposal would improve access for some women living in rural and isolated communities
3. the benefit of over-the-counter access outweighs the low risk
4. the proposal would reduce the burden on general practice
5. a lot of women already commonly have repeat prescriptions generated over the phone or by speaking with the practice nurse
6. emergency contraceptive pill consultations would be an ideal opportunity for pharmacists to offer a supply of an oral contraceptive
7. pharmacist supply of oral contraceptives is happening already in Australia, Canada, the United States, and the United Kingdom
8. the proposal fits the government model of 'better, sooner, more convenient health care' by removing the barriers to access a medicine that has a similar safety profile to other non-prescription medicines.

Seven of the comments opposed the reclassification for the following reasons:

1. the proposed reclassification is unlikely to reduce costs for contraceptive users
2. internationally and in New Zealand, long-acting reversible contraception (LARC) is becoming increasingly encouraged and is much more effective in practice than oral contraceptive pills
3. fragmentation of the health care system can result in inefficiencies and safety risks
4. despite attending an 'approved training course' a pharmacist does not have the medical training and understanding to adequately look at all the other aspects any competent general practitioner would
5. a general practice consultation to discuss and prescribe contraception provides an opportunity to explore other health issues including sexually transmitted infection checks
6. contraception consultations are an excellent opportunity to offer cervical screening. This would be lost if the reclassification were to occur
7. the proposal would lead to a disconnect ahead of harmonisation activities leading towards an Australia New Zealand Therapeutic Products Agency (ANZTPA)
8. oral contraceptives are associated with rare, but serious side effects including stroke in women who suffer from migraines with aura and venous thromboembolism.
9. the requirement for a prescription does not constitute a significant barrier to accessing oral contraceptives in New Zealand
10. there may be financial incentives for pharmacists to supply oral contraceptives over other methods and to sell the brand with the highest mark-up.

Several other points regarding the proposed reclassification were raised:

1. pharmacists should be able to write repeat prescriptions following initial consultation with a general practitioner
2. there is a need for an approved programme capable of certifying pharmacists to provide the service. A procedure needs to be established to determine how certification of a pharmacist to provide oral contraceptives would be granted, monitored, and if necessary, revoked
3. oral contraceptive prescribing could be extended to yearly as an alternative to this proposal.

Discussion

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

The Committee agreed that the risk:benefit profile of oral contraceptives was similar to other restricted medicines.

The observers explained that the evidence in the United States demonstrated that improving access to oral contraceptives increased their uptake among women at risk of unwanted pregnancy, providing a clear benefit to widening access. The Committee agreed that there was no question that the opportunity for women to obtain their oral contraception from a pharmacist would be more convenient than having to visit a general practitioner; however several Committee members felt that the risk of fragmentation of care might lead to poorer continuation of treatment.

The Committee reviewed a subset of data on the number of women using the levonorgestrel emergency contraceptive pill (ECP) following its reclassification to a restricted medicine. The Committee noted in the data that the number of women obtaining the ECP through their general practitioner or family planning had remained stable, while the number obtaining the ECP through their pharmacist had grown. This indicated that the size of the market had increased, and that the reclassification was satisfying an unmet need. The Committee noted that this could potentially equate to an unmet need for the supply of oral contraceptives without a prescription.

The Committee were also in agreement that a woman entering a pharmacy to obtain the ECP would provide an unparalleled opportunity to offer the immediate provision of ongoing methods of contraception. One member of the Committee suggested that as an alternative to the current proposal, pharmacists could be trained to offer a 3-month supply of oral contraceptives during an ECP consultation.

The Committee felt that a major problem with the application was the lack of collaborative work conducted with general practitioners, and that the emphasis appeared to be entirely on offering opportunities to pharmacists rather than improving the availability of primary care. The Committee also agreed that there were gaps in the proposal which were likely a result of not consulting with general practitioners.

The Committee were in agreement that integration of healthcare rather than fragmentation was the way forward. One Committee member stated that they acknowledged pharmacists were capable of managing the medicine but they were not convinced that pharmacists could manage the patient completely.

The family planning model of collaboration between nurses and doctors was used as an example of the type of communication and integration the Committee would like to see with pharmacists. The Committee stated that this was a fantastic opportunity to encourage integration, but only if done correctly.

The Committee noted the large number of negative submissions made by general practitioners was indicative of the fact that health professionals in this area feel as if they are being excluded from an important part of primary health care, and that the approach taken by Pharmacybrands did not support the integration model. The Committee recommended that the applicants should look to resolve many of the issues raised by the submissions opposing the reclassification.

Committee members agreed that this was an unusual proposed reclassification for the chronic use of a medicine over years, rather than an immediate medicine such as vaccinations and trimethoprim. As such, the Committee believed that the only way this proposal would work is if general practitioners and other members of the health professional community supported it. The Committee considered that future applications to downschedule medicines should include references to consultation with the medical fraternity as a whole.

In conclusion, the Committee agree that the proposed reclassification could work with the appropriate degree of coproduction and collaboration, and would be a significant driver for integration. However the current application did not reach that target.

Recommendation

That desogestrel, ethinylestradiol, levonorgestrel, and norithisterone should not be reclassified from their current schedule entries.

Diclofenac transdermal patches - proposed reclassification from general sale medicine to pharmacy-only medicine
(Novartis Consumer Health Australasia Pty Ltd)

Purpose

This was a company submission for the reclassification of diclofenac in transdermal preparations for topical use containing 140 mg or less of diclofenac from general sale to pharmacy-only medicine.

Background

The Committee initially considered a reclassification of topical preparations at the 3^rd meeting on 17 September 1985. On receiving further information on the reclassification proposal at the 4^th meeting on 11 March 1986, the Committee recommended diclofenac in preparations for dermatological use be reclassified as pharmacy-only medicines.

At the 18^th meeting on 15 October 1997, the Committee recommended that diclofenac for topical use should become a general sale medicine.

At the 46^th meeting on 15 November 2011, the Committee recommended that diclofenac for the treatment of solar keratosis should be reclassified as a prescription medicine.

At the 49^th meeting on 17 June 2013, the Committee considered harmonising with the Australian Schedule 2 (pharmacy-only) entry for diclofenac, which includes transdermal preparations for topical use containing 140 mg or less of diclofenac. The Committee decided not to harmonise because in New Zealand, diclofenac in preparations for external use other than for the treatment of solar keratosis, is already classified as a general sale medicine. Harmonising would result in a more restrictive classification with a more controlled dose than other products which would be left at general sale.

The premise of the submission was that the lack of harmonisation between Australia and New Zealand results in different labelling requirements for the same product in either country. The company claimed that low sales volumes for New Zealand means that it would not be commercially viable to launch products with specific New Zealand labelling.

In New Zealand, diclofenac is currently classified as:

• prescription; in preparations for the treatment of solar keratosis; except when specified elsewhere in the Schedule; except in preparations for external use other than for the treatment of solar keratosis
• restricted; in solid dose form in medicines containing 25 mg or less and more than 12.5 mg per dose form in packs containing not more than 30 tablets or capsules
• pharmacy-only; in solid dose form in medicines containing 12.5 mg or less per dose form in packs containing not more than 30 tablets or capsules and with a recommended daily dose of not more than 75 mg
• general sale; in preparations for external use other than for the treatment of solar keratosis.

Comments

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

1. pharmacists and pharmacy staff will be able to provide appropriate advice on how to use transdermal patches
2. harmonising the New Zealand classification with Australia will allow common packs to be marketed in both countries, which makes sense in light of the future alignment of the medicine regulatory agencies.

Discussion

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

The observers confirmed with the Committee that no application to market the transdermal patch in New Zealand had been made at the time of the meeting, and a future application was dependant on the reclassification being successful. The observers explained that they had produced bioequivalence studies comparing the patch with other overseas products and that a phase III trial was currently under way.

The Committee discussed the pharmacokinetic data presented in the application, which demonstrated lower levels of absorption measured by peak blood levels in comparison to currently available topical gel preparations.

The Committee also noted that the reclassification wording would have to be altered as the proposed change would result in low-dose transdermal patches containing 140 mg or less of diclofenac becoming pharmacy only medicines, while any future high-strength products in patch form containing more than 140 mg would remain general sale medicines.

Some members of the Committee felt that a pharmacy-only classification was justifiable as it would provide an opportunity for pharmacists or pharmacy workers to explain how to apply the novel patch product and use it appropriately.

One Committee member stated that the product could be upscheduled but there was no reason to do this, beyond allowing supply of the product. The harmonisation protocol specifies that the lowest classification between the two countries should apply. The Committee were unsure as to why the more restrictive scheduling still applied in Australia.

The Committee could not reach a consensus on the proposed reclassification.

The Committee concluded that:

1. there was not sufficient evidence that there is a benefit to pharmacists providing assistance to consumers in this instance
2. evidence suggests that the product has the same safety profile as the general sale product
3. as no application had been received by Medsafe, a product may potentially never be approved or marketed
4. there is no evidence of risk to public health and refusing reclassification would be in keeping with the harmonisation protocol.

Recommendation

That diclofenac in transdermal patch preparations for topical use should not be reclassified from general sale medicine to pharmacy-only medicine.

New medicines for classification

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

Afatinib dimaleate

Giotrif is available in tablets containing 20, 30, 40, or 50 mg of afatinib dimaleate in packs containing 7, 14, or 28 tablets.

Giotrif is indicated as a monotherapy for the treatment of patients with advanced or metastatic non-squamous non-small cell carcinoma of the lung, either as first line therapy or after failure of cytotoxic chemotherapy. Tumours must have Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or L858R substitution mutations.

Afatinib dimaleate is classified as Schedule 4: prescription only medicine in Australia (10 March 2014).

Recommendation

That afatinib dimaleate should be classified as a prescription medicine.

Collagenase clostridium histolyticum

Xiaflex is available in single-use, glass vials containing 900 mcg of collagenase clostridium histolyticum as a sterile, lyophilised powder for injection.

Xiaflex is indicated for the treatment of Dupuytren's contracture in adult patients with a palpable cord.

Collagenase clostridium histolyticum is not included in the Standard for the Uniform Scheduling of Medicines and Poisons (10 March 2014) in Australia.

Recommendation

That collagenase clostridium histolyticum should be classified as a prescription medicine.

Enzalutamide

Xtandi is available as soft gelatin capsules containing 40 mg of enzalutamide.

Xtandi is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel.

Enzalutamide is not included in the Standard for the Uniform Scheduling of Medicines and Poisons (10 March 2014) in Australia.

Recommendation

That enzalutamide should be classified as a prescription medicine.

Macitentan

Opsumit is available as a 10 mg film coated tablet for once daily administration.

Opsumit as a monotherapy, or in combination with approved pulmonary hypertension treatments (phosphodiesterase-5 inhibitors or inhaled prostanoids), is indicated in patients with World Health Organisation Functional Class II, III, or IV symptoms for the treatment of:

• idiopathic pulmonary arterial hypertension
• heritable pulmonary arterial hypertension
• pulmonary arterial hypertension associated with connective tissue disease
• pulmonary arterial hypertension associated with congenital heart disease with repaired shunts.

Macitentan is not included in the Standard for the Uniform Scheduling of Medicines and Poisons (10 March 2014) in Australia.

Recommendation

That macitentan should be classified as a prescription medicine.

Simeprevir

Sovriad is available in 150 mg hard capsules for oral use.

Sovriad is indicated for the treatment of chronic hepatitis C genotype 1 or genotype 4 infection, in combination with peginterferon alfa and ribavirin, in adults with compensated liver disease (including cirrhosis) with or without human immunodeficiency virus-1 (HIV-1) co-infection who are treatment naïve or who have failed previous interferon therapy (pegylated or non-pegylated) with or without ribavirin.

Simeprevir is not included in the Standard for the Uniform Scheduling of Medicines and Poisons (10 March 2014) in Australia.

Recommendation

That simeprevir should be classified as a prescription medicine.

Harmonisation of the New Zealand and Australian schedules

New chemical entities which are not yet classified in New Zealand

Dolutegravir

Dolutegravir is indicated for the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents in adults and children over 12 years of age.

In Australia in November 2013, the delegate decided to include dolutegravir in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

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

Lurasidone

Lurasidone is an atypical antipsychotic agent indicated for the treatment of schizophrenia.

In Australia in December 2013, the delegate decided to include lurasidone in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

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

Mirabegron

Mirabegron is a beta3-adrenoceptor agonist which increases bladder capacity by relaxing the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle. It is indicated for symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in patients with overactive bladder syndrome.

In Australia in November 2013, the delegate decided to include mirabegron in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

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

Pradofloxacin

Pradofloxacin, a fifth generation fluoroquinolone, is a new veterinary 8-cyano-fluoroquinolone developed for use against bacterial infections in dogs and cats involving both aerobic and anaerobic bacteria.

In Australia in November 2013, the delegate decided to include pradofloxacin in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

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

Romidepsin

Romidepsin is an antineoplastic agent indicated for the treatment of peripheral T-cell lymphoma in patients who have received at least one prior systemic therapy.

In Australia in November 2013, the delegate decided to include romidepsin in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

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

Trametinib dimethyl sulfoxide

Trametinib dimethyl sulfoxide is a reversible allosteric inhibitor of MEK1 and MEK2 (mitogen-activated extracellular signal regulated kinases 1 and 2). The sponsor's proposed indications for use of trametinib dimethyl sulfoxide is as a monotherapy, and in combination with dabrafenib for the treatment of patients with BRAFV600 mutation positive unresectable or metastatic (Stage IV) melanoma.

In Australia in November 2013, the delegate decided to include trametinib dimethyl sulfoxide in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

That trametinib dimethyl sulfoxide should be added to the New Zealand Schedule as a prescription medicine.

Vedolizumab

Vedolizumab is immunoglobulin G1-kappa anti-[Homo sapiens alpha4beta7 integrin (lymphocyte Peyer's patch adhesion molecule 1, LPAM-1), humanised monoclonal antibody indicated for the treatment of:

• adult patients with moderate to severe ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha antagonist
• adult patients with moderate to severe Crohn's disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha antagonist.

In Australia in December 2013, the delegate decided to include vedolizumab in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

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

Vortioxetine

Vortioxetine is an antidepressant with a novel mechanism of action that belongs to a group of selective serotonin reuptake inhibitors. Vortioxetine is indicated for the treatment of major depressive disorder including prevention of relapse.

In Australia in December 2013, the delegate decided to include vortioxetine in Schedule 4 (prescription medicine) with an implementation date of 1 February 2014.

Recommendation

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

Decisions by the Secretary to the Department of Health in Australia (or the Secretary's Delegate)

Decisions by the Delegate - November 2013

1. hydroquinone and monobenzone
   
   The Advisory Committee on Medicines Scheduling (ACMS) recommended that the Schedules 2 and 4 hydroquinone and Schedule 4 monobenzone entries be amended to exclude cosmetic nail preparations containing 0.02 per cent or less from scheduling.
   
   The Committee considered harmonising with the above classification.
   
   The Committee decided that the use of hydroquinone and monobenzone in nail preparations is not for therapeutic use and therefore in this instance, these substances would not be considered medicines.
   

   Recommendation

   No further recommendation was required.
2. tylosin
   
   The ACMS recommended that the Schedule 5 entry for tylosin be deleted along with all exemptions in the Schedule 4 entry.
   
   The Committee considered harmonising with the above classification, however under New Zealand legislation, tylosin is scheduled as a veterinary medicine, and therefore no action to classify tylosin was necessary.

   Recommendation

   No further recommendation was required.
3. besifloxacine hydrochloride, loteprednol etabonate, pasireotide diaspartate and vilanterol trifenatate
   
   The ACMS recommended that Schedule 4 entries be added for besifloxacine, loteprednol, pasireotide, and vilanterol as parent compounds of besifloxacine hydrochloride, loteprednol etabonate, pasireotide diaspartate, and vilanterol trifenatate, to avoid the necessity to reconsider the scheduling entries should another salt or ester appear.
   
   The Committee considered harmonising with the above classification.
   
   Pasireotide and vilanterol are already classified as prescription medicines in New Zealand.
   

   Recommendation

   That the parent compounds besifloxacine and loteprednol should be classified as prescription medicines.

Decisions by the Delegate - December 2013

There were no unresolved recommendations.

Agenda items for the next meeting

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

1. rizatriptan
   
   At the 43^rd meeting on 13 April 2010, the Committee recommended that rizatriptan 5 mg wafers should be reclassified from prescription medicine to restricted medicine for the acute treatment of migraine with or without aura.
   
   The current classification of rizatriptan is:
   • prescription medicine; except when specified elsewhere in this schedule
   • restricted medicine; for oral use in medicines for the acute relief of migraine attacks with or without aura in patients who have a stable, well-established pattern of symptoms, when in wafers containing 5 milligrams or less per wafer and when sold in a pack containing not more than 2 wafers approved by the Minister or the Director-General for distribution as a restricted medicine.
   The Committee noted that since this reclassification, the company had not produced an approved pack.
   
   The Committee agreed to discuss potential options at the next meeting.

General business

Commercial Sensitivity of Applications

The Committee noted several submissions received commented on the lack of references in company submissions.

One Committee member felt that excluding references in an application based on claims of commercial sensitivity was unusual, and that they had not come across it before on any Committee.

The Committee agreed that documentation in an application that could be considered intellectual property could be appropriately withheld as commercially sensitive, such as training material. The Committee did not believe that a search strategy was sufficient justification to withhold a list of references from publication.

The Committee felt that all references in support of an application should be published as it is in the public interest to allow a full and proper consultation where the validity of references used can be assessed.

Recommendation

That all future applications for reclassification should include all references for publication.

Date of next meeting

To take place on a Tuesday in late October 2014. The Secretary would email members for their availability.