1

Welcome

The Chair opened the 53^rd meeting at 9:30 am and welcomed members and guests.

2

Apologies

There were no apologies.

3

Confirmation of the minutes of the 52^nd meeting held on Tuesday 21 October 2014

The minutes of the 52^nd meeting were accepted as a true and accurate record. The minutes were signed and dated by the Chair.

4

Declaration of conflicts of interest

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

5

Matters arising

5.1

Objections to recommendations made at the 52^nd meeting

No valid objections had been received.

5.2

Azelastine for nasal use

Medsafe received a New Medicine Application for a nasal spray that contains 0.15% ^w/_v azelastine hydrochloride and is proposed to be indicated for the treatment of hayfever symptoms caused by seasonal and non-seasonal allergies including pollen, house mites and pet hair.

Azelastine is currently classified as:

• prescription medicine; except when specified elsewhere in this Schedule
• pharmacy-only medicine; for nasal use; in topical eye preparations containing 0.05% or less.

The current nasal use classification does not include a strength limit. The only azelastine-containing nasal spray (Azep) currently approved in New Zealand contains (0.1% ^w/_v) of azelastine hydrochloride.

At the 16^th meeting on 24 April 1996, the Committee recommended that azelastine be classified as a prescription medicine.

At the 17^th meeting on 15 May 1997, as a result of a company submission, the Committee recommended that azelastine be reclassified from prescription medicine to pharmacy-only medicine for nasal use. The minutes did not record any discussion regarding strength. However, the only product under consideration at the time was Azep (formerly called Rhinolast), a nasal spray containing 0.1% ^w/_v of azelastine hydrochloride.

Medsafe's submission recommended that a 0.15% ^w/_v azelastine hydrochloride nasal spray should be classified as a pharmacy-only medicine. Medsafe also recommended that, to avoid any confusion in the future, a strength limit should be included in the pharmacy-only classification of azelastine for nasal use. A reasonable limit would be 0.15% ^w/_v azelastine hydrochloride as no products (approved or pending) contain more than this concentration and acceptance of this concentration limit would harmonise with the scheduling of azelastine in Australia. The classification wording for azelastine should, therefore, be amended to:

• prescription medicine; except when specified elsewhere in the Schedule
• pharmacy-only medicine; for nasal use in preparations containing 0.15% azelastine hydrochloride or less; in topical eye preparations containing 0.05% or less.

Two pre-meeting comments were received during the consultation period. Both supported Medsafe's submission to clarify the classification of azelastine as a pharmacy-only medicine. A strength limit in a medicine classification removes any potential confusion and there was no awareness of any evidence documenting any specific risk of adverse effects with the slightly higher strength of the nasal spray.

The Committee agreed that the evidence showed no increased risk of adverse events at the 0.15% strength.

Recommendation

That 0.15% ^w/_v azelastine hydrochloride nasal spray should be classified as a pharmacy-only medicine. The pharmacy-only classification of azelastine for nasal use should be amended to: for nasal use in preparations containing 0.15% azelastine hydrochloride or less; in topical eye preparations containing 0.05% or less.

5.3

Ketoprofen for topical use

Medsafe submitted an application to reclassify topical ketoprofen in response to it receiving an application to market a new topical product. The key driver for the Medsafe submission was a decision made by the European Medicines Agency (EMA) to reschedule topical ketoprofen due to concerns about phototoxicity.

At the 29^th meeting on 22 May 2003, the Committee recommended that ketoprofen for topical use should be reclassified from pharmacy-only medicine to general sale medicine.

At the 37^th meeting on 17 May 2007, the Committee recommended that the prescription medicine entry for ketoprofen should be amended to read 'except for dermal use; except when specified elsewhere in this Schedule'. The amendment had no regulatory impact on any products on the New Zealand market.

Ketoprofen is currently classified as:

• prescription medicine; except when specified elsewhere in this Schedule; except for dermal use
• restricted medicine; in solid dose form containing 25 mg or less per dose form in packs of not more than 30 capsules or tablets
• general sale medicine; for dermal use.

In 2010, the EMA reviewed the safety of ketoprofen for topical use and concluded that there is a risk of:

1. photosensitivity reactions, including photoallergy reactions (even in the case of hazy sun)
2. co-sensitisation with octocrilene (an ingredient that may be present in some cosmetic and hygiene products).

In the opinion of the EMA, while the benefits of topical ketoprofen continue to outweigh its risk, further measures should be put in place to minimise the risk of adverse skin reactions.

As a consequence, the EMA recommended a number of risk minimisation measures. These included additional warnings regarding photoallergy and skin reactions after co-application of octocrilene-containing products, and a recommendation that ketoprofen topical products be subject to medical prescription. The EMA report, and annexes, are available under the 'All documents' tab at www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Ketoprofen_topical/human_referral_000238.jsp&mid=WC0b01ac%2005805c516f.

The classification of ketoprofen was not reconsidered in New Zealand at the time the EMA made its decision as no topical ketoprofen products were on the market.

However, a New Medicine Application for a topical 2.5% ketoprofen gel has now been received. Following a request from Medsafe, the Committee considered whether it was appropriate for ketoprofen for topical use to remain unclassified (as a general sale medicine) or whether, in view of the EMA recommendations, it should be reclassified.

Three pre-meeting comments were received during the consultation period. All three supported reclassifying ketoprofen for topical use. One pre-meeting comment recommended a restricted medicine classification because exposure to ultraviolet light during the summer months is high in New Zealand. A restricted medicine classification was justified by concerns that the complexity of photosensitivity reactions required explanation from a pharmacist. One pre-meeting comment recommended a pharmacy-only medicine classification because a similar product is classified as a pharmacy-only medicine in Singapore and also other topical products known to cause photosensitivity or other serious skin related adverse reactions on rare occasions are classified as pharmacy-only medicines in New Zealand.

The Committee expressed concerns regarding the management of safety issues with respect to risks of photosensitivity and photo allergy. The Committee considered ketoprofen gel to be second or third line therapy that should only be used when other topical products failed to produce the clinical response desired by the consumer. The Committee noted that as ketoprofen had not been available for some time in New Zealand there should be few, if any, patients routinely using topical ketoprofen.

Due to the increased risks associated with the use of topical ketoprofen and the availability of other topical non-steroidal agents that are safer to use, the Committee considered that the EMA's recommendations for risk minimisation were appropriate.

Recommendation

That ketoprofen for dermal use should be reclassified from general sale medicine to prescription medicine.

5.4

Omeprazole - proposed reclassification from pharmacy-only medicine to restricted medicine

At the 52^nd meeting on 21 October 2014, the Committee recommended that:

• omeprazole, in solid dose form containing 10 mg or less, should not be reclassified from pharmacy-only medicine to general sale medicine for the short-term symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and older
• that Medsafe's Pharmacovigilance Team should be asked to produce a report for the next meeting on whether there was any new evidence of interactions of omeprazole with other medicines to support a reclassification to restricted medicine.

The Committee considered a report from Medsafe’s Pharmacovigilance Team. Medsafe's report concluded that there was no evidence that interactions resulting in increased levels of omeprazole are harmful. Interactions decreasing the bioavailability of omeprazole can be managed by increasing the omeprazole dose.

Medsafe's conclusions were derived from a review of the scientific literature and consideration of data from the Centre for Adverse Reactions Monitoring (CARM).

The Committee also reviewed factors considered prior to their previous decision regarding reclassification of omeprazole made at the 52 ^nd meeting on 21 October 2014 in light of the additional data presented at this meeting.

In light of there being no new evidence identified to support any change to the current risk profile of omeprazole, the Committee recommended that omeprazole, in solid dose form containing 10 mg or less, for the short-term symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and older should not be reclassified.

Recommendation

That omeprazole, in solid dose form containing 10 mg or less, for the short-term symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and older should not be reclassified from pharmacy-only medicine to restricted medicine.

5.5

Paracetamol in combination with phenylephrine
(Maxiclear Sinus and Pain Relief and Maxiclear Cold and Flu Relief, AFT Pharmaceuticals)

At the 52^nd meeting on 21 October 2014, the Committee recommended that paracetamol in combination with phenylephrine should not be changed.

The Committee also recommended that the submission seeking reclassification should be referred to Medsafe's Pharmacovigilance Team so that any adverse reactions from taking paracetamol in combination with phenylephrine could be actively monitored. The intent of the Committee was that this should involve monitoring spontaneous adverse reaction reports only, rather than conducting any specific active post-market monitoring study. From a search of New Zealand's spontaneous reporting database and the global World Health Organisation database, the New Zealand Pharmacovigilance Centre concluded that there was no evidence of a clinically significant drug interaction between paracetamol and phenylephrine from spontaneous adverse reaction reports received in New Zealand and worldwide. Medsafe agreed with this conclusion based on the data currently available.

As with all medicines, Medsafe will continue to monitor the safety of paracetamol and phenylephrine and will reassess the clinical significance of this possible interaction if further data becomes available.

Following publication of the minutes, AFT Pharmaceuticals informed Medsafe that the interaction between paracetamol and phenylephrine as a potential safety issue had now been suggested by three additional studies as well as the single study published by the date of the last meeting. The Committee revisited their recommendation made at the 52^nd meeting in light of these three studies.

Four pre-meeting comments were received during the consultation period. Three supported the Committee's previous recommendation that paracetamol in combination with phenylephrine should not be reclassified for the following reasons:

1. the suggestion that there has been three additional studies was misleading, the study referenced at the last meeting was a Letter to the Editor describing the three studies included in the paper presented at this meeting
2. comments made by the Committee at the last meeting had not been addressed
3. no new data or clinical evidence has been presented to suggest that the risks outweigh the benefits
4. the potential safety issue of this combination is still hypothetical and should be addressed by appropriately designed and powered clinical studies
5. a reclassification to restricted medicine would increase the burden on pharmacists and without any obvious increased risk to be mitigated it was not clear that this was in the interest of public health
6. a large number of products would be affected by the proposed reclassification
7. the Delegate in Australia had decided (March 2015) that the current scheduling of paracetamol in conjunction with phenylephrine remained appropriate.

One pre-meeting comment supported the reclassification proposals and encouraged the Committee to reclassify these medicines in the interests of public safety.

The Committee concluded that the data in the three published studies had been included in the previous submission and that there were no reports worldwide of adverse reactions resulting from the interaction between phenylephrine and paracetamol.

Recommendation

That there should be no change to the current classification of paracetamol in combination with phenylephrine

5.6

Public consultation process

After the closing date for submissions for each meeting, the agenda is published on the Medsafe website. Following publication there is a consultation period of approximately six weeks before the Committee meets to provide an opportunity for interested parties to comment on the proposed agenda items.

A healthcare professional has raised concerns regarding the effectiveness of the Committee's consultation process and whether the opportunity to comment on agenda items is published widely enough.

The Committee discussed the consultation process, the expectations of the professional bodies in promoting public consultation, and whether any improvements could be made.

The Committee welcomed any suggestions from the sector on improving the consultation process. Only one pre-meeting comment was received during the consultation process which described the public consultation process as opaque and complicated. It also suggested that the current process was not robust and presented a high risk of decisions that favoured industry rather than public interest. No suggestions for improvements were received.

The Secretariat explained that Medsafe has a weekly email service which interested parties can subscribe to. This short weekly email advises when the Medsafe website is updated and notifies parties of key events such as the release of the agenda. There are currently 1,835 recipients of this weekly email service. In addition, the Secretariat has a list of 13 professional organisations and government agencies that are emailed alerting them that the agenda had been published. These organisations and agencies are expected to ensure their members are informed of items of interest on an agenda and that their submissions commenting on agenda items truly reflect the position of their members.

The Committee noted the process followed and raised the possibility of publishing the agenda or a notice that the agenda has been published for an upcoming meeting in Pharmacy Today and NZ Doctor to widen communication.

Recommendation

That Medsafe should explore the possibility of publishing the agenda or a notice about the agenda for upcoming meetings in Pharmacy Today and NZ Doctor.

5.7

Matters arising for information

5.7.1

Classification of ceftolozane, efraloctocog alfa, eftrenonacog alfa, ibrutinib and selexipag

An out-of-session consultation took place in January 2015 regarding the classification of ceftolozane, efraloctocog alfa, eftrenonacog alfa, ibrutinib and selexipag.

The Committee recommended that ceftolozane, ibrutinib and selexipag should be classified as prescription medicines, and that efraloctocog alfa and eftrenonacog alfa should be available as general sale medicines.

These classification recommendations were gazetted on 19 February 2015.

5.7.2

An update on the reclassification of sildenafil
(Silvasta, Douglas Pharmaceuticals Limited)

At the 51^st meeting on 8 April 2014, the Committee recommended 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
• the screening tool should require pharmacists to contact the patient's general practitioner, with the option for the patient to opt-out
• if unhappy with the proposed amendments, the company should be offered the opportunity to withdraw their application.

The Chair provided the Committee with an update on the reclassification of sildenafil.

On 16 October 2014, sildenafil was reclassified as a prescription medicine except in medicines for oral use containing 100 mg or less per dose unit when sold in the manufacturer's original pack containing not more than 12 solid dosage units for the treatment of erectile dysfunction in males aged 35-70 years by a registered pharmacist who has successfully completed a training programme endorsed by the Pharmaceutical Society of New Zealand.

Following the reclassification, Douglas Pharmaceuticals Limited and subsequently Pfizer New Zealand Limited have had training programmes endorsed by the Pharmaceutical Society of New Zealand. The Committee noted that following discussion with the Pharmaceutical Society, the training requirements for both brands of sildenafil had been aligned.

The Committee discussed the timely need for further consideration regarding who is responsible for pharmacist training programmes and suggested that a range of organisations should be involved in these discussions, including the Committee.

5.7.3

Suggested guidance on training materials included in a submission for reclassification

At the 52^nd meeting on 21 October 2014, the Committee recommended that the Chair should write to the Medical Council of New Zealand and the Pharmacy Council of New Zealand suggesting a meeting to discuss the training materials in a submission for reclassification.

The Chair updated Committee members on the outcomes of the meetings he has had with both Councils. In line with the comments made by the Committee under agenda item 5.7.2, the Chair would keep momentum with these discussions.

6

Submissions for reclassification

6.1

Nitrofurantoin – proposed reclassification from prescription medicine to restricted medicine
(Green Cross Health Limited)

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

Purpose

This was a submission for the reclassification of nitrofurantoin from prescription medicine to restricted medicine in medicines for oral use containing 50 mg or less per dose unit when sold in a pack of 20 solid dosage units to a woman aged 16-65 years for the treatment of an uncomplicated urinary tract infection by a registered pharmacist who has successfully completed the New Zealand College of Pharmacists' training in the treatment of urinary tract infections, where supply adheres to the screening tools approved by the Pharmaceutical Society of New Zealand.

The submission proposed that nitrofurantoin should be supplied according to New Zealand's Best Practice Advisory Centre guidelines for uncomplicated urinary tract infection which currently recommends 50 mg four times daily for five days.

The submission also proposed the reclassification would require that the pharmacist had undergone the training required to be able to supply trimethoprim. It was proposed not to make further training mandatory, as pharmacists have a professional obligation as outlined in ethical conduct requirement clauses of the New Zealand Pharmacy Council to remain up to date. However, training around nitrofurantoin specific to the reclassification would be available to pharmacists and it was expected that most pharmacists would complete the training.

The Committee noted there was one product currently marketed that could be affected by the reclassification.

Background

At the 7^th meeting on 31 July and 1 August 1990, the Committee confirmed that nitrofurantoin was classified as a prescription medicine.

Nitrofurantoin is currently classified as a prescription medicine.

Comments

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

Five pre-meeting comments supported the reclassification proposal. Comments in support of the reclassification proposal could be summarised into the following themes:

1. community need in rural areas
2. reclassification of trimethoprim to allow supply by pharmacists has proven to be successful
3. it would provide an alternative treatment to trimethoprim
4. pharmacists should already be well versed in the risks and benefits profile of nitrofurantoin
5. upper age limit should be increased to 70 years
6. the role of the pharmacist in the primary healthcare team would lead to increased collaboration with general practice and other providers.

One pre-meeting comment supported the reclassification proposal in principle. However, the Committee should consider the following:

1. frequency of supply because regular, intermittent use of nitrofurantoin increases the risk of hypersensitivity reactions which may manifest particularly as acute pulmonary reactions
2. providing nitrofurantoin in an approved pack with a compulsory patient information leaflet that has been user-tested to ensure comprehension
3. consumers should be provided with adequate, understandable information to alert them to these potential reactions and what to do should they experience relevant symptoms
4. information should be included that symptoms can also occur after nitrofurantoin has been stopped or the course of treatment completed
5. written information should be mandatory when supplying this antibiotic.

Four pre-meeting comments did not support the reclassification proposal. Comments in opposition of the reclassification proposal could be summarised into the following themes:

1. resistance profile of nitrofurantoin to bacteria causing acute urinary tract infection
2. issue of acute pulmonary reactions
3. unnecessary use of nitrofurantoin may be compounded if the reclassification proposal is successful
4. misdiagnosis
5. fragmentation of care
6. nitrofurantoin is unsuitable for short-term treatment
7. separation of prescribing and dispensing
8. lack of a mandatory requirement for training, adherence to protocols or provision of a private area for consultation.

Discussion

The emergence of microbial resistance to trimethoprim in New Zealand was discussed. Microbial resistance patterns differed across regions in New Zealand. Both trimethoprim and nitrofurantoin are recommended as empiric first line treatment for lower urinary tract infections. However, nitrofurantoin is more likely to be considered for patients when trimethoprim is not suitable or for patients who are more likely to be trimethoprim resistant. Nitrofurantoin has less microbial resistance due to the nature of its mode of action. It was suggested that any future changes in resistance profiles of the region to be included in pharmacist training updates.

The Committee noted that this application was intended to allow a relatively small number of women who had had antibiotics, including trimethoprim, in the past six months to obtain access to an effective antibiotic. The six month antibiotic free period specified in the approved trimethoprim training protocol for pharmacists is not supported by current clinical practice or by other guideline documents on managing simple symptomatic urinary tract infection.

The Committee1s main concern regarded the potential for a hypersensitivity reaction to nitrofurantoin. The Centre for Adverse Reactions Monitoring (CARM) data suggested sensitisation to nitrofurantoin can occur following exposure to a single dose and hypersensitivity reactions can occur during subsequent exposure to nitrofurantoin. The CARM submission also noted that onset of hypersensitivity symptoms can be delayed for up to one week following the discontinuation of nitrofurantoin.

The Committee noted however that other over-the-counter medicines also have a risk of hypersensitivity and that the decision to allow these products to remain available was based on their overall risk-benefit.

The Committee discussed in depth the comments made regarding unnecessary use of nitrofurantoin, misdiagnosis by a pharmacist, fragmentation of care, the separation of prescribing and dispensing and the suggestion that nitrofurantoin is unsuitable for short-term treatment.

Other factors considered by the Committee included the need to know the renal function of a patient in order to use nitrofurantoin safely. Many, although not all, pharmacists have access to patient renal function information. During its discussions, the Committee noted that renal function decreased with age and considered whether the upper age limit for use of nitrofurantoin in the application could be increased to 70 years of age. Due to the evidence that adverse effects of nitrofurantoin increased with dose and the concentration of the antibiotic in the blood, and that plasma concentrations increase as the creatinine clearance falls, the Committee agreed that 65 years old would be a more suitable upper age limit should a reclassification occur.

The Committee highlighted the published evidence demonstrates that adherence to medicines taken four times daily, the current dosing frequency of nitrofurantoin, is generally poor. They questioned whether this could be exacerbated if nitrofurantoin was reclassified as a restricted medicine which would in turn reduce the population benefit of the medicine.

In conclusion, the Committee did not support the reclassification of nitrofurantoin. The benefit of having an alternative to trimethoprim available at pharmacy level did not outweigh the associated risks of hypersensitivity and added complexity of using the medicine.

It was agreed that the current criteria for trimethoprim supply from a pharmacist should be revised, specifically the criteria for women to have had no antibiotics in the previous six months should be removed. Medsafe should write to the New Zealand College of Pharmacists', who provide the training in the treatment of urinary tract infections, with the Committee's recommendation that the criteria for trimethoprim supply by a pharmacist be revised. It should be noted however that these criteria are not part of classification, the criteria are part of the training and as such self-imposed by the industry.

Recommendation

That nitrofurantoin should not be reclassified from prescription medicine to restricted medicine in medicines for oral use containing 50 mg or less per dose unit when sold in a pack of 20 solid dosage units to a woman aged 16-65 years for the treatment of an uncomplicated urinary tract infection by a registered pharmacist who has successfully completed the New Zealand College of Pharmacists' training in the treatment of urinary tract infections, where supply adheres to the screening tools approved by the Pharmaceutical Society of New Zealand.

That Medsafe should write to the New Zealand College of Pharmacists' with the Committee's recommendation that the criteria for trimethoprim supply by a pharmacist be revised, specifically the exclusion criteria of women having used antibiotics in the previous six months should be removed.

6.2

Oral contraceptives – proposed reclassification from prescription medicine to restricted medicine
(Green Cross Health Limited)

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

Purpose

This was a submission for the reclassification of selected oral contraceptives (ethinylestradiol with norethisterone, ethinylestradiol with levonorgestrel, norethisterone, levonorgestrel and desogestrel) from prescription medicine to restricted medicine when supplied for oral contraception by a registered pharmacist who has successfully completed a training course for the supply of oral contraceptives in accordance with the approved protocol for supply.

A strength limit of 35 mcg or less of ethinylestradiol was proposed for oral contraceptives to be included in the proposed reclassification. Although products containing higher doses are available for contraception, it is accepted that these should only be prescribed by an authorised prescriber.

The Committee noted there were twenty-three products currently approved that could be affected by the reclassification.

Background

At the 7^th meeting on 31 July and 1 August 1990, the Committee confirmed that desogestrel, ethinylestradiol, levonorgestrel and norethisterone were all classified as prescription medicines.

At the 14th meeting on 2 November 1994, the Committee considered the safety issues related to the use 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. At the time several studies claimed that low dose oral contraceptive pills containing desogestrel and gestodene presented an increased risk of thromboembolism compared to other low dose oral contraceptive pills.

At the 51^st meeting on 8 April 2014, the Committee recommended that desogestrel, ethinylestradiol, levonorgestrel, and norethisterone should not be reclassified from their current schedule entries.

Desogestrel, ethinylestradiol and norethisterone are currently classified as prescription medicines. Levonorgestrel is currently classified as:

• prescription medicine; except when specified elsewhere in this Schedule; except in medicines for use as emergency post-coital contraception when sold by nurses recognised by their professional body as having competency in the field of sexual and reproductive health
• 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.

This submission included consideration of the specific points raised by the Committee at the 51^st meeting. Each concern raised by the Committee was addressed. The submission argued that the model of care it proposed had now been reviewed by primary healthcare professionals and a more conservative approach had been taken.

Comments

A total of 13 pre-meeting comments were received during the consultation period.

Eight submissions supported the reclassification proposal. Comments in support of the reclassification proposal could be summarised into the following themes:

1. community need in rural areas
2. reduces demand on already stretched general practitioners
3. oral contraceptives are already available over-the-counter overseas
4. pharmacist training should mitigate any risks
5. women will continue to seek out care for cervical screening and sexually transmitted diseases
6. the role of the pharmacist in the primary healthcare team would lead to increased collaboration with general practice and other providers
7. there is a growing body of evidence indicating that women can safely use oral contraceptives obtained without a prescription
8. pharmacists have supplied the emergency contraceptive pill safely for many years.

Five submissions did not support the reclassification proposal. Comments in opposition of the reclassification proposal could be summarised into the following themes:

1. inability to provide continuity of care
2. fragmentation of care
3. general practitioners can offer other forms of contraception if appropriate and investigate other health issues (eg, sexual health) at the same time (a more holistic approach of care)
4. the current requirement for a prescription is not a barrier to accessing oral contraceptives
5. use of oral contraceptives is not without risks (eg, interactions with other medicines)
6. it will not reduce the cost
7. nurses with prescribing rights would be a better choice
8. pharmacists do not have the same checks and balances in place as doctors and nurses do
9. the underlying motive for the proposal appeared to be boosting retail pharmacy profits rather than improving access.

Discussion

At the Committee's request, representatives from the submitting company were invited to present and discuss their evidence to support the proposed reclassification. Additional points raised by these representatives included polls in New Zealand and Australia showing a preference by some women for improved access to oral contraceptives.

The Committee discussed concerns regarding the amount of pharmacist time required for consultation and that not all pharmacies would be resourced to provide such a service.

The concern was also raised that pharmacists do not have access to patient's medical records in order to provide appropriate advice. Although recent innovations in electronic data sharing between health providers (such as HealthOne in Canterbury) would assist in this regard, the Committee noted national adoption of such data sharing was still some way off. Formal consent would be required before the pharmacist could inform the woman's general practitioner that an oral contraceptive had been supplied, potentially resulting in incomplete or disjointed medical records. The Committee acknowledged this is the current situation with existing providers of contraception such as Family Planning and there is no evidence of harm from this.

The Committee considered the application in the context of the requirements of younger women and those from lower socio-economic groups who may not have a general practitioner.

In these scenarios, the Committee considered that reclassification could increase the risk of fragmentation of patient care. However the use of electronic medical records in the future could help to mitigate this risk.

The Committee also noted from the pre-meeting comments that there were a number of possible alternates to this submission that could improve patient access to oral contraceptives including prescribing by practice nurses rather than direct supply by pharmacists, and pharmacist supply by way of standing orders issued by medical practitioners.

The Committee noted that while consultation with some primary healthcare practitioners had occurred it did not consider this consultation to be sufficient and had not met the requirement for resubmission previously set down by the Committee as described in the minutes of the 51^st meeting. After considerable discussion and debate, the Committee resolved that in the absence of support from the major medical representative bodies it could not support this request for reclassification.

The Committee noted that most of the specialist organisations canvassed were in support of a collaborativeprescribing model.

Recommendation

That the selected oral contraceptives (ethinylestradiol with norethisterone, ethinylestradiol with levonorgestrel, norethisterone, levonorgestrel and desogestrel) should not be reclassified from prescription medicine to restricted medicine when supplied for oral contraception by a registered pharmacist who has successfully completed a training course for the supply of oral contraceptives in accordance with the approved protocol for supply.

7

New medicines for classification

7.1

Bilastine - proposed classification as a pharmacy-only medicine
(Labixten, Te Arai BioFarma Limited)

Purpose

This was a company submission for the classification of bilastine as a pharmacy-only medicine in tablets containing 20 mg or less, when sold in a pack containing not more than 30 tablets, for the treatment of the symptoms of allergic rhinoconjunctivitis (seasonal and perennial) and urticaria.

Background

Bilastine is not currently classified and has not been considered by the Committee previously.

Comments

One pre-meeting comment was received during the consultation period which supported the proposed classification of pharmacy-only medicine. One major review published recently concluded that bilastine had comparative efficacy and tolerability to other second-generation antihistamines used as active comparators in phase III trials. Bilastine may also have advantages over cetirizine in having a significantly lower incidence of somnolence.

Discussion

Bilastine is a relatively new second generation antihistamine with moderate to high affinity to the H₁ receptor. The summary data supplied in support of the application suggested bilastine was non-inferior to other second generation antihistamines, desloratadine and loratadine.

The Committee noted that in the data presented, the clinical and adverse effects associated with bilastine are similar to other second generation antihistamines.

Recommendation

That bilastine should be classified as a prescription medicine, except when specified elsewhere in this Schedule.

That bilastine should be classified as a pharmacy-only medicine in tablets containing 20 mg or less, when sold in a pack containing not more than 30 tablets, for the treatment of the symptoms of allergic rhinoconjunctivitis (seasonal and perennial) and urticaria.

7.2

Otilonium bromide - proposed classification as a restricted medicine
(Menoctyl, Te Arai BioFarma Limited)

Purpose

This was a company submission for the classification of otilonium bromide as a restricted medicine in tablets containing 40 mg or less, when sold in a pack containing not more than 30 tablets, for the symptomatic treatment of irritable bowel syndrome and painful, spastic conditions of the distal enteric tract (colon and rectum), and for the relief of abdominal pain, distension and motility disorders in patients older than 18 years of age caused by smooth muscle spasm of distal parts of the intestinal tract.

The submission proposed that treatment recommendations made by a pharmacist would be aided by training material and regulatory support provided by Te Arai BioFarma Limited.

Background

Otilonium bromide is not currently classified and has not been considered by the Committee previously.

Comments

Two pre-meeting comments were received during the consultation period. Both supported the classification proposal. Community pharmacists currently have limited ability to provide adequate treatment for patients who commonly present in pharmacies requiring acute treatment of symptoms associated with irritable bowel syndrome. Pharmacists are ethically bound to learn about new medicines as they become available on the New Zealand market and only recommend a medicine that they have the appropriate level of knowledge about. The training material suggested in the submission would facilitate the upskilling of pharmacists.

Discussion

The Committee noted that otilonium bromide is not registered in Australia, Canada or the United Kingdom. In other countries it is classified as a prescription medicine. It was also noted that many of the countries where it is registered have no restricted medicine classification.

Otilonium bromide is a member of the quaternary ammonium derivative class of compounds and acts as a topical intestinal antispasmodic. It shows specificity for the smooth muscle of the colon and rectum at therapeutic concentrations, having a local action with negligible systemic absorption. It is largely excreted unmetabolised in the faeces. The duration of treatment is not well defined and the proposed pack size does not relate to the recommended dosage regimen.

The Committee was concerned that there is no experience with use of this medicine in New Zealand and raised questions about the ability to appropriately diagnose irritable bowel syndrome in the pharmacy. There is the potential risk that patient self-diagnosis and differential diagnosis by a pharmacist is not able to exclude and / or identify other more serious diseases such as bowel cancer.

Recommendation

That otilonium bromide should be classified as a prescription medicine.

7.3

Racetams - proposed classification as prescription medicines

The Ministry of Health had received numerous queries regarding the regulatory position of cognitive enhancing products containing a group of compounds known collectively as racetams or racetam-like substances, and whether there should be restrictions on their importation into New Zealand.

The Medsafe submission noted that the nootropic (and other therapeutic) claims associated with the racetam class of substances, were sufficient under the Medicines Act 1981 to regard this class of substance as medicines. In addition, classifying them as prescription medicines would be consistent with the regulation of piracetam and levetiracetam, two racetams registered as medicines that are currently classified as prescription medicines.

The submission noted that classification of the racetam class of substances would also mean access to the substances could be controlled and would reduce the risk of harm occurring to consumers due to inappropriate use.

Given the inability to create a class entry for racetams the submission requested the Committee consider classifying each individual substance known at this time to be marketed as a nootropic agent as a prescription medicine.

No comments were received during the consultation period.

Discussion

The Committee agreed that there is no suitable class entry that will describe all of the concerned racetam and racetam-like structures, and that classifying them individually as prescription medicines was most appropriate.

Recommendation

That the following racetam and racetam-like substances should be classified as prescription medicines: aloracetam, aniracetam, brivaracetam (and its stereoisomers), cebaracetam (and its stereoisomers), coluracetam, dimiracetam (and its stereoisomers), doliracetam (and its stereoisomers), dupracetam, etiracetam, fasoracetam (and its stereoisomers), fonturacetam (and its stereoisomers), imuracetam, molracetam, nebracetam (and its stereoisomers), nefiracetam, nicoracetam, noopept (and its stereoisomers), oxiracetam (and its stereoisomers), piperacetam, pramiracetam, rolipram (and its stereoisomers), rolziracetam, seletracetam (and its stereoisomers).

7.4

New chemical entities

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

7.4.1

Elosulfase alfa - Vimizim 1 mg/mL solution for infusion

Vimizim is a formulation of elosulfase alfa, which is a purified human enzyme produced by recombinant DNA technology in a Chinese hamster ovary cell line.

Vimizim is proposed to be indicated for the treatment of mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).

Elosulfase alfa is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That elosulfase alfa should be classified as a prescription medicine.

7.4.2

Fomepizole - Antizol 1 g/mL intravenous infusion

Antizol (fomepizole) is a competitive inhibitor of alcohol dehydrogenase. Alcohol dehydrogenase catalyses the oxidation of ethanol to acetaldehyde. Alcohol dehydrogenase also catalyses the initial steps in the metabolism of ethylene glycol and methanol to their toxic metabolites. Treatment of ethylene glycol and methanol poisonings consist of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as Antizol (fomepizole).

Antizol (fomepizole) injection is proposed to be indicated as an antidote for ethylene glycol (such as antifreeze) or methanol poisoning (such as windshield washer fluid), or for use in suspected ethylene glycol or methanol ingestion, either alone or in combination with haemodialysis.

Fomepizole is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That fomepizole should be classified as a prescription medicine.

7.4.3

Idarucizumab - Praxbind 50 mg/mL solution for injection

Idarucizumab is a humanised monoclonal antibody fragment molecule derived from an IgG1 isotype antibody molecule, directed against the thrombin inhibitor dabigatran.

Praxbind is a specific reversal agent for dabigatran and is proposed to be indicated in patients treated with Pradaxa when rapid reversal of the anticoagulant effects of dabigatran is required:

• for emergency surgery / urgent procedures
• in life-threatening or uncontrolled bleeding.

Idarucizumab is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That idarucizumab should be classified as a prescription medicine.

7.4.4

Idelalisib - Zydelig 100 mg and 150 mg film coated tablets

Zydelig is the brand name for idelalisib, an isoform-selective, small-molecule inhibitor of phosphatidylinositol 3-kinase p110δ (PI3Kδ).

Zydelig in combination with rituximab is proposed to be indicated for the treatment of patients with chronic lymphocytic leukaemia / small lymphocytic lymphoma for whom chemo-immunotherapy is not considered suitable, either:

• Upon relapse after at least one prior therapy, or
• as first-line treatment in the presence of 17p deletion or TP53 mutation.

Zydelig is proposed to be indicated as monotherapy for the treatment of patients with refractory follicular lymphoma who have received at least two prior systemic therapies.

Idelalisib is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That idelalisib should be classified as a prescription medicine.

7.4.5

Peginterferon beta-1a - Plegridy 125 µg/0.5 mL solution for injection (admin pack and titration pack

Peginterferon beta-1a (rch) is recombinant interferon beta-1a conjugated to 20 kDa methoxy poly(ethylene glycol) using an -O-2-methylpropionaldehyde linker. It is expressed in mammalian cells and has the same sequence as naturally-occurring human interferon beta. The 20 kDa mPEG-O-2-methylpropionaldehyde is attached to the α-amino group of the N-terminal amino acid residue using reductive amination chemistry.

Plegridy is proposed to be indicated for the treatment of relapsing forms of multiple sclerosis.

Peginterferon is already classified as a prescription medicine in New Zealand and Australia.

Peginterferon beta-1a is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That peginterferon beta-1a should be classified as a prescription medicine.

7.4.6

Pembrolizumab - Keytruda powder for solution for infusion

One vial contains 50 mg of pembrolizumab.

After reconstitution, 1 mL of solution contains 25 mg of pembrolizumab.

Keytruda (pembrolizumab) is a selective humanized monoclonal antibody designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Pembrolizumab is an IgG4 kappa immunoglobulin with an approximate molecular weight of 149 kDa. Pembrolizumab is produced in Chinese hamster ovary cells by recombinant DNA technology.

Keytruda (pembrolizumab) is proposed to be indicated as monotherapy for the treatment of unresectable or metastatic melanoma in adults.

Pembrolizumab is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That pembrolizumab should be classified as a prescription medicine.

7.4.7

Pirfenidone

Anecdotal evidence suggests that a number people in Auckland are importing pirfenidone for personal use. Customs cannot prevent importation because pirfenidone is not classified in New Zealand.

Pirfenidone is proposed to be indicated in adults for the treatment of mild to moderate Idiopathic Pulmonary Fibrosis.

Pirfenidone is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015). Pirfenidone is classified as a prescription only medicine in Europe.

Recommendation

That pirfenidone should be classified as a prescription medicine.

7.4.8

Ranolazine - Ranexa 375 mg, 500 mg and 750 mg modified release tablets

Ranexa is proposed to be indicated in adults as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as beta-blockers and / or calcium antagonists).

Ranolazine is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That ranolazine should be classified as a prescription medicine.

7.4.9

Recombinant human Epidermal Growth Factor - Heberprot-P 75 µg powder for injection

Heberprot-P is a lyophilized product for parenteral administration by intralesional route. The drug substance is the recombinant human Epidermal Growth Factor and the excipients are sucrose and dextran 40 in sodium phosphate buffer solution.

Heberprot-P is proposed to be indicated for the healing of diabetic foot ulcers with deep neuropathic and / or ischemic wound with area above 1 sq.cm, reaching tendons, ligaments, joints or bones; and to reduce the risk of lower limb amputation.

Recombinant human Epidermal Growth Factor is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That recombinant human Epidermal Growth Factor should be classified as a prescription medicine.

7.4.10

Secukinumab - Cosentyx 150 mg powder for injection and 150 mg/mL solution for injection

Secukinumab is a recombinant fully human monoclonal antibody selective for interleukin-17A. Secukinumab is of the IgG1/κ-class produced in Chinese hamster ovary (CHO) cells.

Cosentyx is proposed to be indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.

Secukinumab is not scheduled in Australia in the Standard for the Uniform Scheduling of Medicines and Poisons (No.6, Poisons Standard 2015).

Recommendation

That secukinumab should be classified as a prescription medicine.

7.4.11

Simoctocog alfa - Nuwiq 250 IU, 500 IU, 1000 IU and 2000 IU powder for injection

Nuwiq contains simoctocog alfa (human coagulation factor VIII (rDNA)) which is a purified protein that has 1440 amino acids. The amino acid sequence is comparable to the 90 + 80 kDa form of human plasma factor VIII (ie, B-domain deleted). Human-cl rhFVIII is produced by recombinant DNA technology in genetically modified human embryonic kidney (HEK) 293F cells. No animal or human derived materials are added during the manufacturing process or to the final medicinal product. Post-translational modifications of Human-cl rhFVIII are similar to endogenous human coagulation factor VIII of healthy subjects, and thus antigenic carbohydrate epitopes, as described for recombinant factor VIII expressed in hamster cell lines, are not present.

Nuwiq is proposed to be indicated for the treatment and prophylaxis of bleeding (also during and after surgery) in previously treated paediatric (≥ 2 years) and adult patients with haemophilia A congenital factor VIII deficiency.

Nuwiq does not contain von Willebrand Factor and is thus not proposed to be indicated to treat von Willebrand's Disease.

Blood clotting factors, blood corpuscles and whole blood are available as general sale medicines in New Zealand.

In October 2014 the Delegate in Australia made a final decision that simoctocog alfa falls under Appendix A - General Exemptions under Human Blood Products as it is an equivalent recombinant alternative to a plasma-derived clotting factor.

Recommendation

That simoctocog alfa should be available as a general sale medicine.

8

Harmonisation of the New Zealand and Australian schedules

8.1

New chemical entities which are not yet classified in New Zealand

8.1.1

Bosutinib

In October 2014, the Delegate made a final decision to include bosutinib in Schedule 4 (prescription medicine), with an implementation date of 1 February 2015, for the following reasons:

1. it is a new chemical entity with limited clinical experience in Australia - the Therapeutic Goods Agency has found a positive benefit-risk balance for bosutinib for specific uses
2. recommended use is limited to specified haemato-oncology indications
3. toxicity has been factored into the Therapeutic Goods Agency's appraisal of benefit-risk balance and is consistent with Schedule 4 scheduling
4. these factors have been considered in the Therapeutic Goods Agency's appraisal of benefit-risk balance and are consistent with Schedule 4 scheduling
5. the potential for abuse of bosutinib is unlikely.

Recommendation

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

8.1.2

Brentuximab vedotin

In October 2014, the Delegate made a final decision to include brentuximab vedotin in Schedule 4 (prescription medicine), with an implementation date of 1 February 2015, for the following reasons:

1. it is a new chemical entity with limited clinical experience in Australia - the Therapeutic Goods Agency has found a positive benefit-risk balance for brentuximab vedotin for specific uses
2. recommended use is limited to specified haemato-oncology indications
3. toxicity has been factored into the Therapeutic Goods Agency's appraisal of benefit-risk balance and is consistent with Schedule 4 scheduling
4. these factors have been considered in the Therapeutic Goods Agency's appraisal of benefit-risk balance and are consistent with Schedule 4 scheduling
5. the potential for abuse of brentuximab vedotin is unlikely.

Recommendation

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

8.1.3

Carglumic acid

In October 2014, the Delegate made a final decision to include carglumic acid in Schedule 4 (prescription medicine), with an implementation date of 1 February 2015, for the following reasons:

1. it is a new chemical entity with no clinical / marketing experience in Australia
2. the proposed therapeutic use relates to conditions requiring specialist care including acute care settings.

Recommendation

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

8.1.4

Suvorexant

In October 2014, the Delegate made a final decision to include suvorexant in Schedule 4 (prescription medicine), with an implementation date of 1 February 2015, for the following reasons:

1. suvorexant is a new chemical entity with no clinical or marketing experience in Australia
2. the substance is intended to cause drowsiness and its effects are additive with alcohol.

Suvorexant is a dual orexin receptor antagonist. Suvorexant was proposed to be indicated for the treatment of insomnia, characterised by difficulties with sleep onset and / or sleep maintenance.

Recommendation

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

8.2

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

The Committee noted that the Delegate had also made the following amendments to the Standard for the Uniform Scheduling of Medicines and Poisons:

1. bendamustine - should be included in Schedule 4 (prescription medicine) which harmonised with New Zealand
2. macitentan - should be included in Schedule 4 (prescription medicine) which harmonised with New Zealand.

8.2.1

Decisions by the Delegate - October 2014

Decisions included under agenda item 8.1.

8.3

Harmonisation recommendations made at the 52^nd meeting

8.3.1

Macrogols

Macrogols, in oral preparations for bowel cleansing prior to diagnostic, medical or surgical procedures, are currently classified as restricted medicines in New Zealand. This classification followed a recommendation by the Committee at its 24^th meeting on 2 November 2000.

At the 30^th meeting on 26 November 2003, the Committee recommended that macrogols should remain unscheduled for laxative use. Macrogols are currently available as general sale medicines for laxative use.

At the 52^nd meeting on 21 October 2014, the Committee recommended that:

1. a new pharmacy-only medicine entry should not be created for macrogols in preparations for oral use as a liquid concentrate for laxative use
2. the Scheduling Secretariat in Australia should be asked for further information on why the Delegate decided to include a new Schedule 2 (pharmacy-only medicine) entry should be created for macrogols in preparations for oral use as a liquid concentrate for laxative use.

The Committee reconsidered a pharmacy-only entry for macrogols now that further information had been provided by the Scheduling Secretariat in Australia. This information noted that macrogols were now being promoted and sold as laxatives for routine use. The Advisory Committee on Medicines Scheduling in Australia expressed concerns about the potential abuse of macrogol laxatives and recommended that they be reclassified.

The Committee noted there were nine products currently marketed that could be affected by a recommendation to reclassify.

The Committee agreed to harmonise with Australia and that macrogols for laxative use should be reclassified to pharmacy-only medicines.

Recommendation

That macrogols should be reclassified from general sale medicines to pharmacy-only medicines when used as laxatives.

9

Agenda items for the next meeting

No items were added to the agenda at this point in time.

10

General business

10.1

New Zealand's domestic regulatory reform

An update was provided following the announcement that the Australian and New Zealand Governments have agreed to cease efforts to establish a joint therapeutic products regulator (the Australia New Zealand Therapeutic Products Agency (ANZTPA)).

10.2

Articles for information

The Committee was presented with the following article for information:

1. Gauld NJ, Kelly FS, Kurosawa N, et al. 2014. Widening consumer access to medicines through switching medicines to non-prescription: A six country comparison. PLOS One. URL http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0107726 (accessed 7 April 2015).

11

Date of next meeting

To take place on a Tuesday in October 2015. The Secretary would email members for their availability.