1

WELCOME

The Chair opened the 42^nd meeting at 9:30am and welcomed members and guests. The Chair explained that Mr Orange, who was observing the meeting, would be replacing Ms Gauld on the Committee early next year.

2

APOLOGIES

Apologies were received from Dr Copland, whose apology was a result of illness in transit to the meeting, and Dr Galler.

Dr Lopert was only present, via telephone, for Agenda Item 5.2. Mrs Miller joined the meeting for Agenda Items 5.2 and 5.8. Ms Firth joined the meeting for Agenda Item 5.8 only.

3

CONFIRMATION OF THE MINUTES OF THE 41^ST MEETING HELD ON THURSDAY 14 MAY 2009

The minutes of the 41^st meeting were accepted as a true and accurate record. The minutes were signed and dated by the Chair.

4

DECLARATION OF CONFLICTS OF INTEREST

The Conflict of Interest forms were returned to the Secretary. All but one of the members declared they had no interests which would pose a conflict with any of the items on the agenda.

That member declared they had been contracted by the College of Pharmacists to speak at three College meetings regarding omeprazole for pharmacist education. These meetings were sponsored by Bayer New Zealand so could be perceived as a conflict of interest with the reclassification of omeprazole 20 mg tablets on the current agenda. The declaration was discussed in the absence of that member. The Committee agreed the member could participate in the discussion but not vote.

The same member also declared they had received payment for providing Janssen-Cilag professional advice on a prescription product unrelated to any over-the-counter products. As Janssen-Cilag is a Johnson & Johnson company, this could be perceived as a conflict of interest with the reclassification of codeine on the current agenda with respect to cough and cold remedies. The declaration was also discussed in the absence of that member. The Committee agreed the declaration was sufficient; the member could participate fully in the discussion.

5

MATTERS ARISING

5.1

Amyl Nitrite

Amyl nitrite is classified as a prescription medicine, except when sold from outlets licensed to sell cyanide paste for the purpose of vertebrate pest control.

It had been brought to Medsafe's attention that the wording of the exception needed updating to more clearly reflect the requirements of the Agricultural Compounds and Veterinary Medicines Act 1997. It was no longer outlets that were licensed to sell cyanide, but the Environmental Risk Management Authority licensed persons by way of a controlled substances license. Following external advice, Medsafe proposed that the amyl nitrite Schedule entry be amended to prescription medicine, except when sold in circumstances complying with any regulations or conditions imposed under the Agricultural Compounds and Veterinary Medicines Act 1997 in respect of the sale of cyanide paste.

The revised wording did not alter the level of access currently allowed for amyl nitrite.

An interested body had commented they believed the wording proposed in the agenda did not adequately describe the conditions under which cyanide paste may be sold for the purposes of pest control. The proposed wording had taken into account the registration of cyanide preparations under the Agricultural Compounds and Veterinary Medicines Act 1997. However, it had been strongly recommended that the wording be amended to include a reference to the Hazardous Substances and New Organisms Act 1996. The interested body highlighted the proposed wording needed to describe the requirements under which cyanide paste, and thus the co-sale of amyl nitrite, could be sold.

The Committee agreed that the wording of the exception should be amended to include a reference to the Hazardous Substances and New Organisms Act 1996. It was agreed that Medsafe should seek advice from the Environmental Risk Management Authority and amend the wording to reflect this advice. Medsafe would proceed to Gazette this revised wording.

Recommendation

That Medsafe should seek advice from the Environmental Risk Management Authority regarding the wording of the exception to the prescription entry in the Schedule for amyl nitrite and amend the wording to reflect that advice. Medsafe would proceed to Gazette this revised wording.

5.2

Codeine

At the 38^th meeting on 14 December 2007 the Committee had been asked to decide whether access to codeine should be further restricted, and whether pack sizes should be limited, in combination products containing increasingly larger doses of codeine.

At the 39^th meeting on 25 June 2008, following consultation with interested bodies, the Committee recommended that combination medicines containing more than 15 mg of codeine per dose unit, and which comply with all other requirements for pharmacy-only sale as specified in Part VI(a) of the Third Schedule to the Misuse of Drugs Act 1975, should be reclassified from pharmacy-only medicines to prescription medicines. This recommendation was put into effect after the 41^st meeting.

Prior to the 40^th meeting, further consultation on codeine was undertaken about suitable cut-off points and pack size limits for pharmacy-only and restricted medicine levels of access, based on the following proposal:

• pharmacy-only combination products should contain 12 mg or less of codeine per dose unit with a maximum recommended treatment period of seven days and an upper pack size limit of 50 dose units
• restricted medicine combination products should contain 15 mg or less but more than 12 mg of codeine per dose unit and an upper pack size limit of 25 dose units
• all combination products containing more than 15 mg of codeine per dose unit should be prescription medicines. Lower pack size limits for prescription medicine classification would be established after upper limits for pharmacy-only and restricted medicines had been finalised.

At the 40^th meeting on 25 November 2008 no recommendation was required from the Committee. The Australian National Drugs and Poisons Schedule Committee (NDPSC) working party on codeine had not yet completed its review of combination codeine products. The Chair said that it was important that New Zealand and Australia should be harmonised in their treatment of these products and hence making a recommendation was postponed until the NDPSC had resolved its own position in regard to the classification of codeine in combination products. The report of the review was now available.

At the 41^st meeting on 14 May 2009, the Committee considered suitable codeine cut-off points and pack sizes for over-the-counter sale. The Committee foreshadowed for consideration at the 42^nd meeting a proposal to reclassify codeine in combination products to either a restricted medicine or a pharmacy-only medicine when:

• each dose unit contains not more than 15 mg of codeine base
• the maximum daily dose is limited to 100 mg of codeine base
• the pack size is not more than five days' supply.

In response to this proposal the Secretariat of the Committee received a total of four pre-meeting comments to be considered at this meeting. These submissions made a number of points:

1. the vast majority of New Zealanders access codeine-combination products in a responsible manner
2. there may be as few as 10 cases of codeine-combination product addicts reported in the last year in New Zealand out of the 2.6 million over-the-counter units purchased
3. evidence presented to date in Australia and New Zealand lead to the conclusion that ibuprofen / codeine combination analgesics and, to some extent paracetamol / codeine analgesics, are the products involved in codeine abuse, as opposed to cough and cold tablets that contain codeine
4. there does not seem to be any evidence that pharmacy-only cough and cold tablets with phenylephrine / codeine combinations are unsafe given the data available
5. cough and cold products containing codeine should be separated from analgesic / codeine rescheduling considerations
6. there is no research to show that restricting access will have any impact on the problem of addiction or abuse
7. a proposed solution included the introduction of an online monitoring system for sales and allowing the Code of Ethics (advice for pharmacy from the professional bodies in dealing with the sale of products of potential misuse and abuse) to gain traction
8. pharmacists already have the ability to manage sales of misused products and this is effectively policed.

All four pre-meeting comments concluded there should be no change to the current Schedule. However, if there was to be a scheduling change, the following workable solutions were suggested:

Solution A

• Pharmacy-only classification for codeine combination products with 12 mg or below of codeine base as a unit dose to a maximum 100 mg daily dose and seven days' supply.
• Restricted classification for up to 15 mg of codeine base as a unit dose with a maximum 100 mg daily dose and more than seven days supply but with a maximum pack size of a 100 tablets.
• Prescription status for 15 mg and above of codeine base as a unit dose with no restriction on daily maximum or pack size.

Solution B

• Pharmacy-only classification for codeine combination products with 12 mg or less of codeine base per unit dose to a maximum 100 mg daily dose and an upper pack size limit of 48 dose units.
• Restricted classification for combination codeine products containing up to 15 mg or less but more than 12 mg of codeine base per unit dose with a maximum daily dose of 100 mg; and
• for combination codeine products containing 12 mg or less of codeine base per unit dose to a maximum 100 mg daily dose in pack sizes of greater than 48 dose units.
• Prescription status for combination codeine products containing greater than 15 mg of codeine base as a unit dose.

Solution C

• Pharmacy-only classification for codeine combination products with no more than 12 mg codeine base as a unit dose to a maximum 100 mg daily dose and seven days supply.
• Restricted classification for no more than 15 mg of codeine base as a unit dose with a maximum 100 mg daily dose and more than seven days supply but with a maximum pack size of 100 tablets.
• Prescription classification for more than 15 mg of codeine base as a unit dose with no restriction on daily maximum or pack size.

N.B. In the above solutions 15 mg of codeine phosphate is equivalent to 11.72 mg of codeine base.

Solution D

• Codeine-containing combination medicines in products containing 12 mg or less of codeine per dose unit and in packs containing not more than 100 dose units should be pharmacy-only medicines.

In addition to these four pre-meeting comments the Committee noted that, at their 56^th meeting on 16-17 June 2009, the NDPSC recommended the following amendments to the Australian Schedule:

Schedule 2 (pharmacy-only medicine) - Amendment

Codeine in preparations for the treatment of coughs and colds when:

1. not combined with any other opiate substance;
2. compounded with one or more other therapeutically active substances, of which at least one is phenylephrine and not more than one is an analgesic substance:
   1. in divided preparations containing 10 mg or less of codeine per dosage unit; or
   2. in undivided preparations containing 0.25 per cent or less of codeine;
3. labelled with a recommended daily dose not exceeding 60 mg of codeine; and
4. in packs containing not more than five days of supply at the maximum dose recommended on the label.

Schedule 3 (restricted medicine) - Amendment

Codeine when:

1. not combined with any other opiate substance;
2. compounded with one or more other therapeutically active substances, of which not more than one is an analgesic substance:
   1. in divided preparations containing 12 mg or less of codeine per dosage unit; or
   2. in undivided preparations containing 0.25 per cent or less of codeine; and
3. labelled with a recommended daily dose not exceeding 100 mg of codeine; and
4. in packs containing not more than five days of supply at the maximum dose recommended on the label, except when included in Schedule 2.

The Committee also noted a press release, dated 2 September 2009, from the Medicines and Healthcare products Regulatory Agency in the United Kingdom relating to codeine. This release announced the introduction of new warnings and tighter controls on the sales of over-the counter medicines containing codeine or dihydrocodeine to minimise the risk of their overuse and addiction:

1. indications for codeine or dihydrocodeine containing products limited to the treatment of moderate pain
2. removal of cough and cold symptom relief indication for products containing codeine
3. duration of treatment to be limited to three days due to the risk of addiction
   pack size limit of four days
4. new labelling requirements that codeine is addictive
5. sale to be conducted by pharmacists.

The Committee also noted a recent Scrip News article, dated 10 July 2009. The Food and Drug Administration's expert advisors in the United States have stated prescription products that combine acetaminophen (paracetamol) with opioids or other pain relievers (including codeine) should be eliminated to reduce the risk of liver damage associated with their use.

One member had recently held a discussion with a doctor who worked three days per week in a detoxification unit at the Community Alcohol and Drug Services in Auckland and as a General Practitioner. That doctor estimated the unit observed one new person presenting per week taking more than the recommended amount of over-the-counter codeine containing products, some of whom presented following an adverse event such as gastric bleeding or anaemia resulting from the misuse. When discussing options ahead, the doctor was keen to have limited pack sizes, a warning on the pack regarding both addiction and long term use causing rebound headache, the products behind the counter and training of pharmacists in recognising and managing abuse of these medicines.

The Committee's deliberations centred around three main questions, whether:

1. a dose unit should contain not more than either 15 mg or 12 mg codeine base
2. the pack size should contain five days or seven days as the maximum
3. the reclassification should include codeine-containing cough and cold preparations (such medicines have not been considered separately to date).

The Chair emphasised to the Committee that, with respect to the NDPSC recommendation, the agreed approach for harmonisation was that the countries should harmonise at the lowest schedule unless there were public health reasons not to. The recent decision in the United Kingdom reported by the Medicines and Healthcare products Regulatory Agency could be considered pivotal to the Committee's consideration.

The Committee discussed at length the classification proposal, the risks and benefits of codeine containing products, and what was appropriate risk management to limit the risk of addiction. The pharmacist member noted that in the wide range of pharmacies in which she had worked, medicines that are abused such as cyclizine and stimulant laxatives are usually handled very well, including by pharmacy staff. It was noted that there were instances she was aware of in which the pharmacist discussed the codeine addiction with the consumer and appropriate advice was sought. However, the awareness of this issue in pharmacy, including who is abusing, needed improvement. This pharmacist member suggested, rather than a restricted medicine classification, reducing the pack size and having products classified as pharmacy-only, alongside asking industry and pharmacy organisations to support placing these products out of reach of consumers (behind the counter), would be sufficient to manage the risk of addiction. This member also suggested codeine containing products could, when advertised, include a warning statement that prolonged use could lead to addiction. It was noted that making these products restricted medicines would mean the vast majority of people who were using these medicines without abusing them would have to wait for a pharmacist and have their name and address recorded for each occasion of purchase.

Concerns were expressed about the common medical practice software default to 720 paracetamol and codeine tablets, if prescribed.

The Committee discussed these suggestions and finally agreed, by majority vote, to reclassify codeine in combination products as a restricted medicine when:

• each dose unit contains not more than 15 mg of codeine base
• the maximum daily dose is limited to 100 mg of codeine base
• the pack size is not more than five days' supply
• sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine.

The Committee also concluded that cough and cold preparations containing codeine could be classified as pharmacy-only medicines when:

• each dose unit contains not more than 15 mg of codeine base
• the maximum daily dose is limited to 100 mg of codeine base
• the pack size is not more than six days' supply
• sold in packs approved by the Minister or the Director-General for distribution as a pharmacy-only medicine.

The Committee noted these recommendations could create the situation where those addicted to codeine may try to seek alternative sources of codeine from cough and cold medicines.

Following discussion the Committee agreed that the decision to allow cough and cold preparations containing codeine to continue to be available at the pharmacy-only level should be reviewed in 12-18 months time. In the interim the Committee recommended that Medsafe should write to the Pharmaceutical Society and the Pharmacy Guild explaining that, following the reclassification of codeine in combination analgesic products as restricted medicines, the risk of patients addicted to codeine transferring from analgesics to the cough and cold preparations containing codeine could increase. The letter should request the Pharmacy sector to treat codeine containing cough and cold medicines as potentially addictive medicines and, in keeping with the Pharmacy Council Code of Ethics, require these products be moved behind the counter and not be available for self selection. The letter would also ask pharmacists to warn patients about the risk of addiction to cough and cold preparations. The Committee finally suggested that Medsafe should publish an article on the reclassification of codeine for General Practitioners and pharmacists in Prescriber Update. The article should also advise prescribers and pharmacists to warn patients about the risks of addiction to codeine.

The Committee also discussed the United Kingdom's decision to label codeine containing products with warning statements regarding addiction. The Committee supported the United Kingdom's approach and felt it would further discourage long term use of these products. Medsafe should insert these requirements into the New Zealand Regulatory Guidelines for Medicines.

Recommendation

That codeine in combination products should be reclassified as a restricted medicine when:

• each dose unit contains not more than 15 mg of codeine base
• the maximum daily dose is limited to 100 mg of codeine base
• the pack size is not more than five days' supply
• sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine.

That the decision to allow cough and cold preparations containing codeine to continue to be available at the pharmacy-only level would be reviewed in 12-18 months time.

That Medsafe should write to the Pharmaceutical Society and the Pharmacy Guild regarding the reclassification of codeine in combination products and the recommended reclassification of cough and cold preparations.

That Medsafe should be requested to write an article on the reclassification of codeine for General Practitioners in Prescriber Update.

That Medsafe require codeine containing products to be labelled with warning statements similar to those required in the United Kingdom - "Do not use for more than 3 days" and "Codeine is an addictive substance".

That the requirements for codeine in combination products to be reclassified as a restricted medicine should be inserted into the New Zealand Regulatory Guidelines for Medicines by Medsafe.

5.3

Famciclovir 500 mg tablet
(Famvir, Novartis New Zealand Ltd)

At the 41^st meeting on 14 May 2009 the Committee considered a submission for the reclassification of famciclovir 500 mg tablets from prescription medicine to restricted medicine when sold in packs of three tablets for the treatment of recurrent Herpes labialis (cold sores). The Committee recommended that there should be no change to the current prescription medicine classification. However, the Committee agreed to review the submission if further information was provided. Such information should include warnings and precautions relating to age and to use in patients with diabetes as well as any other training material that would aid in identifying patients who may have impaired renal function or may be immunocompromised. Patient advice should also include information not to repeat treatment within the course of an illness.

The reclassification was reconsidered because the sponsor company had provided additional information in support of the classification change. A treatment algorithm had been developed which was designed to help pharmacists identify patients who might benefit from the appropriate cold sore therapy and to screen out patients who were unsuitable for over-the-counter treatment, for example patients who may have impaired renal function or may be immunocompromised. In addition the company had proposed that the following warning statements be added to the pack:

1. caution: If you have kidney disease check with your doctor or pharmacist before commencing treatment
2. not recommended for patients under 18 years of age.

The revised submission also proposed three other changes:

1. to market the product as Famvir ONCE which would help reinforce the single dose concept
2. to supply every pharmacy with a 'Famvir ONCE Training Kit'
3. to develop patient education material aimed at making patients aware of the optimal time to treat cold sores and to speak to their pharmacist about all treatment options.

The sponsor company also provided information which had also been submitted to the NDPSC for consideration at the October 2009 meeting.

One pre-meeting comment had been received during the consultation period and this was in support of the reclassification of famciclovir 500 mg tablets from prescription medicine to restricted medicine.

The Committee felt that some issues were still outstanding. The treatment algorithm needed elaboration, especially how to check whether a patient was immunocompromised. Extensive use of famciclovir in immunocompromised patients could theoretically lead to the development of resistance.

It was noted that, while pharmacists could not always know if a person had renal impairment as the person may not know themselves, as a single dose given immediately there would not be an accumulation from this drug if there was renal impairment present. Other medicines available without prescription used in multiple doses also have a caution for renal impairment.

The Committee concluded that famciclovir 500 mg tablets could be reclassified from prescription medicine to restricted medicine when sold in packs of three tablets for the treatment of recurrent Herpes labialis (cold sores) provided Medsafe is satisfied that:

• the sponsor company has approached the Pharmaceutical Society requesting their input on the treatment algorithm and implemented any suggested changes required
• a warning that treatment should not be repeated within seven days is included on the label.

Medsafe should insert these requirements into the New Zealand Regulatory Guidelines for Medicines.

Recommendation

That tablets containing 500 mg or less of famciclovir should be reclassified as a restricted medicine when sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine.

That the requirements famciclovir to be reclassified as a restricted medicine should be inserted into the New Zealand Regulatory Guidelines for Medicines by Medsafe.

That Medsafe should be satisfied:

• the sponsor company has approached the Pharmaceutical Society requesting their input on the treatment algorithm and implemented any suggested changes required
• a warning that treatment should not be repeated within seven days is included.

5.4

Heparins

At the 40^th meeting on 25 November 2008 blood and blood products had been recommended for reclassification as general sales medicines with the intention of harmonising with Australia. An unintended consequence of this had recently been identified; some products containing blood clotting factors also contained small amounts of heparin as an excipient. Heparins remain classified as a prescription medicine, thereby preventing these products from being reclassified to general sale as had been the intention.

Medsafe proposed that the Committee discuss exempting heparins from classification as a prescription medicine to general sale medicine when present as an excipient.

It was noted by the Committee that a similar exemption had been used in the past to exempt phenacetin from the Schedule when used as an excipient. Following discussion the Committee agreed that heparins should be classified as:

• prescription medicine; for internal use; except when present as an excipient
• general sale; for external use; when present as an excipient.

Recommendation

That heparins should be classified as:

• prescription medicine; for internal use; except when present as an excipient
• general sale; for external use; when present as an excipient.

5.5

Lansoprazole 15 mg capsule
(Solox, Douglas Pharmaceuticals Ltd)

At the 40^th meeting on 25 November 2008 the Committee recommended that there should be no change to the current classification of lansoprazole 15 mg capsules as prescription medicine. The Committee was largely satisfied with the present submission, but agreed that appropriate warnings should be included on the pack and that further clarification was required regarding the efficacy of the proposed dose regimen.

At the 41^st meeting on 14 May 2009 the issue was not discussed as further information had not been submitted.

The submission was reconsidered now that the sponsor company had provided additional information in support of the classification change from prescription medicine to restricted medicine. The packaging had been revised to include "alarm signal" warnings. Nine references from the literature were provided displaying the efficacy of the proposed dosage of 15 mg daily.

One pre-meeting comment had been received during the consultation period and this was in support of the reclassification of lansoprazole 15 mg capsules from prescription medicine to restricted medicine.

The Committee noted that the labelling and safety requirements appeared to have been resolved, and that the data provided was supportive. The data was derived from evidence of effect at 24 hours on intragastric pH, and on interim analysis of four and eight week studies following 14 days treatment, and so seemed to demonstrate clear efficacy in terms of symptom resolution. Although the Committee felt that their requests of the sponsor company had not been fully met, there was no evidence to suggest that the risk benefit profile of lansoprazole 15 mg capsules would be significantly different from that seen for pantoprazole and omeprazole which have been reclassified.

The Committee concluded that lansoprazole should be reclassified from prescription medicine to restricted medicine provided that similar requirements were met to those detailed for the over-the-counter sale of both omeprazole and pantoprazole in the New Zealand Regulatory Guidelines for Medicines.

The requirements for lansoprazole as a restricted medicine:

1. it must be sold in the manufacturer's original pack
2. the strength in each dose unit should not exceed 15 mg
3. the maximum daily dose should not exceed 15 mg
4. the pack size must not exceed 14 dose units
5. the indication should be limited to the relief of heartburn and short-term, symptomatic relief of gastric reflux-like symptoms in sufferers aged 18 years and over
6. the following warning statements, or words of similar meaning, are required on the label:
   1. for short-term use only, except on medical advice
   2. do not use the medicine for any purpose other than that specified on the pack, except on medical advice
   3. do not use if you are experiencing weight loss, persistent regurgitation of food or vomiting, difficulty swallowing or symptoms of gastro-intestinal bleeding, except on medical advice
   4. consult a doctor if symptoms persist, recur or worsen or if new symptoms occur
   5. consult a doctor or pharmacist before use if you are pregnant or are taking any other medicines
7. the package insert should include all interactions specified on the data sheet.

Medsafe should insert these requirements into the appropriate section of the New Zealand Regulatory Guidelines for Medicines.

The Committee also recommended that the sponsor company should submit a product application because the product and new indication (i.e. relief of heartburn) needed to be approved by Medsafe.

Recommendation

That tablets or capsules containing 15 mg or less of lansoprazole should be reclassified as a restricted medicine when sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine.

That the requirements for lansoprazole to be classified as a restricted medicine should be inserted into the New Zealand Regulatory Guidelines for Medicines by Medsafe.

That the sponsor company should submit a product application, including relevant clinical data, for evaluation by Medsafe.

5.6

PDE-5 Inhibitors

At the 41^st meeting on 14 May 2009 the Committee agreed, in principle, with a proposal to classify phosphodiesterase type 5 (PDE-5) inhibitors as prescription medicines. This was intended to cover substances (including the analogues of sildenafil, vardenafil and tadalafil) with clinically significant PDE-5 inhibitory activity. The Committee requested that Medsafe identify appropriate wording for the Schedule entry to ensure that caffeine and other substances with very weak, clinically insignificant activity at the PDE-5 receptor were not inadvertently covered.

The Committee considered the following wording proposed by Medsafe; PDE-5 inhibitors should be classified as prescription medicines except:

• when specified elsewhere in the Schedule, or
• when present as an unmodified, naturally occurring substance.

Adoption of this approach would ensure that, unless specified elsewhere in the Schedule, all synthetic substances with PDE-5 inhibitory activity would be classified as prescription medicines. This covered products containing synthetic substances only and "natural" healthcare products that testing revealed had been spiked / adulterated with a synthetic PDE-5 inhibitor. Unmodified naturally occurring substances with PDE-5 activity, such as caffeine, pomegranate and extracts of Epimedium species, would be exempt from scheduling. Inclusion of the term "unmodified" was intended to reinforce the concept that the structure of a naturally occurring substance should not be altered. Therefore, a natural substance that had been chemically modified will be classified as a prescription medicine.

One member queried the use of the word unmodified. If a substance was highly concentrated it would not necessarily be considered as modified and so could be exempt from scheduling.

An interested body had submitted their own proposed wording to Medsafe which was in general agreement with the wording proposed above; the exception being that nature identical substances were specifically excluded from scheduling. However the term "nature identical" is not recognised by the Medicines Act 1981. Additionally, while a nature identical substance may bear the same chemical formula as the naturally occurring substance, it may not possess the same chirality or the same proportion of each optical isomer. This would affect the three-dimensional shape of the substance and may affect both pharmacological activity and the risk benefit profile of the product.

The Committee agreed with the proposed wording from Medsafe, that PDE-5 inhibitors should be classified as prescription medicines except when specified elsewhere in the Schedule, or when present as an unmodified, naturally occurring substance.

Recommendation

That PDE-5 inhibitors should be classified as prescription medicines except when:

• specified elsewhere in the Schedule
• present as an unmodified, naturally occurring substance.

5.7

Zolmitriptan
(Zomig nasal spray, AstraZeneca)

At the 41^st meeting the Committee recommended that:

1. a single prefilled nasal spray device containing not more than 5 mg of zolmitriptan should be reclassified from prescription medicine to restricted medicine when sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine
2. controls around the sale of a single prefilled nasal spray device containing not more than 5 mg zolmitriptan should be the same as those already in place for sumatriptan; these controls include the:
   1. indication should be limited to the acute relief of migraine attacks, with or without aura, in patients who have a stable, well-established pattern of symptoms
   2. inclusion of suitable contraindications on the label, particularly regarding possible cross allergy to sulfonamides
   3. inclusion of other warnings on the label, including use of the product with irregular heartbeat and use with other migraine medications
   4. Migraine Treatment Questionnaire is used by the pharmacist at each consultation unless it has previously been completed in the same pharmacy in the previous 12 months
3. Medsafe should be satisfied with the proposed warning labels of any zolmitriptan product seeking consent to be sold as an over-the-counter medicine.

Since the 41^st meeting the sponsor company had advised Medsafe that the single pack of Zomig nasal spray 5 mg was no longer available, the smallest pack size now being two devices per pack. The sponsor company had sought advice from their head office regarding the possibility of repackaging the two device pack into singles, however this was not permitted.

The Committee considered the reclassification of zolmitriptan from prescription medicine to restricted medicine when sold in packs of two devices. A number of points were raised by the Committee. There had not been an additional submission from the sponsor company displaying the packaging of a two device pack. It was noted there was no experience for New Zealand migraine sufferers with this medicine as it had not been on the market here, and usually nasal sprays were used with one spray in each nostril. However, pharmacists would be able to advise clearly the single dose only and that there are two separate devices in the pack. The packaging should include warnings about use during pregnancy; one nasal spray equates to one dose; the dose should not be repeated within 24 hours, and advertising should be in line with the dosing instructions. Medsafe should insert these requirements into the appropriate section of the New Zealand Regulatory Guidelines for Medicines.

The Committee concluded that they had no objection to the reclassification of zolmitriptan from prescription medicine to restricted medicine when sold in packs of two devices under the conditions discussed.

Recommendation

That a prefilled nasal spray device containing not more than 5 mg of zolmitriptan should be reclassified from prescription medicine to restricted medicine when sold in packs of not more than two devices which have been approved by the Minister or the Director-General for distribution as a restricted medicine.

That the controls around the sale of a prefilled nasal spray device containing not more than 5 mg zolmitriptan when sold in packs of not more than two devices should be the same as those already in place for sumatriptan.

That the requirements for zolmitriptan to be reclassified as a restricted medicine should be inserted into the New Zealand Regulatory Guidelines for Medicines by Medsafe.

That Medsafe should be satisfied with the proposed warning labels of any zolmitriptan product seeking consent to be sold as an over-the-counter medicine.

5.8

Fluoride

At the 40^th meeting on 25 November 2008 the Committee recommended that New Zealand should harmonise with Australia on the classification of fluoride products.

It had been brought to Medsafe's attention that the wording of the New Zealand Schedule did not harmonise exactly with that of the Australian Standard for the Uniform Scheduling of Drugs and Poisons (SUSDP). The prescription entry in the New Zealand Schedule read:

for internal use in medicines containing more than 0.5 mg per dose unit except in medicines containing 15 mg or less per litre or per kilogram; except in parenteral nutrition replacement preparations; for external use in medicines containing more than 5500 mg per litre or per kilogram except when used in practice by a registered dental therapist.

This current wording in the New Zealand Schedule requires products to be labelled as prescription medicines, then includes an exemption to allow supply without prescription to dental therapists. However, a product would still be required to state "prescription medicine" on the label rather than follow general sales labelling requirements. The SUSDP exempts products supplied to registered dental professionals from the prescription medicine entry and then allows states and territories to determine who else may have access to high concentration products. Companies do not want to have to label their products as prescription medicines and they argue only registered dental therapists are supplied anyway.

It had been suggested that the prescription entry should be amended to bring it in line with the wording in the SUSDP as follows:

for internal use in medicines containing more than 0.5 mg per dose unit except in medicines containing 15 mg or less per litre or per kilogram; except in parenteral nutrition replacement preparations; for external use in medicines containing more than 5500 mg per litre or per kilogram except when supplied to a registered dental professional or by approval of an appropriate authority.

The Committee considered the rewording of the exception. In New Zealand Medsafe is the appropriate authority so the rewording of "by approval of an appropriate authority" would not be appropriate. In its opinion, removal of the requirement for products to be exempt from scheduling would potentially expose the public to risk as high concentration fluoride products could be purchased over the internet or diverted to consumer use when imported.

The Committee concluded that it would not be appropriate to harmonise with Australia on the wording of the classification of the prescription entry of fluoride. Rather if interested bodies wished to supply to dental professionals without a prescription medicine label then they could discuss the possibility of a labelling exemption on a case-by-case basis with Medsafe.

Recommendation

That there should be no change to the wording of the prescription medicine entry for fluoride in the New Zealand Schedule.

5.9

Chloramphenicol for eye use

At the 40^th meeting on 25 November 2008 the Committee recommended that chloramphenicol for ophthalmic use should remain classified as a prescription medicine except when sold in practice by a registered optometrist. The Committee indicated their willingness to reconsider the request for reclassification from prescription medicine to restricted medicine if additional supporting information was provided.

The Pharmaceutical Society supplied this supporting material, including information on training for pharmacists and a treatment algorithm developed by the Royal Pharmaceutical Society of Great Britain proposed to be used in New Zealand. At the 41^st meeting on 14 May 2009 the Committee recommended that chloramphenicol for ophthalmic use should be reclassified from prescription medicine (except when sold in practice by a registered optometrist) to restricted medicine (except when sold in practice by a registered optometrist). The Committee also recommended that this recommendation be delayed until training had been provided to pharmacists and appropriate written information on the self-management of eye conditions was able to be given to all patients purchasing the medicine.

One member suggested Medsafe should write to the Pharmaceutical Society acknowledging their efforts made to date, and to request clarification that the training provided and written material on the self-management of eye conditions would be available for all pharmacists. Also, that it be made clear the medicine could only be supplied as a restricted medicine if the appropriate written information accompanied the supply.

Recommendation

That Medsafe should write to the Pharmaceutical Society acknowledging their efforts made to date and to request clarification that the training provided and written material on the self-management of eye conditions would be available for all pharmacists. Once assurance that all pharmacists would receive training material had been confirmed, the reclassification to restricted medicine would be gazetted.

6

SUBMISSIONS FOR RECLASSIFICATION

6.1

Omeprazole 20 mg tablet
(Losec MUPS tablets, Bayer New Zealand Ltd)

This was a company submission for the reclassification of omeprazole 20 mg tablets from prescription medicine to restricted medicine for the short term relief of reflux-like symptoms.

At the 38^th meeting on 14 December 2007 the Committee recommended that there should be no change to the current prescription medicine classification of omeprazole.

At the 40^th meeting on 25 November 2008 additional information had been supplied so the Committee recommended that tablets or capsules containing 10 mg or less of omeprazole should be reclassified from prescription medicine to restricted medicine when sold in packs which have received the consent of the Minister or the Director-General to their sale as restricted medicines and are sold in the manufacturer's original pack.

The present submission proposed extension of the recommendation to 20 mg tablets.

One pre-meeting comment had been received during the consultation period and this was in support of the reclassification. It was commented that the current restriction of 10 mg or less per dosage unit, but with a dosage recommendation of two tablets or capsules initially each day until symptoms improve, then reduce to one daily, with a maximum pack size of 14 dosage units was unnecessarily complicated for the patient. This could lead to confusion and non-compliance with the instructed regime. A single daily dose of one 20 mg tablet (the current maximum restricted dose) for the full 14 day course would solve this problem - and be more efficacious. There was no awareness of an increase in adverse effects from using 20 mg daily for such a short period.

The Committee discussed the possibility of patients using the tablets when not appropriate and that the packaging did not state to stop taking them once symptoms had resolved. However, within the submission there was evidence of benefit associated with continued use for 14 days and other markets had approved the dose regimen proposed for the product. The Committee concluded that omeprazole 20 mg tablets should be reclassified from prescription medicine to restricted medicine for the short term relief of reflux-like symptoms. Also that the label on the packaging should include the following statement, or words of similar meaning, "do not take for more than 14 days; if symptoms persist, talk to your Doctor".

Medsafe should insert these requirements into the appropriate section of the New Zealand Regulatory Guidelines for Medicines.

Recommendation

That tablets containing 20 mg of omeprazole or less should be classified as a restricted medicine when sold in packs approved by the Minister or the Director-General for distribution as a restricted medicine.

That the requirements for omeprazole to be classified as a restricted medicine should be inserted into the New Zealand Regulatory Guidelines for Medicines by Medsafe.

That Medsafe should be satisfied with the proposed warning labels of any product containing omeprazole seeking consent for distribution as a restricted medicine.

6.2

Fexofenadine hydrochloride 60 mg capsule, 120 mg film coated tablet and 60 mg film coated tablet
(Telfast, Sanofi-Aventis Australia Pty Ltd)

This was a company submission for the reclassification of fexofenadine hydrochloride 60 mg capsules, 120 mg film coated tablets and 60 mg film coated tablets from pharmacy-only medicine to general sales medicine for the treatment of Seasonal Allergic Rhinitis. Specifically the application sought to facilitate the supply of a small (maximum 10 dosage units) oral presentation of fexofenadine, when used only for short term treatment (maximum five days of therapy) in adults and children 12 years and over with a maximum daily dose of 120 mg.

At their 56^th meeting in June 2009, the NDPSC considered the scheduling of fexofenadine, including a proposal to exempt fexofenadine in preparations for oral use for the short term treatment of Seasonal Allergic Rhinitis. The NDPSC agreed to defer consideration until their October 2009 meeting so that data presented after the application could be evaluated.

Two pre-meeting comments had been received during the consultation period. One interested body supported the reclassification because it understood a significant number of New Zealanders were not adequately addressing their allergy problems. The other interested body did not support the reclassification. Despite an indication for Seasonal Allergic Rhinitis, it was suggested the public would see it as an antihistamine available from the supermarket for all sorts of other conditions. No questions would be asked by, or answers given by, supermarket checkout operators.

The main issue that the Committee's discussions surrounded were whether a patient could self diagnose Seasonal Allergic Rhinitis and whether it would be appropriate to have such a product for sale in the supermarket. Concerns were raised around pregnancy and whether patients would use the product for other indications.

The Committee concluded that these issues could be addressed by appropriate labels and so fexofenadine hydrochloride 60 mg capsules, 120 mg film coated tablets and 60 mg film coated tablets should be reclassified from pharmacy-only medicine to general sales medicine for the treatment of Seasonal Allergic Rhinitis.

The Committee recommended that a warning statement should be included on the pack to the effect of "do not use with other anti-histamines; this product should not be used when pregnant or when breast feeding except when advised by your Doctor or Pharmacist". Medsafe should insert these requirements into the appropriate section of the New Zealand Regulatory Guidelines for Medicines.

Recommendation

That capsules containing 60 mg or less and tablets containing 120 mg or less of fexofenadine hydrochloride should be classified as general sales medicines when:

• used only for short term treatment (maximum five days of therapy) of Seasonal Allergic Rhinitis
• used in adults and children 12 years and over
• used in small (maximum 10 dosage units) oral presentations with a maximum daily dose of 120 mg
• sold in packs approved by the Minister or the Director-General for distribution as a general sales medicine.

That the requirements for fexofenadine hydrochloride to be classified as a general sales medicine should be inserted into the New Zealand Regulatory Guidelines for Medicines by Medsafe.

That Medsafe should be satisfied with the proposed warning labels of any product containing fexofenadine hydrochloride seeking consent for distribution as a general sale medicine.

6.3

Diclofenac 12.5 mg film coated tablet
(Voltaren Rapid, Novartis Consumer Health Australasia Pty Ltd)

This was a company submission to increase the maximum pack size for pharmacy-only sale of diclofenac 12.5 mg film coated tablets from 20 to 40 dosage units. No changes to the product dose or strength were being sought. The indications are for the temporary relief of painful conditions, the temporary relief of symptoms of cold and flu, and the reduction of fever.

At the 38^th meeting on 14 December 2007 the Committee considered a submission for an increase in the permitted pack size for pharmacy-only sale of 12.5 mg tablets or capsules from 20 dose units to 40 dose units per pack. The Committee recommended there should be no change to the pack size limit of 20 dose units for 12.5 mg diclofenac tablets or capsules when sold as pharmacy-only medicines. An increase in pack size did not meet the criterion for short-term use for over-the-counter medicines. Larger pack sizes could lead to longer term use which could lead to more adverse effects. In the present submission new data had been provided to support the proposed reclassification.

One pre-meeting comment had been received during the consultation period and this was not in support of the reclassification. It was commented that doubling the pack size was equivalent to doubling the dose.

The Committee felt that although the sponsor company presented a strong case for packs of 40 dosage units in terms of safety and significant risk, they would be more comfortable with 5 days supply, i.e. 30 dosage units. This product was approved only for temporary relief of self limited conditions and that the maximum pack size the Committee would support was 5 days supply.

Recommendation

That there be no change to the current classification of diclofenac as pharmacy-only medicine when in solid dose form in medicines containing 12.5 mg or less per dose form, in packs containing not more than 20 tablets or capsules and with a recommended daily dose of not more than 75 mg.

That a company submission to increase the maximum pack size for pharmacy-only sale of diclofenac 12.5 mg film coated tablets from 20 to 30 dosage units would be considered if submitted.

7

NEW MEDICINES FOR CLASSIFICATION

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

7.1

Corifollitropin alfa
(Elonva solution for injection, 100 μg/0.5 mL and 150 μg/0.5 mL)

Corifollitropin alfa is classified as a Sustained Follicle Stimulant, a gonadotropin with different pharmacokinetic properties, but similar pharmacological features as Follicle Stimulating Hormone. Corifollitropin alfa is a glycoprotein dissolved in a colourless, clear solution.

Corifollitropin alfa is a gonadotropic hormone indicated for the treatment in Controlled Ovarian Stimulation to induce the development of multiple follicles and pregnancy in women participating in an Assisted Reproductive Technology programme.

Recommendation

That corifollitropin alfa should be classified as a prescription medicine.

7.2

Pazopanib hydrochloride
(Patorma film coated tablet, 200 mg and 400 mg)

Pazopanib hydrochloride is an orally administered, tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, platelet-derived growth factor (PDGFR)-α and -β, and stem cell factor receptor (c-KIT).

Pazopanib hydrochloride is indicated for the treatment of advanced and / or metastatic renal cell carcinoma.

Recommendation

That pazopanib hydrochloride should be classified as a prescription medicine.

7.3

Ginkgo biloba

Ginkgo biloba was presented to the Committee for information only. Medsafe had received a New Medicine Application for a medicine containing an extract from Ginkgo biloba.

Neither Ginkgo biloba nor its extract, referenced by the manufacturer as EGb 761, had previously been used in a medicine for which the sponsor had received approval to distribute. Consequently, the medicine is "an innovative new medicine" according to Medsafe policy.

EGb 761 contains various active principles and components, among which are chiefly gingkolides, bilobalides, and terpene lactones. This extract is of high quality, and is the reference standard for Germany's Commission E monograph. Other Ginkgo biloba extracts are measured against this standard.

The Committee noted that this formed the first instance of an application being made for approval under section 20 of the Medicines Act 1981, for a medicine containing a herbal extract. Concern was expressed that any decision to classify ginkgo biloba would not only affect this product but all products containing ginkgo biloba. The Committee felt they would be able to make a more informed decision if they were provided with further data relating to the classification of ginkgo biloba.

Recommendation

That the classification of ginkgo biloba be deferred until the next meeting so that the Committee can consider the data relating to the classification.

That Medsafe supply the Committee with further information on the safety and toxicity of the product.

8

HARMONISATION OF NEW ZEALAND AND AUSTRALIAN SCHEDULES

8.1

New chemical entities which are not yet classified in New Zealand

8.1.1

Japanese Encephalitis Vaccine

Japanese encephalitis vaccine is used for active immunisation against encephalitis.

Recommendation

That Japanese encephalitis vaccine should be added to the New Zealand Schedule as a prescription medicine.

8.1.2

Human Papillomavirus Vaccine

Human papillomavirus vaccine is a non-infectious, subunit viral vaccine for use in immunisation against infection caused by human papillomavirus.

Recommendation

That human papillomavirus vaccine should be added to the New Zealand Schedule as a prescription medicine.

8.2

Recommendations made by the National Drugs and Poisons Schedule Committee (NDPSC) to the MCC

8.2.1

55^th Meeting on 17-18 February 2009

There were no unresolved recommendations.

8.2.2

56^th Meeting on 16-17 June 2009

The NDPSC considered scheduling 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (more commonly known as 'statins') as a class entry. They reduce cholesterol by stimulating an increase in low-density-lipoprotein-receptors (LDL) on hepatocyte membranes, thereby increasing the clearance of LDL from the circulation.

Within their discussions, the NDPSC considered a submission to assess the suitability of red yeast rice extract, which contains lovastatin, as a restricted medicine. However, the NDPSC agreed to include an entry for all HMG-CoA reductase inhibitors in Schedule 4 (prescription medicine) of the SUSDP.

The Committee considered harmonising with the above classification and whether there should be a general prescription medicine entry for HMG-CoA Reductase inhibitors in the Schedule. The class entry for HMG-CoA reductase inhibitors would, like the phosphodiesterase type 5 (PDE-5) inhibitors class entry, capture all HMG-CoA reductase inhibitors that are yet to be considered for scheduling. The main issue the Committee considered was that foodstuffs and dietary supplements would be included if a general entry was included in the Schedule. However, it was noted by the Committee that the NDPSC were not necessarily required to differentiate dietary supplements from medicines, as was the case in New Zealand.

Two pre-meeting comments had been received during the consultation period. One commented that foodstuffs, such as red yeast rice and oyster mushrooms, should be excluded from the classification. The other commented that they did not support class entries in the Schedule; when a medicine is registered its classification should be listed under the generic name.

A similar approach to that of the PDE-5 inhibitors class entry was suggested, where HMG-CoA reductase inhibitors could be classified as prescription medicines except when specified elsewhere in the Schedule, or when present as an unmodified, naturally occurring substance. The Committee felt they would benefit from further information regarding the indications and side effect profile of lovastatin specifically before making a decision on harmonisation. Two methods were suggested:

1. To approach a distributor of red yeast rice extract and request safety information about that product in light of the recommendations from the NDPSC.
2. To request that Medsafe provide a literature review of lovastatin.

Recommendation

To delay making a recommendation on the classification of HMG-CoA reductase inhibitors until further information on the indications and side effect profile of red yeast rice extract, which contains lovastatin, and a literature review of lovastatin, can be considered.

The NDPSC decided to amend the entry for loperamide in the SUSDP to clarify that liquid preparations of loperamide were classified as prescription medicines. Loperamide is currently indicated for the symptomatic treatment of acute diarrhoea, the treatment of chronic diarrhoea, antipropulsive control and the reduction of discharge in patients with intestinal resection.

Medsafe proposed to clarify the classification status of loperamide liquid preparations in New Zealand by amending the wording for the prescription medicine Schedule entry to read "except when specified elsewhere in this Schedule". The condition currently reads "in packs containing more than 20 tablets or capsules".

Loperamide would remain pharmacy-only when in packs containing not more than 20 tablets or capsules.

The Committee noted that there were no liquid preparations to date in New Zealand and that no applications had been received. The Committee agreed to amend the wording of the prescription medicine New Zealand Schedule entry.

Recommendation

That New Zealand should harmonise with Australia by amending the prescription medicine entry for loperamide so that the condition reads "except when specified elsewhere in this Schedule".

9

FOR THE NEXT MEETING

A number of items for the present meeting were suggested at the 41^st meeting on 14 May 2009, however whether or not these would be considered depended on whether submissions for reclassification were received from sponsor companies or other interested bodies. One member noted it was interesting that no submissions had been received following the suggestions made.

Items from this meeting that may be considered at the next meeting were:

• diclofenac 12.5 mg film coated tablet (agenda item 6.3)
• gingko biloba (agenda item 7.3)
• HMG-COA reductase inhibitors ('statins') (agenda item 8.2.2a).

10

GENERAL BUSINESS

10.1

Ibogaine and its metabolite noribogaine

Medsafe had received several enquiries about importing ibogaine into New Zealand. In response to these requests, Medsafe decided to clarify the scheduling status.

The Committee was therefore asked to consider the scheduling of ibogaine.

Ibogaine is a naturally occurring indole alkaloid derived from the roots of the rain forest shrub Tabernanthe iboga. It is used in low doses by the indigenous peoples of western Africa to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. The use of ibogaine for the treatment of drug dependence had been based on anecdotal reports from American and European addict self-help groups that it decreased the signs of opiate withdrawal and reduced drug craving for cocaine and heroin for extended time periods. Although ibogaine has diverse effects on the central nervous system (CNS), the pharmacological targets underlying the physiological and psychological actions of ibogaine are not completely understood.

The purported efficacy of ibogaine following single-dose administrations may be due to the formation of an active metabolite. Ibogaine is O-demethylated to 12-hydroxyibogamine (noribogaine) by the activity of liver enzymes. Noribogaine appears to have a slow clearance rate in humans, suggesting that some of the after effects of ibogaine may be due to the actions of the metabolite.

The Committee was provided with a table of data which attempted to state what is known regarding ibogaine related fatalities in the public domain. The figures suggest that the number of deaths due to methadone, the most controlled substance, were a little higher that those associated with ibogaine, which is unregulated.

The most frequently reported use for ibogaine is for the reduction or elimination of addiction to opiates. Ibogaine is reported to alleviate the symptoms of opiate withdrawal. It has also been suggested that ibogaine may be useful in treating dependence to other substances such as alcohol, methamphetamine and nicotine.

Given its use for the therapeutic purpose of managing/treating addiction and the need for this treatment to be under supervision, Medsafe believed that there was a case for classifying ibogaine and its metabolite noribogaine as prescription medicines. This would not necessarily restrict the medical use in a therapeutic environment but would limit attempts at self treatment and prevent its development for recreational use as a "party pill", even though the documented experience of using it is usually not that pleasant.

Medsafe had also sought opinion from a psychiatrist who is proposing to conduct a clinical study utilising ibogaine. He was of the opinion that although its appeal as a recreational drug is low, he shared concerns that use in an ad hoc fashion as a self medication for drug addiction could occur following the media interest in the product and that this could be dangerous. The psychiatrist was supportive of classification of ibogaine as a prescription medicine.

Due to the potential for therapeutic use of the product, the safety profile and the potential for misuse, Medsafe suggested that the substance ibogaine and its metabolite noribogaine met the criteria for classification under the Medicines Act 1981. This would provide ability to control the import and supply of ibogaine, its metabolite or any products containing each or both of the substances.

The Committee agreed with the recommendation to classify ibogaine as a prescription medicine.

Recommendation

That ibogaine and its metabolite noribogaine should be classified as prescription medicines.

10.2

Committee members

The Chair thanked Ms Gauld for her commitment and contribution to the Committee over the past two terms.

The Chair similarly thanked Dr Peckham. Even though a replacement from the Medical Association of New Zealand had yet to be nominated, if one was appointed before the next meeting then this would be Dr Peckham's last.

11

DATE OF NEXT MEETING

To take place in April 2010, ideally on a Tuesday.