National Drugs and Poisons Schedule Committee

Record of Reasons

43rd Meeting 22-23 February 2005

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 i

TABLE OF CONTENTS

GLOSSARY...... III 1.7.1.5 Appendix A - Blood Products ...... 1 1.7.1.8 Gazettal of ‘No Change’ Scheduling Recommendations ...... 3 1.8 NDPSC WORKING PARTIES ...... 6 1.8.1 Trans-Tasman Harmonisation Working Party ...... 6 1.8.1.2.2 Aciclovir ...... 6 1.8.1.2.3 Hyoscine Butylbromide ...... 8 1.8.1.2.4 Juniperus Sabine/Savin Oil...... 11 1.8.1.2.5 Nicotine in NRT ...... 13 1.8.1.2.6 Alclometasone and Clobetasone ...... 16 1.8.1.2.7 Hyoscine and Hyoscyamine...... 19 1.8.1.2.8 Paracetamol 665 mg...... 21 1.8.1.2.9 Ibuprofen ...... 22 1.8.1.3.1 Strychnos spp...... 24 1.8.1.4 Outcomes from TTHWP 13th Meeting...... 26 2. PROPOSED CHANGES/ADDITIONS TO PARTS 1 TO 3 AND PART 5 OF THE STANDARD FOR THE UNIFORM SCHEDULING OF DRUGS AND POISONS...... 33 2.2 SUSDP, PART 2...... 33 2.2.1 Labels for Schedule 8 Substances...... 33 2.2.2 Containers for Essential Oils...... 35 AGRICULTURAL/VETERINARY, INDUSTRIAL AND DOMESTIC CHEMICALS...... 37

4. OTHER OUTSTANDING MATTERS FROM PREVIOUS MEETINGS...... 37 4.1 EYELASH AND EYEBROW TINTING PRODUCTS ...... 37 4.2 PYRAFLUFEN ETHYL ...... 44 4.3 SODIUM HYDROXIDE...... 46 4.4 PINE OILS ...... 48 6. MATTERS REFERRED BY THE AUSTRALIAN PESTICIDES AND VETERINARY MEDICINES AUTHORITY...... 51 6.1 ALPHA-AMYLASE / BETA-GLUCONASE / CELLULASE / PECTINASE / PHYTASE / FUNGAL PROTEASE / XYLANASE...... 51 6.2 FIPRONIL AND 4-[4(ACETYLOXY)PHENYL]-2-BUTANONE (CUE LURE) ...... 51 6.3 POTASSIUM PEROXOMONOSULFATE/SILVER/ COPPER/SODIUM PERSULFATE ...... 52 6.4 THIABENDAZOLE...... 52 6.5 DERACOXIB...... 53 6.6 FORCHLORFENURON ...... 53 7. MATTERS REFERRED BY OFFICE OF CHEMICAL SAFETY (OCS) BRANCH...... 53 7.1 GLYCOLIC ACID...... 53 9. OTHER MATTERS FOR CONSIDERATION ...... 55 9.1 CARBAMIDE PEROXIDE...... 55 12. MATTERS ARISING FROM THE MINUTES OF THE PREVIOUS MEETING (CONSIDERATION OF POST-MEETING SUBMISSIONS UNDER 42ZCZ)...... 60 12.1 ASPIRIN...... 60

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 ii

12.2 KETAMINE...... 65 13. OTHER OUTSTANDING MATTERS FROM PREVIOUS MEETINGS ...... 68 13.1 PSEUDOEPHEDRINE ...... 68 13.2 ARIPIPRAZOLE...... 73 13.3 MELIA AZEDARACH ...... 76 13.4 ROSUVASTATIN ...... 79 13.6 ZINC COMPOUNDS...... 81 13.7 2,5-DIMETHOXY-4-ETHYLTHIOPHENETHYLAMINE (2C-T-2) / 2,5-DIMETHOXY-4- IODOPHENETHYLAMINE (2C-I) / 2,5-DIMETHOXY-4-(N)-PROPYLTHIOPHENETHYLAMINE (2C-T-7) / 5-METHOXY-A-METHYLTRYPTAMINE (5-MEO-AMT) ...... 85 13.8 IBUPROFEN...... 87 14. PROPOSED CHANGES/ADDITIONS TO THE STANDARD FOR THE UNIFORM SCHEDULING OF DRUGS AND POISONS...... 94 14.1 SUSDP, PART 4 ...... 94 14.1.1 Oseltamivir...... 94 14.1.2 Diphenhydramine...... 99 14.1.3 Diclofenac...... 102 14.2 SUSDP, PART 5 ...... 109 14.2.1 Appendix H ...... 109 14.2.1.1 Orlistat ...... 109 14.2.2 REQUIRED ADVISORY STATEMENTS FOR MEDICINE LABELS ...... 113 15. MATTERS REFERRED BY THE AUSTRALIAN DRUG EVALUATION COMMITTEE (ADEC) 138 15.1 NEW SUBSTANCES ...... 138 15.1.1 Moxonidine ...... 138 15.1.2 Efalizumab ...... 138 15.1.4 Emtricitabine ...... 139 23. AMENDMENTS TO THE SUSDP...... 139 23.1 EDITORIAL CHANGES AND ERRATA ...... 139 23.1.1 Hyoscyamus niger...... 139 23.1.2 Selenium...... 140 23.1.3 Aspirin – for information ...... 141

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 iii

GLOSSARY

ABBREVIATION NAME

AAN Australian Approved Name

AC Active Constituent

ACSPA Australian Consumer and Specialty Products Association

ADEC Australian Drug Evaluation Committee

ADI Acceptable Daily Intake

ADRAC Adverse Drug Reactions Advisory Committee

AGRD Australian Guidelines for the Registration of Drugs

AHMAC Australian Health Ministers' Advisory Council

APMF Australian Paint Manufacturers Federation

APVMA Australian Pesticides and Veterinary Medicines Authority

AQIS Australian Quarantine and Inspection Service

ARfD Acute Reference Dose

ASMI Australian Self-Medication Industry

ARTG Australian Register of Therapeutic Goods

BAN British Approved Name

CAS Chemical Abstract Service

CHC Complementary Healthcare Council of Australia

CMEC Complementary Medicine Evaluation Committee

CMI Consumer Medicine Information

COAG Councils Of Australian Governments

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 iv

CPAS Chemical Product Assessment Section

CRC Child-Resistant Closure

CRIH Chemical Review and International Harmonisation

CTFAA Cosmetic, Toiletry & Fragrance Association of Australia

DAP Drafting Advisory Panel

DSEB Drug Safety and Evaluation Branch

EAGAR Expert Advisory Group on Antimicrobial Resistance

ECRP Existing Chemicals Review Program

EPA Environment Protection Authority

ERMA Environmental Risk Management Authority

FAISD First Aid Instructions and Safety Directions

FDA Food and Drug Administration (US)

FOI Freedom of Information

FSANZ Food Standards Australia New Zealand

GHS Globally Harmonised System for Classification and Labelling of Chemicals.

GIT Gastro-intestinal tract

GP General Practitioner

HCN Health Communication Network

INN International Non-proprietary Name

ISO International Standards Organization

JETACAR Joint Expert Advisory Committee on Antibiotic Resistance

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 v

LC50 The concentration of a substance that produces death in 50% of a population of experimental organisms. Usually expressed as mg per litre (mg/L) as a concentration in air.

LD50 The concentration of a substance that produces death in 50% of a population of experimental organisms. Usually expressed as milligrams per kilogram (mg/kg) of body weight

MCC Medicines Classification Committee

MEC Medicines Evaluation Committee

MOH Ministry of Health (NZ)

NCCTG National Coordinating Committee of Therapeutic Goods

NDPSC National Drugs and Poisons Schedule Committee

NHMRC National Health and Medical Research Council

NICNAS National Industrial Chemicals Notification & Assessment Scheme

NOEL No Observable Effect Level

NOHSC National Occupational Health & Safety Commission

NPMB Non-Prescription Medicines Branch

NZ New Zealand

OCM Office of Complementary Medicines

OCS Office of Chemical Safety

ODBT Office of Devices, Blood and Tissues

OOS Out of Session

OTC Over the Counter

PACIA Plastics And Chemicals Industries Association

PAR Prescription Animal Remedy

PBAC Pharmaceutical Benefits Advisory Committee

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 vi

PEC Priority Existing Chemical

PGA Pharmaceutical Guild of Australia

PHARM Pharmaceutical Health and Rational Use of Medicines

PI Product Information

PIC Poisons Information Centre

PSA Pharmaceutical Society of Australia

RFI Restricted Flow Insert

SUSDP Standard for the Uniform Scheduling of Drugs and Poisons

SVT First aid for the solvent prevails

TCM Traditional Chinese Medicine

TGA Therapeutic Goods Administration

TGC Therapeutic Goods Committee

TGO Therapeutic Goods Order

TTHWP Trans-Tasman Harmonisation Working Party

TTMRA Trans-Tasman Mutual Recognition Agreement

UK United Kingdom

USA United States of America

WHO World Health Organization

WP Working Party

WS Warning statement

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 1

1.7.1.5 APPENDIX A - BLOOD PRODUCTS

PURPOSE

The Committee considered the inclusion of an entry for blood products for therapeutic use in Appendix A of the SUSDP for the exemption of such products from the requirements of scheduling.

BACKGROUND

Historically, the Committee had a 'standing policy' of not scheduling blood products when used in the clinical or hospital settings. The Committee was of the view that scheduling such products would place unwarranted and potentially excessive restrictions via the SUSDP when the supply and safe use of such products could be adequately controlled through Commonwealth and State/Territory mechanisms.

The May 2001 NDPSC meeting considered the scheduling of a recombinant Factor VIII product, octocog alfa, where the Committee agreed that its safety profile was consistent with similar blood products already exempt from scheduling. At this meeting, the Committee also considered a proposal to include a general exemption for blood products for therapeutic use in Appendix A of the SUSDP to reflect the Committee's policy of not scheduling blood products for supply or use in the clinical or hospital settings. The Committee then agreed to consider the proposal in detail when the recommendations arising from the Review of the Australian Blood Banking and Plasma Product Sector (the Review) became available. Furthermore, the Committee noted that recombinant Factor VIII was classified as Pharmacy-Only medicine in New Zealand.

The final report of the Review was subsequently released in 2001 and was made available to the NDPSC for inclusion on the agenda of the February 2005 meeting for information of members and to facilitate the consideration of the need to schedule blood products for therapeutic use.

DISCUSSION

The Committee noted the Review of the Australian Blood Banking and Plasma Product Sector was a comprehensive examination of Australia’s blood banking and plasma product sector to ensure that Australia is equipped nationally to meet emerging and future challenges, to provide an adequate and secure supply of safe, high quality blood and blood products and to promote appropriate clinical use. Members noted that, although the Review did not specifically suggest any scheduling procedures for blood products, it was recommended that the Commonwealth Government provide funding for the establishment and operation of a National Blood Authority (NBA), a statutory body under Commonwealth legislation that provides national management and oversight of the Australian blood supply and to develop and implement contingency planning to manage supply risks. Members also noted that the recommendation from the Review that effective lines of communication and advice should be established between the NBA in

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 2

managing and planning Australia’s blood supply and the TGA in regulating blood, blood components and plasma derivatives under the Therapeutic Goods Act 1989 to ensure a national approach in setting standards, including regulatory standards, in the context of public health policy and risk management.

The NBA was established on 1 July 2003 under the National Blood Authority Act 2003 with the following specific roles:

• coordinate national demand and supply planning of blood and blood products and purchase those products on behalf of all Australian governments; • negotiate and manage contracts on behalf of all States and Territories and the Australian government with suppliers of blood and blood products to enable the development of an agreed single national pricing schedule; • implement an efficient demand-driven system, based upon evidence and good clinical practice, so that the blood supply system is highly responsive to needs; and • work in a collaborative manner with all governments and other responsible parties to ensure that Australia's blood supply is safe, secure, adequate and affordable. The establishment of the NBA has brought about a number of benefits to the blood sector including simplified purchasing arrangements between governments and suppliers resulting in increased accountability, strengthened negotiating positions with suppliers, more appropriate supply of blood and blood products to all States and Territories in line with jurisdictional demand and effective management of shortages of specific products to ensure sufficiency of supply.

The Committee noted that the National Blood Authority Act defined ‘blood products’ as those products that are used or intended for use for human therapeutic or diagnostic purposes that consist of human blood or are derived from human blood. Members also noted that under the Therapeutic Goods Act 1989, 'blood' was defined as whole blood extracted from human donors and that 'blood components' were therapeutic components that have been manufactured from blood (including red cells, white cells, progenitor cells, platelets and plasma). It was further noted that 'blood components' did not include products derived through fractionation of plasma.

The Committee intended that an Appendix A entry which exempted blood products would include such products containing substances considered to be of low abuse or misuse potential on the basis that such products were used exclusively within the hospital and clinical setting. Members proposed taking the same approach as that taken for medical devices and agreed that the Appendix A entry should specify the group of blood products that were not appropriate for exemption, for example those products containing substances with high potential for abuse and diversion such as erythropoietins. Members agreed that future amendments to the proposed Appendix A entry could be made on a case-by-case basis via the usual NDPSC procedures where appropriate.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 3

OUTCOME

The Committee was satisfied that there are regulatory mechanisms in place at State/Territory level and at a national level as administered by the NBA in managing and overseeing the national blood supply and the TGA in regulating the safety, efficacy and quality of blood and blood products to warrant the exclusion of blood products from the SUSDP.

Furthermore, the Committee agreed to foreshadow the inclusion in the SUSDP of an Appendix A entry to exempt blood products from the requirements of scheduling and that the proposed exclusions to this entry were for blood derived products containing substances appropriate for scheduling and those already included in the Schedules which the Committee wished to remain subject to scheduling requirements as appropriate. In addition, the Committee confirmed its view that future amendments to the proposed Appendix A entry would be considered on a case-by-case basis according to the normal procedures of the NDPSC.

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Appendix A – New entry

BLOOD PRODUCTS for use in clinical and hospital setting except when separately specified in the Schedules.

Part 1 – Interpretation – New Entry

Sub-paragraph 1.(1)

“Blood products” means products that are used or intended for use for human therapeutic or diagnostic purposes consisting of human blood including its components or derivatives.

1.7.1.8 GAZETTAL OF ‘NO CHANGE’ SCHEDULING RECOMMENDATIONS

PURPOSE

The Committee considered a proposal to allow applicant comment when the NDPSC decides to make no change to the scheduling of a substance.

BACKGROUND

XXXXXXXXX, at the October 2004 NDPSC meeting, flagged the matter of allowing sponsors who made a scheduling application to make a post-meeting comment where a decision is made to not change the SUSDP. The Committee noted that the current post- meeting public consultation procedure prescribed in the legislation did not allow for

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interested stakeholders to make further submissions where there was no amendment to the SUSDP.

Correspondence was subsequently received from XXXXXXXXX supporting this proposal.

The relevant pieces of legislation governing the Committee’s procedures for allowing comment on decisions are as follows.

• Subregulation 42ZCY(1) of the Therapeutic Goods Regulations 1990 (the Regs) requires a notice under subsection 52D(4) of the Therapeutic Goods Act 1989 (the Act) to include: (a) an indication of the amendment; and (b) instruction on how the record of the reasons for the amendment may be accessed; and (c) an invitation to persons who made a public submission in relation to the substance the subject of the amendment to make a further submission.

• Subsection 52D(4) of the Act requires that after an amendment is made to the current SUSDP, the Committee must cause a notice to be published in the Gazette stating: (a) that an amendment has been made to the Poisons Standard; and (b) the date on which the amendment comes into effect; and (c) a place from which copies of the amendment can be purchased.

Subsection 52D(5) of the Act defines amend, in relation to the current Poisons Standard, to mean to alter, omit or insert any provision. A ‘no scheduling change’ would not alter, insert or omit any provision of the SUSDP and as such subregulation 42ZCY(1) would not be applicable.

On the basis of subregulation 42ZCY(1), the Secretariat does not publish decisions to make 'no scheduling change' in the post-meeting Gazette notice. These decisions, however, are recorded in the record of reasons in accordance with regulation 42ZCX of the Regs.

DISCUSSION

The Committee considered XXXXXXXXX’s correspondence supporting a proposal to allow stakeholders to comment when the NDPSC decides to make no change to the scheduling of a substance. The Committee was advised by XXXXXXXXX that XXXXXXXXX’s request reflects industry’s concern that there is no opportunity for comment as a consequence of a ‘no scheduling change’ decision.

The Committee noted that the current public consultation process starts with a gazette notice being published inviting comment about a substance under consideration. The

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scheduling is then considered by the NDPSC. The subsequent process depends on the outcome of this consideration.

• Where a change to the schedule is agreed upon, those stakeholders who made a pre- meeting submission are allowed to make a further public submission on the outcome. These new submissions are then put to the Committee at the next meeting when they consider whether to confirm, amend or set aside their decision. This reconsideration requires no gazettal. • Where a ‘no scheduling change’ decision has been reached there is no requirement for further public consultation. If the applicant disagrees with this decision then they are free to submit a new application for a scheduling change. • The Committee noted that XXXXXXXXX’s proposal would limit post-meeting comment on a ‘no scheduling change’ to the sponsor who provided pre-meeting comment and would narrow the freedom for comment now practiced through foreshadowing. • The Committee agreed that XXXXXXXXX advice on two occassions found that a ‘no scheduling change’ decision completes the Committee’s obligation to undertake public consultation as prescribed in the legislation and that if someone is aggrieved by such a decision they could put in another submission. • The Committee was willing to receive post-meeting comment from sponsors on a ‘no scheduling change’ decision at the following meeting. In this case, where the comment justifies a scheduling change, this will be foreshadowed in the record of reasons. This foreshadowed change has the status of a new application requiring pre- meeting gazettal which allows other interested stakeholders to comment. • The Committee noted that the NDPSC’s processes are currently being reviewed by the NCCTG as part of the revised administrative arrangements for scheduling under the new trans-Tasman agency and there may be opportunity for change. OUTCOME

The Committee noted XXXXXXXXX’s correspondence and reconfirmed the following steps:

• Where a decision is made not to make a scheduling change, the legislation provisions do not require post-meeting gazettal and as such the public consultation process has been completed; and • Should an applicant want the matter to be reconsidered then it has the right to make a new scheduling application which would be subject to the usual public consultation procedures.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 6

1.8 NDPSC WORKING PARTIES

1.8.1 TRANS-TASMAN HARMONISATION WORKING PARTY

1.8.1.2.2 ACICLOVIR

PURPOSE

The Committee considered the harmonisation of scheduling for acyclovir in 5% preparations for the treatment of herpes labialis.

BACKGROUND

The November 2001 NDPSC Meeting considered an application from XXXXXXXXX to exempt XXXXXXXXX containing 5%w/w aciclovir from the requirements of scheduling when sold in a small pack size of 2g. The Committee agreed to exempt preparations containing 5 per cent or less of aciclovir for the treatment of Herpes labialis in packs containing 10g or less, on the grounds that Herpes labialis was a short term and self- limiting condition, appropriate for self-diagnosis and management by consumers. In addition, the product was simple to use and increased access to such a product would be beneficial to public health.

It was recommended to the New Zealand Ministry of Health that it adopt similar scheduling and New Zealand considered rescheduling of aciclovir at the May 2002 MCC Meeting.

However, MCC rejected NDPSC's recommendation on the grounds that MCC considered that the larger pack size did not fit the criterion of short-term use and increased the risk of inappropriate use. In particular, MCC considered that the availability of a larger pack-size suggested chronicity and the need for other intervention. MCC furthermore considered that larger pack sizes increased the risk that the product might be used in the genital area. On this basis, MCC agreed that tubes containing 3 grams or less should be reclassified to general sale but that tubes containing more than 3 grams should remain pharmacy-only medicines.

The issue was placed on the 2 year list with further consideration of harmonisation of scheduling being deferred until October 2004.

DISCUSSION

NDPSC noted that, in further considering harmonisation of the scheduling of aciclovir, the TTHWP had noted that:

• Prior to the NDPSC’s decision to exempt preparations containing 5 per cent or less of aciclovir for the treatment of Herpes labialis in packs containing 10 g or less, aciclovir in preparations containing 5% or less for dermal use had been included in

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 7

schedule 2 without limitation of pack size. 10 gram packs had been available as S2 medicines. • Inclusion of the 10g pack size restriction on exempt products containing 5% or less of aciclovir was considered appropriate by NDPSC to minimise the regulatory impact on products registered at that time. • The evaluation of the application for rescheduling noted the low potential for intentional misuse or abuse, the low incidence of adverse effects or side effects, the low risk of masking a serious disease or compromising the medical management of a disease. • At the time of consideration, therapeutic products including idoxuridine dermal preparations containing 0.5% idoxuridine for the treatment of cold sores, and other antiviral products had been available in supermarkets for a long time. • Appropriate labelling could address issues of concern in respect to inappropriate use • The data presented were considered by the reviewer and the NDPSC to be sufficient to meet the criteria used by the NDPSC (and the MCC) for the reclassification to an ‘exempted’ medicines classification. As the product was already available in larger pack size as an S2 medicine, the NDPSC’s consideration and the comments received from professional pharmacy bodies did not suggest that wider availability by way of a 10 g pack size exemption from scheduling would lead to inappropriate use including use in the genital area.

Aciclovir should be applied to the lesions or impending lesions as early as possible after the start of an infection. It was particularly important to start treatment of recurrent episodes during the prodromal period or when the lesions first appear. The availability of a 10 gram pack (with a shelf-life of 24 months) was therefore consistent with the need for recurrent use.

NDPSC noted that in New Zealand, topical preparations in pack sizes of 3 gram or less were available as a general sales medicine. Consequently, 3 gram packs (and multiple purchases) were freely available from non-pharmacy outlets. It was therefore not clear how this approach alleviated concerns of increased risk of inappropriate use or increased risk of use in the genital area. The Working Party considered that, in this respect, evidence of misuse in New Zealand would be useful.

In Australia, there had been only a few ADRAC reports of adverse reactions and no reports associated with inappropriate use of aciclovir. The incidence of adverse reports since the time when 5% aciclovir was exempted from scheduling in Australia had also not increased.

A search of the literature by TTHWP had not found any evidence of misuse of topical preparations containing aciclovir for the treatment of genital herpes. The UK Medicines and Healthcare Products Regulatory Agency noted, during the public consultation process associated with the reclassification of aciclovir from Pharmacy to a General Sales Listing

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in March/April 2004 that “the risk of misuse of XXXXXXXXX was considered small, and equally important, the risks associated with any such misuse was minimal. Patients should be able to self-diagnose and manage their disease, particularly with an indication such as cold sores. The Product Information Leaflet will permit patients to use the product correctly”. The maximum pack size for the GSL supply of aciclovir in the UK is 2 g. This was the pack size exemption sought by XXXXXXXXX.

The NDPSC noted that TTHWP had confirmed from ADEC Minutes that the original company submission was for 2, 5 and 10 gram tubes. The New Zealand representative on the TTHWP confirmed that MCC had considered 10 gram tubes to be excessive and increased the risk of the product being used for the treatment of genital herpes. However, it was also acknowledged that within both New Zealand and Australia, there was no evidence of misuse and therefore it would be appropriate for the New Zealand MCC to reconsider harmonisation on the 10 gram pack size.

The Working Party had therefore agreed to recommend to the NDPSC that harmonisation on the 10 gram pack size be reconsidered by the New Zealand MCC. In the meantime, the Working Party had written formally to XXXXXXXXX requesting that, in anticipation of NDPSC consideration in February 2005, he refer the “in principle” recommendation to MCC for consideration.

OUTCOME

The NDPSC agreed with the TTHWP’s assessment and on the grounds of harmonisation, the Committee agreed to recommend to the New Zealand Ministry of Health that based on a history of safe use and in the interests of harmonisation, the 10 gram pack size of 5% acyclovir products within the general sales classification be harmonised with Australia.

1.8.1.2.3 HYOSCINE BUTYLBROMIDE

PURPOSE

The Committee considered the harmonisation of the scheduling of hyoscine butylbromide with New Zealand.

BACKGROUND

In May 1998, the NDPSC considered a submission from XXXXXXXXX requesting that hyoscine butylbromide 10 mg tablets when in pack sizes of 20 tablets or less be rescheduled from Schedule 3 to Schedule 2. Hyoscine butylbromide had been first placed in Schedule 4 in 1967 and on the basis of a submission from the sponsor, had been rescheduled to Schedule 3 in November 1994.

The Company considered that Schedule 2 was justified on the grounds of its wide safety margin in therapeutic use and overdose, its use in conditions the consumer could easily

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recognise and that the small pack size reduced the potential for the masking of more serious conditions.

The NDPSC also considered comment received during the pre-meeting public consultation period from XXXXXXXXX in support of the proposal and XXXXXXXXX and XXXXXXXXX opposing the proposal.

Two issues in regard to the availability of hyoscine butylbromide in small pack sizes were considered by the NDPSC to be particularly relevant to the Schedule 2 proposal. The first was in regard to consistency with the current SUSDP entries for the belladonna alkaloids. The Committee recognised that the Schedule 2 availability of other forms of hyoscine and related alkaloids, which had arguably a worse adverse effect profile that hyoscine butylbromide could be considered a justification for rescheduling. The Committee noted that hyoscine butylbromide, and other quaternary derivatives of hyoscine, were not well absorbed from the gastrointestinal tract and did not readily pass the blood brain barrier, unlike other forms of hyoscine. Therefore, central nervous system adverse effects were rare. Further, reports of abuse of hyoscine preparations did not implicate hyoscine butylbromide.

The NDPSC had considered a review of the solanaceous alkaloids at its February 1995 Meeting. The Committee had agreed that, on the information available in regard to abuse, mis-use or serious adverse effects with the Schedule 2 products and of satisfaction expressed by jurisdictional members with the entries, amendment to the entries was not required.

The second issue was in regard to the ability of the patient to accurately self-diagnose and use the product appropriately without the need for advice from the pharmacist. One Member advised that the current pharmacy experience with XXXXXXXXX was that S3 sales were usually follow-up sales to a customer where the initial purchase had been under the direction of a medical practitioner. In those cases where a sale may be on the recommendation of a pharmacist, the usual practice was to give instructions that the customer should seek medical advice within 24 hours if no improvement in condition occurred.

Several NDPSC Members were not satisfied that the consumer would be able to accurately diagnose their condition to ensure appropriate use of the product without advice from the pharmacist. The Committee noted that 'the correct interpretation of acute abdominal pain was one of the most challenging demands made on a physician' (Harrisons Principles of Internal Medicine).

It was recognised that the hyoscine butylbromide is marketed for the treatment of irritable bowel syndrome and the ability of the consumer to adequately self-diagnose this condition was questioned. It was recognised that this expertise may be outside the expertise of the pharmacist. However the pharmacist was in the position to advise the consumer to seek medical help if no relief were obtained. Irritable bowel syndrome was considered to be covered by the wording of the approved indication ' spasm of the

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gastrointestinal tract', and a Member recalled that in the past the Committee had not been comfortable with irritable bowel syndrome being a Schedule 2 indication.

The NDPSC considered that Schedule 3 remained appropriate.

In August 1998, the Company addressed the Committee’s concern in regard to appropriate use of the preparation without pharmacist intervention. It noted that hyoscine butylbromide without a prescription was indicated for the treatment of acute conditions only, and that the 20 pack of tablets (Schedule 3 pack size) was not indicated or marketed for the non-acute condition of irritable bowel syndrome.

The NDPSC considered that its major concern in regard to inappropriate use had been addressed. The view was expressed that Schedule 3 was possibly more appropriate for both the current Schedule 2 preparations and hyoscine butylbromide but it was considered that the long history of the alkaloids in Schedule 2 precluded such a change at this time, without seeking further information.

Therefore, the NDPSC supported the rescheduling of hyoscine butylbromide from Schedule 3 to Schedule 2.

In considering proposals for harmonisation of scheduling, the New Zealand MCC had expressed concerns similar to those addressed by the NDPSC in its discussion in relation to the Schedule 2 proposal, viz the need for consultation over abdominal pain. MCC members agreed misdiagnosis was easy and there was danger, even with a 4-day pack, that the product could be used with acute appendicitis, renal stones or gastric ulcers and that bowel problems could be masked. There were also concerns associated with cardiac arrhythmia and glaucoma and with interactions with other medicines.

MCC had continued to maintain its reservation about any change in scheduling. NDPSC considered that their concerns had been adequately dealt with in the labelling of the product and were satisfied to accept a more general indication of non-specific spasm of the gut rather than a series of specific indications including irritable bowel syndrome.

DISCUSSION

NDPSC noted that the Trans-Tasman Harmonisation Working Party had confirmed that the approved product indication for XXXXXXXXX was for “Spasm of the gastrointestinal tract”. Label indications are “For the relief of stomach ache and pain due to cramp or spasm: … provides relief from the pain and discomfort of stomach cramps and spasm”. Schedule 2 products available in Australia were in pack sizes of 10.

To help establish the safety position with hyoscine butylbromide in Australia, the ADRAC had been requested to undertake an analysis of adverse reactions. ADRAC advised that they held 120 adverse drug reaction case reports for hyoscine butylbromide, with 16 case reports where the oral route of administration was specified. A total of 29

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reaction terms were contained in the 16 case reports. Summary data for all formulations and for oral formulations respectively were provided.

There were no reports where XXXXXXXXX or XXXXXXXXX were specifically identified. The 16 reports for oral hyoscine butylbromide were identified either as XXXXXXXXX or hyoscine butylbromide tablets. Serious adverse reactions reported included one report each for cardiac failure, ileus paralytic, intestinal perforation, hepatitis, sepsis, neuroleptic malignant syndrome, confusional state and urinary retention.

The Working Party’s advice to NDPSC was that, having regard to the established safety in use of products containing hyoscine butylbromide over an extensive period and in the interests of harmonisation, that the New Zealand Ministry of Health reconsider harmonisation of scheduling with the SUSDP.

OUTCOME

The Committees agreed to recommend to the New Zealand Ministry of Health that, on the grounds of harmonisation and based on an established safety record, the scheduling of hyoscine butylbromide be harmonised with the SUSDP.

1.8.1.2.4 JUNIPERUS SABINE/SAVIN OIL

PURPOSE

The Committee considered the harmonisation of scheduling of Juniperus sabina/savin oil.

BACKGROUND

At its 4th meeting in June 1999, the TTHWP advised the NDPSC that it should recommend to the New Zealand Ministry of Health that, on the grounds of public health, consideration should be given to rescheduling savin oil from Part I to Part II.

The New Zealand MCC considered the issue at its December 2001 meeting and noted that savin oil was already classified as a prescription medicine. The Committee agreed that Juniperus sabina should also be classified as a prescription medicine at all strengths to harmonise with the Australian Appendix C scheduling.

At its May 2002 meeting, the MCC further considered the reclassification of Juniperus sabine to prescription medicine status. The MCC noted that savin oil was already classified as a prescription medicine which meant that it was unavailable for use in complementary medicines. However, it was thought that there might be complementary medicines on the New Zealand market which were derived from parts of the plant other than the essential oil. MCC agreed that changing the name to Juniperus sabina could increase the scope of the substance to be classified and deny access to products to which the Committee did not wish to restrict at this point in time. It was therefore agreed that the entry for savin oil should remain unchanged in the schedule.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 12

In June 2004, the TTHWP noted that some products available in New Zealand or Australia were likely to be based on the oil while others could be based on the plant. The Working Party was uncertain as to whether the toxic moiety was the oil or the whole plant and requested that the Secretariat seek to determine the basis for the Appendix C classification in the SUSDP. XXXXXXXXX noted that if it was determined that the whole plant was toxic, then changes to the classification in New Zealand might be considered. It was further noted however, that a change in nomenclature might not by itself bring about harmonisation as savin oil was available only on prescription in New Zealand while Juniperus sabine was listed in Appendix C in the SUSDP. Inclusion of Appendix C entries in the New Zealand Part I classification were, however, regarded as essentially harmonised.

The Working Party requested the Secretary to seek advice from the Office of Complementary Medicines (OCM) in regard to:

• the toxicity of the Juniperus sabine plant, • whether there were products based on Juniperus sabine available in Australia, and • whether there was a distinction between the oil and parts of the plant. OCM was also to be asked to identify other plants that were used in Australia. The New Zealand representative also undertook to identify uses of the oil and other parts of the plant in New Zealand as well as provide information on the concentration of savin oil/plant in products and indications for use.

DISCUSSION

The Committee noted advice from the OCM that the oil and all parts of the plant could be used in complementary medicines. Both the plant (various components) and the oil were extremely toxic and could have variable toxicity depending on age and storage. This would suggest that, in regard to medicines and the present position in both New Zealand and Australia, that products containing Juniperus sabine or savin oil should not be available. The TTHWP had noted that it may therefore be more appropriate to schedule on the basis of the plant. New Zealand harmonisation of nomenclature (Part I) with Appendix C in the SUSDP would result in an “essentially harmonised” situation.

An alternative approach to achieve harmonisation considered by the Working Party and which would have less impact upon existing homeopathic medicines was to retain the Appendix C entry and establish a cut-off level for Juniperus sabina in Appendix G similar to the approach adopted for Croton Tiglium. Based upon the only existing product in the Australian market, and OCM advice that products based on Juniperus sabina are only permitted where the “potency” of the ingredient is 12X or greater, the cut off level for Juniperus sabina would have to be set at the femtogram level. To achieve harmonisation, New Zealand would then need to consider a corresponding cut-off level to exempt homeopathic products from ‘Prescription Only’ classification. The practicality of exemptions at this level was questioned.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 13

The NDPSC noted the Working Party advice that Juniper Berry oil had been considered by NDPSC as part of its review of essential oils. However there appeared to have been no consideration given to the appropriateness of scheduling Juniperus species.

OUTCOME

The NDPSC concurred with the advice of the TTHWP and agreed to recommend to the New Zealand Ministry of Health that, having regard to the toxicity of the Juniperus sabina plant and in order to achieve harmonisation with the SUSDP, the New Zealand Ministry of Health consider replacing its Part 1 scheduling of savin oil with a Part 1 entry for Juniperus Sabina.

1.8.1.2.5 NICOTINE IN NRT

PURPOSE

The Committee considered the harmonisation of the scheduling of nicotine in nicotine replacement therapy.

BACKGROUND

At its November 2000 meeting, following a recommendation from the Trans Tasman Harmonisation Working Party, the NDPSC considered whether de-scheduling of nicotine in gums and patches met with the criteria for such a change. At that time NDPSC agreed not to change the scheduling of nicotine. The NCCTG guidelines required the NDPSC to reconsider this matter again after two years.

This matter was again considered by the NDPSC in October 2003. Following consideration of pre-meeting submissions from a variety of stakeholders and consideration of relevant studies, as well as comparisons of the regulatory situations in Australia and New Zealand, the NDPSC agreed to exempt nicotine in gums and transdermal patches from the requirements of scheduling. The reasons for this decision were that widening the availability of NRT products would encourage more smokers to quit smoking and that this would lead to improved public health outcomes. The Committee also noted that the decision harmonised the scheduling outcome with New Zealand.

The NDPSC October 2003 meeting also agreed to consider the proposal to exempt lozenges from scheduling requirements for consistency with nicotine in chewing gum and transdermal patches. The NDPSC February 2004 meeting subsequently agreed to exempt nicotine lozenges.

However, the New Zealand MCC at its November 2003 meeting took the decision to reclassify nicotine lozenges from restricted medicine to pharmacy-only medicine. The Committee also considered nicotine sublingual tablets. These had been restricted medicines but were not included in the NDPSC recommendation, possibly because they

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 14

were not available in Australia. In New Zealand, lozenges and sublingual tablets had initially been classified as restricted medicines as there had been insufficient data on usage experience available at the time to warrant a less restrictive level of classification. The MCC took the decision that nicotine in lozenges and sublingual tablets be reclassified from restricted medicine to pharmacy-only medicine.

At its June 2004 meeting, the NDPSC considered and endorsed a proposal to reschedule nicotine in sublingual tablets for Nicotine Replacement Therapy from Schedule 3 to Schedule 2 in the SUSDP. At that time, this decision resulted in harmonisation between Australia and New Zealand.

DISCUSSION

The NDPSC noted that the respective actions of the New Zealand MCC (prior to its most recent November 2004 meeting) and the NDPSC, including the decision to include nicotine sublingual tablet preparations in Schedule 2, had now resulted in the approach to the scheduling of nicotine in Nicotine Replacement Therapy being harmonised with the exception of lozenges, which in New Zealand were classified as a ‘Pharmacy Only’ medicine.

NDPSC also recalled that in New Zealand, lozenges and sub-lingual tablets had initially been classified as restricted medicines as there had been insufficient data on usage experience available at the time to warrant a less restrictive level of classification. MCC had been concerned that the safety profile of lozenges and sub-lingual tablets might differ from that of nicotine in patches and gum because of their different release characteristics. MCC also had concern about consumption by children. In New Zealand, ‘Pharmacy- Only’ nicotine products can be sold from a smoking cessation clinic run under the auspices of a registered medical practitioner, nurse, pharmacist or psychologist.

On the basis of experience to date with the availability in New Zealand of lozenges as a ‘Pharmacy Only’ medicine, the need to broaden options for smoking cessation and in the interests of harmonisation, it was agreed that the MCC should be asked to consider including lozenges as a ‘General Sales’ medicine. This would result in harmonisation of scheduling for nicotine across all NRT product forms.

However, at the November 2004 meeting of the New Zealand Medicines Classification Committee, MCC recommended that nicotine in medicines for smoking cessation should be reclassified from pharmacy-only medicine to general sale medicine when in lozenges or sublingual tablets. As a result, the scheduling of sublingual tablets were now unharmonised between Australia (S2) and New Zealand (general sale).

TTHWP agreed that scheduling of the sublingual tablets should be harmonised with the most recent New Zealand decision ie that sublingual tablets be exempt from scheduling.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 15

OUTCOME

The Committee agreed that, on the grounds of harmonisation with New Zealand, nicotine in sublingual tablets be exempt from scheduling requirements.

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Schedule 2 - Amendment

NICOTINE – amend entry to read:

NICOTINE for use as an aid in withdrawal from tobacco smoking in preparations for inhalation.

Schedule 4 - Amendment

NICOTINE – amend entry to read:

NICOTINE for use as an aid in withdrawal from tobacco smoking (including preparations for nasal administration) except:

(a) when included in Schedule 2;

(b) in chewing gum;

(c) in lozenges;

(d) for sublingual use; or

(e) in preparations for transdermal use.

Schedule 7 - Amendment

NICOTINE – amend entry to read:

NICOTINE except:

(a) when included in Schedule 2,4 or 6;

(b) in chewing gum;

(c) in lozenges;

(d) for sublingual use;

(e) in preparations for transdermal use; or

(f) in tobacco prepared and packed for smoking.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 16

1.8.1.2.6 ALCLOMETASONE AND CLOBETASONE

PURPOSE

The Committee considered the harmonisation of the scheduling of alclometasone and clobetasone.

BACKGROUND

Alclometasone

The February 2000 NDPSC Meeting agreed that alclometasone in preparations for dermal use containing 0.05 per cent or less of alclometasone in packs containing 30 g or less of such preparations be rescheduled from S4 to S3. The NDPSC subsequently forwarded a recommendation to the New Zealand MCC to consider adopting a similar outcome. However, this proposal was rejected by the MCC on the advice of XXXXXXXXX that the S4 classification remained appropriate. The May 2001 NDPSC Meeting reconsidered its decision at the request of the New Zealand MCC, and agreed to seek expert advice.

The NDPSC received advice from ADEC which noted that:

• there was a concern over the absence of reliable safety data on the long-term use of topical alclometasone. • aclometasone had a high degree of vasoconstricting efficacy, which could correlate with significant potency and potential for local side effects. • a number of reports had suggested that alclometasone had similar profile to clobetasone, an extremely potent topical steroid. • the applicant should provide evidence of long-term safety before this agent was released as an OTC medication. The NDPSC also noted advice from the ADRAC that there had been 4 adverse reports associated with topical alclometasone (XXXXXXXXX) between 1988-1996, all of which were minor and application site reactions occurring after short periods of use (less than a week).

The NDPSC was advised that New Zealand had made a policy decision to require compelling evidence to support rescheduling applications to OTC use of topical corticosteroids where the potency was greater than that of 1% hydrocortisone. This was stated to be part of the strategy to create a “treatment ladder” in New Zealand, and was considered essential to promote appropriate use of medicines. In addition, the Member suggested that the pattern and level of usage of corticosteroids in New Zealand was different to Australia, on the basis of policy and pricing variations.

The NDPSC agreed not to harmonise with the New Zealand scheduling of alclometasone and review the scheduling of clobetasone at the February 2002 meeting.

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The Committee further agreed that the existing Schedule 3 listing for dermal preparations containing 0.05% or less alclometasone for use in humans remained appropriate. This decision was made on the basis that there was sufficient evidence to demonstrate that the safety profile and pattern of use of such preparations justified their continued availability as an S3 medicine.

Clobetasone

In forwarding a pre- November 2001 meeting submission relating to alclometasone, XXXXXXXXX included a proposal that the NDPSC consider rescheduling from S4 to S3, dermal preparations containing 0.05% or less of clobetasone in packs containing 30 g or less. XXXXXXXXX had argued that clobetasone was in the same class as alclometasone, being a moderately potent corticosteroid. Furthermore, XXXXXXXXX forwarded an additional proposal prior to the February 2002 meeting, seeking to include clobetasone in Appendix H of the SUSDP – Schedule 3 poisons permitted to be advertised.

XXXXXXXXX had planned to market a product in Australia, XXXXXXXXX, containing 0.05% clobetasone butyrate in a pack size of 30 g. The proposed indication was for short-term treatment (7 days) and control of patches of eczema and dermatitis, including atopic and seborrhoeic eczema, and primary irritant and allergic dermatitis on certain areas of the body for use in adults and children over 12 years of age. Following the November 2001 meeting, XXXXXXXXX was advised that the Committee had deferred consideration of its proposal relating to clobetasone to the February 2002 meeting, to allow a proper evaluation of its submission.

No product containing clobetasone was listed on the ARTG or PUBCRIS. The Medsafe database listed dermal preparations (cream and ointment) containing 0.05% clobetasone in 30 g and 100 g tubes.

The NDPSC noted comments from XXXXXXXXX and also the TGA evaluation report which supported the proposal that dermal preparations containing 0.05% or less of clobetasone in packs containing 30 g or less, be rescheduled to S3.

The NDPSC recalled that it did not adopt the New Zealand MCC recommendation to reinstate in S4, preparations containing 0.05% alclometasone for dermal use. Members were reminded that the NDPSC proceeded to confirm the S3 scheduling of 0.05% alclometasone for dermal use, on the basis that there was sufficient evidence to demonstrate that the safety profile and pattern of use of such preparations justified their continued availability as S3.

The NDPSC was advised that the relative potencies of clobetasone and alclometasone were comparable, and that the safety profile and efficacy of 0.05% alclometasone is similar to 1% hydrocortisone. Accordingly, alclometasone was also approved for use in children under 2 years old. It was noted that whilst clobetasone has comparable side

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 18

effect profile to 1% hydrocortisone cream, the XXXXXXXXX submission was based on the proposed use of 0.05% clobetasone in adults and children 12 years and over.

DISCUSSION

The February 2005 meeting of the NDPSC noted advice from the Trans-Tasman Harmonisation Working Party that in Australia there were no products containing clobetasone listed on the ARTG. The Medsafe database listed dermal preparations (cream) containing 0.05% clobetasone in 30 g tubes and dermal preparations (cream and ointment) containing 0.05% alclometasone in 30 and 100 g tubes.

The Working Party advised that the concerns raised by XXXXXXXXX had related to:

• the use of “intermediate strength” corticosteroids, including alclometasone. The Society considered that OTC sale would increase the range of products available and cause confusion about appropriate use. • stronger preparations may follow – the thin edge of the wedge. • increased and unnecessary use arising from a perception that the products were better than hydrocortisone. • side effects which it was said had been had been observed including thinning of the skin, steroid induced perioral dermatitis and steroid induced rosacea. • inappropriate use of steroids which would exacerbate other skin conditions and mask the diagnosis of some. • reservations about use in children and the elderly. A literature search specific to the safety of alclometasone and clobetasone confirmed that they were of low to mild potency. A review of the clinical efficacy and safety of clobetasone butyrate cream noted that, in the UK, clobetasone cream (0.05%) was available as a pharmacy medication for the short-term management of acute eczema and allergic dermititis by adults and children aged 10 or older. Clinical trials involving in excess of 3500 patients had confirmed that short-term clobetasone use resulted in no clinical significant difference between hydrocortisone 1.0% in terms of skin thinning and even under extreme conditions, clobetasone had negligible systemic absorption and almost no effect on HPA axis function.

The review also noted that topical steroid creams and ointments had been available as OTC medicines for more than 10 years without clinically significant adverse effects. The paper also commented that in the UK, most patients were treated by general practitioners rather than dermatologists and that once their skin condition was recognised, the availability of OTC treatment were advantageous in allowing flare-ups to be quickly controlled.

A review on the safe use of topical corticosteroids in children noted that “serious side effects from the use of topical corticosteroids had rarely been reported in children.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 19

However, as preparations of greater potency had become available, the potential for side effects had increased". It also noted that short-term use of mild to moderately potent topical corticosteroids had no clinically significant effects on the cortisol level in the plasma of children.

The New Zealand Ministry of Health assessment report associated with the proposal to reschedule clobetasone from Schedule 4 to Schedule 3 also generally supported the above and concluded that “Eumovate is a moderately potent steroid with less potential for adverse effects such as systemic absorption and skin thinning than the potent steroids. There has been extensive use and relatively few spontaneous adverse reports, so the evidence points to relative safety”. However, the rescheduling was denied. The Australian Drug Evaluation Committee reached a similar conclusion.

The NDPSC noted that the Working Party had also received advice from ADRAC that they had not received any significant reports of adverse effects.

The NDPSC noted recommendations from the November 2004 MCC meeting which, if adopted, would result in harmonisation between Australia and New Zealand. The New Zealand MCC had agreed to recommend:

• that 0.05% topical preparations of alclometasone and clobetasone should be placed on the agenda of the next meeting for consideration for classification to restricted medicine • that the respective sponsor companies be asked if they wished to submit comments in support or otherwise of the proposed reclassification. OUTCOME

The Committee agreed to recommend to the New Zealand Ministry of Health that, on the basis of established safety in use and to achieve harmonisation, alclometasone and clobetasone be rescheduled to restricted medicine (Schedule 3).

1.8.1.2.7 HYOSCINE AND HYOSCYAMINE

PURPOSE

The Committee considered harmonising the cut-off to exempt concentrations in Appendix G for hyoscine and hyoscyamine.

BACKGROUND

At the June 2003 meeting of the NDPSC, the Committee considered the cut-off values (Appendix G) for solanaceous alkaloids.

The NDPSC noted that the November 2002 New Zealand MCC Meeting considered a submission from XXXXXXXXX proposing to raise the cut-offs from scheduling

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 20

requirements for dilute preparations of solanaceous alkaloids on the grounds that they were too low for the plant alkaloids. XXXXXXXXX 's proposal had been based on the principle where herbal medicines containing one hundredth of the minimum lethal dose of solanaceous alkaloids per pack could be sold as “general sale”. The MCC considered this approach appropriate from a safety perspective and agreed that raising the cut-off for exemption to 300 mcg per litre or per kilo for atropine, hyoscine and hyoscyamine in 'general sale' homeopathic preparations still provided a 100-fold safety factor. The MCC also noted that the existing inconsistency in the New Zealand Schedules, where the cut- offs for exemption applied to both the plant material and its alkaloids were being amended to express these cut-offs in terms of the total alkaloid content.

The NDPSC was informed that XXXXXXXXX’s submission to the New Zealand MCC outlined the active principle levels, toxic levels and therapeutic levels with regards to solanaceous alkaloids with the proposed cut-off’s based on 1/100 of the minimum lethal dose. The references submitted by XXXXXXXXX concerning toxic doses related to atropine only. Fatal doses of atropine were reported at as low as 1.6 mg and as high as 100 mg in children. If atropine was at a concentration of 300 micrograms per litre, a child would need to consume a quantity in excess of 5 litres to reach the fatal dose of 1.6 mg, while an adult would need to consume considerably more. The submission stated that XXXXXXXXX supplied their products in both 30 ml and 100 ml pack sizes. If the concentration of these products were 300 micrograms of atropine per litre, over 50 bottles of the 100 ml pack size would need to be consumed with the number increasing to over 160 bottles for the 30 ml pack size to reach the fatal dose for a child of 1.6 mg. The proposed Appendix G cut-off to exempt of 300 micrograms of atropine would allow for the maximum SUSDP listed Schedule 2 oral dose in one litre of preparation.

The NDPSC considered XXXXXXXXX’s rationale, which supported the maximum SUSDP listed Schedule 2 oral dose in one litre of preparation or 300 micrograms/L, to be an appropriate cut-off for atropine in Appendix G of the SUSDP.

However, the NDPSC also noted that the current cut-off’s for atropine, hyoscine and hyoscyamine in Appendix G did not reflect the relative potencies of atropine and hyoscine and hyoscyamine. Members noted that Martindale reported hyoscyamine as having twice the antimuscarinic potency of atropine and that hyoscine was a more powerful suppressant of salivation than atropine. Given the increased potency of hyoscyamine and hyoscine, the Committee based the cut-off’s for these substances on a level that is half that of the cut-off for atropine or 150 micrograms/L.

The NDPSC agreed to amend the cut-off in Appendix G of the SUSDP for atropine to harmonise with New Zealand. However, it was agreed to amend the cut-off’s for hyoscine and hyoscyamine at half that of atropine based on their increased toxicity relative to atropine. Consequently harmonisation was not achieved for hyoscine and hyoscyamine.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 21

DISCUSSION

The Committee agreed that the XXXXXXXXX argument, namely that if atropine was at a concentration of 300 micrograms per litre, a child would need to consume a quantity in excess of 5 litres to reach the fatal dose of 1.6 mg, while an adult would need to consume considerably more, was also applicable to hyoscine and hyoscyamine and demonstrated a considerable safety margin that would allow the cut-off to exempt for hyoscine and hyoscyamine as outlined in Appendix G of the SUSDP be amended to 300 micrograms.

OUTCOME

The Committee agreed that on the basis of safety and to promote harmonisation with New Zealand, that the cut-off to exempt for hyoscine and hyoscyamine as outlined in Appendix G of the SUSDP be amended to 300 micrograms.

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Appendix G - Amendment

HYOSCINE – amend entry to read:

HYOSCINE 300 mg

HYOSCYAMINE – amend entry to read:

HYOSCYAMINE 300 mg

1.8.1.2.8 PARACETAMOL 665 MG

PURPOSE

The Committee considered progress towards the harmonisation of scheduling for paracetamol 665 mg products.

BACKGROUND

The October 2001 meeting of the TTHWP had agreed to a process leading to harmonisation of entries for paracetamol in 2004 based on foreshadowing changes including the removal of the reverse scheduling warning statements following the handover by the NDPSC of Appendix F warning statements for therapeutic goods to the TGA.

New Zealand had advised that paracetamol 665 mg had already been considered by MCC. They had agreed to differ on the upper limit for OTC sale and had retained the 500mg per dose form upper limit. New Zealand had also agreed to increase pack sizes to 12.5 grams to harmonise with Australia. However, there were conditions attached

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relating to pack warnings which were suitable to both countries. It appeared that these pack warnings had not yet been finalised.

New Zealand had advised that it was to review regulatory standards and labelling standards for paracetamol before further addressing the harmonisation of scheduling. In that regard, the TGA OTC Medicines Section advised that revised regulatory guidelines for paracetamol would be developed for the Joint Agency. The document “Required Advisory Statements for Medicine Labels” was issued in July 2004. On this basis, the TTHWP recommended that the scheduling of paracetamol 665 mg be referred to the New Zealand MCC for consideration.

DISCUSSION

The NDPSC noted that the “Required Advisory Statements for Medicine Labels” had now been issued, and, accepting the advice of the TTHWP, agreed that the scheduling of paracetamol 665 mg product again be referred to MCC for consideration in respect to harmonisation with the SUSDP.

OUTCOME

The Committee agreed that having regard to safety and in the interests of harmonisation, that the New Zealand Ministry of Health again be requested to consider harmonising the scheduling of paracetamol 665 mg.

1.8.1.2.9 IBUPROFEN

PURPOSE

The Committee noted progress towards harmonisation of the scheduling of ibuprofen and in particular, the harmonisation of the concentration in liquid ibuprofen for OTC sale.

BACKGROUND

The November 2000 meeting of TTHWP recommended that the New Zealand Ministry of Health adopt the revised wording of the SUSDP (15) (2) amendment for ibuprofen that:

• set an upper daily dose for divided and undivided preparations for ibuprofen; and • relaxed the concentration requirements for ibuprofen liquid preparations, but retained a 4g total content of ibuprofen in these packs. The May 2002 meeting of MCC considered the TTHWP recommendation and agreed that:

• the maximum daily dose for pharmacy-only solid dose and liquid ibuprofen should not exceed 1200 milligrams.

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• the maximum pack size for pharmacy-only liquid preparations should not exceed 4 grams of total ibuprofen content. • packs of undivided preparations for pharmacy-only sale should be in concentrations only of 100mg in 5mL or 200mg in 5mL of ibuprofen. • the NDPSC adopt the MCC recommendation limiting the concentrations of liquid ibuprofen permitted in pharmacy-only (S2) medicines. The October 2002 meeting of NDPSC agreed to gazette the consideration of scheduling of ibuprofen for consideration at the February 2003 meeting.

The NDPSC noted that there was harmonisation on pack size. However, New Zealand had adopted dose limitations into their Regulatory Guidelines and New Zealand MCC were recommending harmonisation on strengths.

The NDPSC agreed that the Schedule 2 entry for ibuprofen remained appropriate and that the scheduling of ibuprofen (in respect to liquid preparations and strength) would remain unharmonised at this time.

New Zealand had subsequently taken the position that requirements for OTC ibuprofen arising from recent harmonisation recommendations had become too lengthy to be specified clearly in the First Schedule to the Medicines Regulations. It had therefore been decided that a more practical approach would be to require all OTC ibuprofen in both solid and liquid forms to be sold in the manufacturer's original pack and to list the strength, pack size and dose requirements in the new Zealand Regulatory Guidelines. The update to the guidelines would be included in the next edition.

New Zealand did not envisaged that this changed approach to scheduling solid dose OTC ibuprofen would have any effect on products already on the market. There would, however, be some relaxation in the availability of liquid dose forms. New Zealand labelling requirements are as per the MEC Labelling Guidelines

DISCUSSION

The NDPSC noted the advice of the Working Party that in regard to liquid forms, the MCC had agreed that the intention to reclassify liquid ibuprofen to pharmacy-only medicine had been for paediatric doses only. Liquid ibuprofen had not been intended to be available at this level for chronic use. The position adopted by the MCC would allow the same paediatric doses to be available but would also permit smaller volumes of more concentrated products. While wishing to retain the proposal to limit the total pack content to 4 grams, the MCC also wished to place limits on the concentration permitted for pharmacy-only sale which would maintain consistency with pharmacy-only solid dose forms. MCC had therefore agreed that concentrations only of 100 milligrams in 5 millilitres and 200 milligrams in 5 millilitres should be available as pharmacy-only medicines.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 24

It was also noted that, while the SUSDP did not specify specific concentrations for liquid preparations (although in the past this was the case), the 4 gram upper limit on pack size ensured that the possibility of, for example, accidental poisoning or overdose was minimised. In Australia, products in the market are 50ml, 100 ml or 200 ml (with the 4 gram limit). The outcome of scheduling was therefore the same in both countries and on that basis it could be regarded that the situation is “essentially harmonised”.

The Committee was advised that in considering the proposal for the scheduling of XXXXXXXXX, the NDPSC at its November 1998 meeting had noted that the issue of overdose had been addressed in the submission. At that time, the Company advised that the UK National Poisons Information Service data indicated that in ibuprofen overdose in children, 75-85% of cases remained asymptomatic (the product had been marketed without prescription in the UK since 1989). The NDPSC had considered that in the event of accidental ingestion in a very small young child, the safety profile of ibuprofen was still likely to be not inferior, and potentially superior, to that of paracetamol suspension. The usual symptoms associated with overdose in the young were nausea, vomiting, abdominal pain, headache, lethargy, nystagmus, diplopia and blurred vision. The Committee noted that there was no estimated fatal dose of ibuprofen, compared to paracetamol and aspirin for which 15 g and 25 g respectively are considered potentially fatal doses. (The maximum amount available for ingestion in the product is 4g).

OUTCOME

The Committee noted that the scheduling of ibuprofen was now essentially harmonised.

1.8.1.3.1 STRYCHNOS SPP

PURPOSE

The Committee considered the harmonisation of the scheduling of Strychnos spp, particularly the cut-off for exemption from scheduling of dilute preparations containing Strychnos spp.

BACKGROUND

At the October 2004 meeting of NDPSC, the Committee noted that the 11th TTHWP meeting had identified that the differences between scheduling of Strychnos spp in Australia and New Zealand centred around the cut-off for exemption for Strychnos spp. In Australia the cut-off for exemption was 10 mg/kg whereas in the New Zealand classification, the cut-off for exemption for Strychnos spp. was based on strychnine and set at 1 mg/kg or litre. Strychnine was not separately listed in the schedules in New Zealand.

To achieve the least restrictive approach to harmonisation, the TTHWP identified that New Zealand would need to consider amending the classification to exempt products containing 10 milligram or less per kilogram or litre of Strychnos spp. At the same time,

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 25

the TTHWP noted that, from a compliance and enforcement perspective, it would be preferable to specify the cut-off in terms of the alkaloid content, ie strychnine.

The TTHWP had agreed to recommend to the NDPSC that the New Zealand Ministry of Health (MOH) consider harmonising with Australia by adopting the least restrictive approach to scheduling viz to adopt the Australian scheduling and set the cut-off level at 10 mg/kg or litre of Strychnos spp. However, prior to consideration of the matter at the October 2004 NDPSC meeting, the TTHWP initiated further research in respect to the level of strychnine in strychnos spp and sought any evidence of adverse health effects associated with the use of Strychnos spp.

DISCUSSION

The Committee recalled that, at the October 2004 NDPSC meeting, it was noted that since the June 2004 TTHWP meeting, advice had been received in respect to the strychnine content of Strychnos spp and also information about the safety of strychnos spp products. The Office of Complementary Medicines (OCM) had advised that, within Australia, only Strychnos nux-vomica and Strychnos ignatii were permitted for use in complementary medicines. OCM had also advised the strychnine content of Strychnos spp.

The Committee considered that, while the TTHWP had recommended harmonisation based on 10 mg/kg strychnos spp, ie the least restrictive approach, it might be preferable that harmonisation take into account the preference from a compliance perspective to harmonise on strychnine and not the plant species. This would avoid uncertainties in compliance arising from different levels of strychnine in various plant parts and across species.

The Committee also noted advice from OCM in respect to the strychnine content of the mother tinctures (the mother tincture is the original herbal tincture which is subsequently diluted and succussed to make homoeopathic potencies), of Nux vomica. The French Pharmacopoeia dictated a minimum level of 0.12 per cent, and a maximum level of 0.13 per cent strychnine. The German Homoeopathic Pharmacopoeia dictated a minimum of 0.18 per cent and a maximum of 0.2 per cent of strychnine and brucine, of which not more than 55 per cent of the homeopathic mixture is strychnine, in the mother tincture.

OCM had also commented that under current Australian regulations for homeopathic medicines, any homeopathic preparation that is a 1000 fold dilution (or a lesser dilution) of the mother tincture is required to be Listed on the ARTG. Any remedy more dilute than this was therefore likely to have a maximum of 0.000013 per cent strychnine, which was below the maximum permitted cut-off level. There was also a wide safety margin compared against reported low-level fatal doses and the accepted lethal dose.

The Committee recalled that it had foreshadowed the harmonisation of the scheduling of Strychnos spp with New Zealand, proposing deleting the Appendix G entry for Strychnos spp and amending the Schedule 4 entry in line with the New Zealand classification. The

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 26

foreshadowed decision had been included in the pre-meeting Gazette Notice for the February 2005 meeting. Comments were received from XXXXXXXXX and XXXXXXXXX.

XXXXXXXXX supported the proposal and had no specific comment to make. However, XXXXXXXXX reserved the right to make further comment should there be changes to the proposal as a result of consultation.

XXXXXXXXX supported the foreshadowed decision. XXXXXXXXX noted that the German Homoeopathic Pharmacopoeia gave the limits as “The Mother tincture contains not less than 0.18 and not more than 0.27 percent of overall of strychnine and brucine …..”

DECISION 2005/43 – 1

The Committee agreed to harmonise the scheduling of Strychnos spp with New Zealand by deleting the Appendix G entry for Strychnos spp and amending the Schedule 4 cut-off in line with the New Zealand classification.

Schedule 4 - Amendment

STRYCHNOS spp – amend entry to read:

STRYCHNOS spp except in preparations containing 1 milligram or less per litre or per kilogram of strychnine.

Appendix G - Amendment

STRYCHNOS spp – delete entry

1.8.1.4 OUTCOMES FROM TTHWP 13TH MEETING

PURPOSE

The Committee considered the following:

• foreshadowed amendments to substances in the SUSDP in order to achieve harmonisation in medicines scheduling arising from the 13th TTHWP meeting, • XXXXXXXXX, • the need to maintain the TTHWP and the revised membership beyond June 2005.

BACKGROUND

The Trans-Tasman Harmonisation Working Party (TTHWP) presented a summary paper highlighting the outcomes of its most recent (13th) meeting which had been held on

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 27

21 February 2005, ie prior to NDPSC (43). Following a review of all Schedule 2 and 3 substances in cooperation with New Zealand, the Working Party had identified for NDPSC, those substances where the scheduling in Australia and New Zealand was not harmonised. Subject to agreement by New Zealand, the Working Party recommended to the NDPSC that it foreshadow through Gazettal prior to the June 2005 meeting, amendments to the SUSDP in order to achieve harmonisation.

The Working Party also noted that, due to impending retirement, XXXXXXXXX would not be available after the next meeting of the Working Party in June 2005. A replacement would be necessary to ensure continuity of the work program.

The Working Party also noted the need for maintaining the momentum towards harmonisation and therefore the importance of the continuation of the Working Party. It was proposed that the TTHWP be reaffirmed, including budget and revised membership, by the NCCTG.

DISCUSSION

The NDPSC noted that the Working Party had proposed a policy position that, where there were S2/S3 entries but no products included on the ARTG or on the New Zealand SMARTI, those scheduling entries should be deleted but the parent entry should be retained/added in Schedule 4.

The Committee recalled that the principles of harmonisation of scheduling of drugs and poisons established by the NCCTG stated in part, that the underlying principle was to harmonise on the least restrictive schedule while giving due consideration to public health and safety issues and/or specific jurisdictional needs. While the proposal by the TTHWP departed from these principles, it was only in relation to substances no longer marketed in either Australia or New Zealand.

The NDPSC was advised that the TTHWP had recently been focusing on harmonisation in respect to Schedule 2 and 3 substances. In cooperation with New Zealand, the Working Party had identified numerous substances which were not registered in either or both Australia or New Zealand. The Working Group had therefore recommended to the NDPSC that these substances should not be deleted from the respective scheduling classification but that the most pragmatic way of dealing with the harmonisation of their scheduling was to place the parent drug in Schedule 4 and delete or amend as appropriate the corresponding Schedule 2 and/or Schedule 3 entries. It was also noted that most of the substances in question were old and had been historically assessed. By including them in Schedule 4, any future application for registration of a medicine containing those substances would necessitate an appropriate application to the registration authority accompanied by contemporary data in-keeping with current standards.

The NDPSC agreed that, given the large volume of harmonisation work yet to be completed, the Working Party’s proposed approach for dealing with those substances no longer marketed presented a strategic solution that maintained the momentum towards

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 28

harmonisation. However, the agreement of NCCTG to proceed in this way would be sought. Substances implicated in this decision and for which there were no S2 or S3 products marketed in Australia and New Zealand included butoconazole, butraconazole,carbuterol, clemastine, clemizole, copaiba balsam, dichlorophen, dimethothiazine, diphenylpyraline, ethyl chloride, flunisolide, hexoprenaline, hydrargaphen, jalap resin, mebhydrolin, mequitazine, pentaerythritol tetranitrate, phenylpropanolamine, phenyltoloxamine, pomegranate and thenyldiamine.

The Committee was advised that New Zealand was also in agreement with this approach for older substances which were no longer marketed.

The Committee also noted proposals from the TTHWP in relation to the harmonisation with New Zealand of scheduling for certain substances for the treatment of tinea pedis viz bifonazole, clotrimazole, econazole, ketoconazole, miconazole, oxiconazole and tioconazole. In New Zealand, products containing these substances for the treatment of tinea pedis are exempt from scheduling. The proposal to achieve scheduling harmonisation was therefore to amend the current Schedule 2 entries in the SUSDP to read “in preparations for dermal use except in medicines for tinea pedis only”. In the case of oxiconazole (for which there are no products for the treatment of tinea pedis registered in Australia), a Schedule 4 entry with exceptions was proposed.

The NDPSC also noted advice from the TTHWP that the scheduling for cimetidine, famotidine, nizatidine and ranitidine was almost “essentially harmonised”. In New Zealand, specific approval by the Minister or Director General was required to supply these substances as an S2 medicine. However, unlike the SUSDP entry, the New Zealand classification was not limited to “gastro-oesophageal reflux”. The scope of the permitted indications was therefore different. To achieve scheduling harmonisation, the TTHWP proposed to the NDPSC that the SUSDP be amended by removing reference to the indication (which was considered a matter for the registration authority), and adding “when sold in the manufacturers original pack containing not more than 14 days’ supply”

The TTHWP had also proposed that, in order to achieve scheduling harmonisation for prilocaine, the NDPSC give consideration to deleting “topical use” and adding “dermal use” in line with the New Zealand classification. However, this would exclude eye drops which are covered by the terms “external use” or “topical use” in association with the descriptor “for ophthalmic use” or “for ocular use” or “in eye drops containing ……”. As there are no eye drop medicines containing prilocaine on the ARTG, it was anticipated that this proposed amendment would not have product implications .

TTHWP had also considered the harmonisation of scheduling for silver sulfadiazine. The Working Party had sought comment from XXXXXXXXX which noted the importance of the use of silver sulfadiazine for the treatment of minor burns. The Working Party’s advice to NDPSC was that in the interests of harmonisation and in the absence of any public health concerns associated with a relaxation of scheduling to harmonise with New Zealand, the scheduling of silver sulfadiazine be aligned with that of New Zealand.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 29

The Committee was also informed that, due to his impending retirement, the June 2005 TTHWP meeting would be the last meeting for XXXXXXXXX and that a suitable replacement would need to be agreed by the jurisdictions. The NDPSC was advised that the States and Territories had agreed that XXXXXXXXX from XXXXXXXXX had agreed to replace XXXXXXXXX on the TTHWP).

The Committee also noted that as there remained considerable work to be done to achieve harmonisation of medicine scheduling with New Zealand, it was essential that the TTHWP continue beyond June 2005 when current funding was expected to cease.

OUTCOME

The Committee agreed that foreshadowing the harmonisation recommendations for consideration at the June 2005 meeting by way of Gazettal would allow any commercial interest in the substances to be identified.

FORESHADOWED DECISION (To be considered at the June 2005 meeting)

Schedule 2 – New entries

MEPYRAMINE in preparations for dermal use.

SILVER SULFADIAZINE for external use in packs containing 50 grams or less.

Schedule 2 - Amendments

BIFONAZOLE – amend entry to read:

BIFONAZOLE in preparations for dermal use except:

(a) in preparations containing 1 percent or less of bifonazole for the treatment of the scalp; or

(b) in preparations for the treatment of tinea pedis.

CLOTRIMAZOLE – amend entry to read:

CLOTRIMAZOLE for human use in dermal preparations except in preparations for the treatment of tinea pedis.

DICHLOROPHEN – delete entry

DIPHENYLPYRALINE – delete entry

ECONAZOLE – amend entry to read:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 30

ECONAZOLE for human use in dermal preparations except in preparations for the treatment of tinea pedis.

FAMOTIDINE – amend entry to read:

FAMOTIDINE when sold in the manufacturer’s original pack containing not more than 14 days supply.

KETOCONAZOLE – amend entry to read:

KETOCONAZOLE in preparations for dermal use except:

(a) in preparations containing 1 percent or less of ketoconazole for the treatment of the scalp; or

(b) in preparations for the treatment of tinea pedis.

MICONAZOLE – amend entry to read:

MICONAZOLE for human use in dermal preparations except in preparations for the treatment of tinea pedis.

NIZATIDINE – amend entry to read:

NIZATIDINE when sold in the manufacturer’s original pack containing not more than 14 days supply.

PRILOCAINE – amend entry to read:

PRILOCAINE in preparations for topical use containing 10 per cent or less of total local anaesthetic substances.

RANITIDINE – amend entry to read:

RANITIDINE when sold in the manufacturer’s original pack containing not more than 14 days supply.

THENYLDIAMINE – delete entry

TIOCONAZOLE – amend entry to read:

TIOCONAZOLE in preparations for dermal use except in preparations for the treatment of tinea pedis.

Schedule 3 – Amendments

CIMETIDINE – amend entry to read:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 31

CIMETIDINE when sold in the manufacturer’s original pack containing not more than 14 days supply.

CLEMASTINE – delete entry

DIPHENYLPYRALINE – delete entry

FLUNISOLIDE – delete entry

MEPYRAMINE – delete entry

PHENYLPROPANOLAMINE – delete entry

PHENYLTOLOXAMINE – delete entry

THENYLDIAMINE – delete entry

Schedule 4 – New entries

BUTOCONAZOLE.

BUTRACONAZOLE.

CARBUTEROL.

COPAIBA BALSAM.

DICHLOROPHEN.

DIMETHOTHIAZINE.

HEXOPRENALINE.

JALAP RESIN.

MEQUITAZINE.

PENTAERYTHRITOL TETRANITRATE.

PUNICA GRANATUM (POMEGRANATE).

Schedule 4 - Amendments

BIFONAZOLE – amend entry to read:

BIFONAZOLE in preparations for dermal use except:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 32

(a) in preparations containing 1 percent or less of bifoconazole for the treatment of the scalp; or

(b) in preparations for the treatment of tinea pedis.

CLEMASTINE – amend entry to read:

CLEMASTINE.

DIPHENYLPYRALINE – amend to read:

DIPHENYLPYRALINE.

ETHYL CHLORIDE – amend entry to read:

ETHYL CHLORIDE.

FLUNISOLIDE – amend entry to read:

FLUNISOLIDE.

HYDRARGAPHEN – amend entry to read:

HYDRARGAPHEN.

KETOCONAZOLE – amend entry to read:

KETOCONAZOLE except:

(a) when included in Schedule 2;

(b) in preparations containing 1 percent or less of ketoconazole for the treatment of the scalp; or

(c) in preparations for the treatment of tinea pedis.

MEPYRAMINE – amend entry to read:

MEPYRAMINE except when in Schedule 2.

OXICONAZOLE – amend entry to read:

OXICONAZOLE except in preparations for dermal use for the treatment of tinea pedis.

PHENYLPROPANOLAMINE – amend entry to read:

PHENYLPROPANOLAMINE.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 33

PHENYLTOLOXAMINE – amend entry to read:

PHENYLTOLOXAMINE.

SILVER SULFADIAZINE – amend entry to read:

SILVER SULFADIAZINE for external use in packs containing more than 50 grams.

THENYLDIAMINE – amend entry to read:

THENYLDIAMINE.

Schedule 6 - Amendments

DICHLOROPHEN – amend entry to read:

DICHLOROPHEN except:

(a) when included in Schedules 4 or 5; or

(b) in fabrics other than when:

(i) for human therapeutic use; or

ii) as part of a registered pesticidal product.

2. PROPOSED CHANGES/ADDITIONS TO PARTS 1 TO 3 AND PART 5 OF THE STANDARD FOR THE UNIFORM SCHEDULING OF DRUGS AND POISONS.

2.2 SUSDP, PART 2

2.2.1 LABELS FOR SCHEDULE 8 SUBSTANCES

PURPOSE

The Committee considered harmonisation of labelling requirements for Schedule 8 substances with the New Zealand Misuse of Drugs Act.

BACKGROUND

Labelling and availability of controlled substances in New Zealand is controlled through the Misuse of Drugs Act (MODA) rather than through the medicine schedules as in Australia.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 34

MODA was considered at the June 2003 meeting of the Trans-Tasman Harmonisation Working Party (TTHWP) where an S8 labelling scheme that met both Australian and New Zealand labelling requirements was endorsed.

The June 2003 NDPSC meeting considered the TTHWP decision and agreed to foreshadow an amendment to the SUSDP which was intended to achieve partial harmonisation in light of legislative differences between the two countries. The amendment would allow the NZ designation, as specified in New Zealand’s MODA, to be included on the label of Schedule 8 medicines in Australia. The Committee also agreed to recommend to the New Zealand Ministry of Health that they vary the labelling requirement for controlled drugs included in Schedule 8 to include the letters “NZ” preceding the designation for the controlled substance.

The foreshadowed amendment was considered at the October 2003 meeting where it was agreed to drop the letters “NZ” as their inclusion could lead to confusion and would not meet the requirements of the MODA.

The October 2004 meeting considered comments received in relation to the foreshadowed amendment and agreed to proceed with the foreshadowed amendment.

DISCUSSION

The Committee noted that in November 2004 the NCCTG considered options for harmonisation of signal headings and the requirements for medicine labelling including:

• amending the scheduling standard to allow the New Zealand designated category for the Misuse of Drugs Act 1975 (MODA) to be included on the signal heading line; • acceptance of dual signal headings; and • changing the MODA to allow for labelling requirements of the joint therapeutic products legislation to take precedence over the MODA (in the case where there are any conflicting requirements). The Committee was advised that in considering these options, NCCTG members noted the following:

• Australia had already made changes to the requirements for the signal heading on scheduled medicines some years ago to align with the New Zealand Medicines Act; • amending the scheduling standard to allow the New Zealand designated category for the MODA to be included on the signal heading line would not resolve the need for different signal headings in Australia and New Zealand for other medicines containing controlled drugs such as benzodiazepines and pseudoephedrine; • options 1 and 2 could be seen as being contrary to the intent of the Australian and New Zealand Treaty to establish a single bi-national agency to regulate therapeutic products; and

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 35

• it is usual practice when making significant changes to legislation to identify consequential changes required to other legislation, such as the MODA. The Committee also noted the following NCCTG policy preferences:

• labels in Australia and New Zealand should be uniform; • New Zealand reconsider amending the MODA (as a consequential amendment to the new trans-Tasman legislation) in order to maximise harmonisation of labels and signal headings for medicines for human use; and • should New Zealand determine that it would be unduly difficult to make the necessary legislative amendments to the MODA within a reasonable timeframe, this matter should be referred to the Therapeutic Products Interim Ministerial Council for consideration. The Committee accepted the NCCTG policy preferences, noting that the foreshadowed amendment could be contrary to the intent of the Treaty.

A member advised the Committee that the labelling of controlled drugs would be raised at the next NCCTG meeting and it was likely that New Zealand would be asked to look at amending the MODA. The Committee endorsed further efforts by New Zealand to address the MODA labelling issues.

The Committee noted that there existed an opportunity for industry to provide input to New Zealand regarding the benefits of a single trans-Tasman medicine label.

The Committee was informed that the consideration of harmonisation of labelling requirements for Schedule 8 substances with the New Zealand MODA was included in the pre-February 2005 meeting gazette notice and no public submissions were received.

OUTCOME

The Committee agreed that the current Schedule 8 signal heading remained appropriate, noting the NCCTG’s recommendation that medicine labels in Australia and New Zealand should be uniform under revised trans-Tasman arrangements for medicines.

2.2.2 CONTAINERS FOR ESSENTIAL OILS

PURPOSE

The Committee considered a proposal to change the packaging requirements for essential oils in Schedule 6.

BACKGROUND

At the May 1999 NDPSC meeting the Committee took an “in principle” decision to allow a general exemption from the requirements of scheduling for containers of essential oils

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 36

having a volume ≤ 15 mL, a restricted flow insert, and labelling which includes “Keep out of reach of children” and “Not to be taken” or other words to that effect. As the scheduling of each oil was considered individually, this decision was considered to be a baseline, with the option of greater or lesser restrictions to be applied as necessary. Some oils have a further cut-off for containers having a volume ≤ 25 mL, a restricted flow insert (RFI), labelling, and a Child-Resistant Closure (CRC) (e.g. Eucalyptus oil, Bay oil). Some oils have a cut-off at 25 mL rather than 15 mL (e.g. Basil oil, Nutmeg oil).

DISCUSSION

The Committee considered correspondence received from XXXXXXXXX requesting an exemption from the use of standard embossed poisons bottles for 50 mL and 100 mL bottles for essential oils scheduled in Schedules 5 and 6, and for the Committee to allow the use of “Gaasch” bottles with RFI and CRC. The Committee examined the following examples of XXXXXXXXX’s current and proposed containers:

• Current 10 mL bottles, with RFI and standard tamper evident cap; • Current 50 mL and 100 mL bottles, in approved embossed poisons bottles with CRC; • Proposed 50 mL and 100 mL “Gaasch” bottles, with RFI, warning label and CRC; and • A 10 mL bottle of Eucalyptus oil, to demonstrate the flow rate of the RFI. The Committee noted that while the proposal related to substances in Schedules 5 and 6, the Gaasch bottles provided by the applicant appear to meet the criteria for Containers of Schedule 5 poisons set out at Part 2 of the SUSDP, sub-paragraph 23 (1) (iii). Therefore, only consideration of those essential oils listed in Schedule 6 was required.

The Committee noted from previous considerations that technical difficulties prevent the use of embossed labels, as it is not possible to raise the text on an adhesive label to the extent required by Australian Standard AS 2216-1997.

The Committee felt that for essential oils, the sample bottles provide an appropriate level of safety. The Committee considered that an amendment for container requirements in part 2 of the SUSDP to allow the use of Gaasch bottles would not represent a risk to public health and safety.

The Committee noted that pre-meeting submissions were received from XXXXXXXXX and XXXXXXXXX. XXXXXXXXX made no specific comments, but reserved the option to respond to any specific issues arising in the post-meeting notifications. XXXXXXXXX advised that it is an interested party and stakeholder and would appreciate being advised of the Committee’s considerations, with the opportunity for further submission, if appropriate.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 37

DECISION 2005/43 – 2

The Committee agreed to amend the SUSDP to allow the use of amber glass containers for Schedule 6 essential oils which do not comply with the tactile identification requirements of the Australian Standard if the container is fitted with a restricted flow insert and a child resistant closure.

Part 2 – Labels and Containers –Amendment

Paragraph 21a – Insert paragraph

21a. Notwithstanding subparagraph 21, a poison which is in Schedule 6 and is an essential oil may be packed in a amber glass container which does not comply with the tactile identification requirements of the Australian Standard if:

(1) the other safety factors are not diminished; and

(2) the container has a restricted flow insert and a child-resistant closure.

AGRICULTURAL/VETERINARY, INDUSTRIAL AND DOMESTIC CHEMICALS

4. OTHER OUTSTANDING MATTERS FROM PREVIOUS MEETINGS

4.1 EYELASH AND EYEBROW TINTING PRODUCTS

PURPOSE

The Committee considered the foreshadowed amendment to Appendix C for phenylenediamines and the foreshadowed inclusion of an entry in Appendix C for toluenediamine to preclude their use in the dying of eyelashes and eyebrows.

BACKGROUND

At the February and June 2004 NDPSC meetings the Committee considered the outcomes of investigations into incorrectly packed and labelled eyelash and eyebrow tinting and hair care products containing paraphenylenediamine and toluenediamine. XXXXXXXXX advised the Committee that XXXXXXXXX had investigated recent claims of the inappropriate retail sale of several hair dye products. These products were not labelled with the appropriate warnings – “This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye”; or as a Schedule 6 poison.

The Committee was also advised that XXXXXXXXX had also taken interest in these products and had informed companies that, until the labelling of eyelash and eyebrow

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 38

tinting products issue was resolved, XXXXXXXXX would only allow salon use of these products. Companies were also warned that, if such products were found on retail sale, action could be taken against a company. It was indicated that for a successful resolution to this issue the Committee would need to assess the potential for eye damage resulting from exposure to eyelash and eyebrow tinting products containing paraphenylenediamine and toluenediamine.

At the October 2004 NDPSC meeting the Committee noted the outcomes of the NICNAS preliminary review of chemicals in hair dyes provided by XXXXXXXXX and the NICNAS report on skin and eye irritancy for paraphenylenediamine and toluenediamine. Based on the outcomes of the NICNAS report on skin and eye irritancy, the Committee agreed to foreshadow an amendment to the current Appendix C entry for phenylenediamines to include the prohibition on use for eyelash and eyebrow tinting. The Committee further agreed to foreshadow the inclusion of a new Appendix C entry for toluenediamines to prohibit its use in eyelash and eyebrow tinting. This action was taken due to concerns surrounding the potential of the chemicals to cause severe eye injuries.

DISCUSSION

The Committee acknowledged public submissions received from XXXXXXXXX and two members of the public.

The XXXXXXXXX submission was referred to NICNAS for assessment. Due to a lack of information on the methodology, NICNAS was unable to critically evaluate the data. Only summaries of the test results were presented in the submission and NICNAS considered that more information regarding the tests carried out was required in order to provide a suitable assessment.

The Committee expressed concern regarding the safety and training material provided by the XXXXXXXXX XXXXXXXXX industry, which was considered inadequate for the purpose of teaching the safe application of eyelash and eyebrow tinting products. XXXXXXXXX agreed to liaise with the XXXXXXXXX XXXXXXXXX industry regarding a compliance awareness-raising campaign as well as appropriate training material, directions for use and warning statements. The Committee also took note of submissions from individuals who preferred to use the products in their homes rather than in salons for economic and personal reasons.

The Members observed that while the compounds in question were clearly sensitisers with the potential to cause a strong allergic response, there was no evidence to suggest that serious adverse effects were common. The Committee was aware of only a few isolated cases, and considered that the matter might be dealt with more appropriately by ensuring adequate labelling. The Committee also expressed concern that inclusion in Appendix C of phenylenediamines and toluenediamine preparations for use in eyelash and eyebrow tinting could result in hair-dyes being inappropriately used for eyelash and eyebrow tinting.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 39

The Committee agreed to foreshadow two options; an amendment to the Schedule 6 entry to allow the use of properly labelled eyelash and eyebrow tinting products in salons only, and that equal consideration would be given to an equivalent amendment which would allow home use of such products. The Committee also agreed to seek expert advice from XXXXXXXXX in relation to the potential for eyelash and eyebrow tinting products containing phenylenediamines and toluenediamines to cause injury to eyes.

OUTCOME

The Committee agreed to foreshadow a proposal to amend the entries for phenylenediamines and toluenediamines in Schedule 6 to allow the use of properly labelled eyebrow and eyelash tinting products containing these substances in the home or salons. Furthermore, the Committee agreed to foreshadow the inclusion in Appendix C of other preparations containing phenylenediamines and toluenediamines for eyebrow and eyelash tinting which would not be covered by the Schedule 6 entry. The Committee agreed to take this approach on the grounds that the potential hazard posed by such products when used in homes or salons could be addressed through appropriate labelling which should also address the potential for hair-dye products to be used inappropriately for eyelash and eyebrow tinting should eyelash and eyebrow tinting products containing phenylenediamine and toluenediamine be placed in Appendix C. Furthermore, members agreed to seek further information about training materials aimed at teaching beauty therapists the safe application of eyelash and eyebrow tinting products, and seek expert advice from XXXXXXXXX.

FORESHADOWED DECISION (For consideration at the June 2005 Meeting)

Option 1 – for salon use only

Schedule 6 –Amendment

PHENYLENEDIAMINES – amend entry to read:

† PHENYLENEDIAMINES and alkylated phenylenediamines not separately specified in these Schedules:

(a) in preparations packed and labelled for photographic purposes;

(b) in preparations packed and labelled for testing water except tablets containing 10 mg or less of diethyl-para- phenylenediamine or dimethyl-para-phenylenediamine in opaque strip packaging provided the directions for use include the statement, “Do not discard testing solutions into the pool”;

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 40

(c) in hair dye preparations except when the immediate container and primary pack are labelled with the following statements:

KEEP OUT OF REACH OF CHILDREN; and

WARNING - This product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye. written in letters not less than 1.5 mm in height; or

(d) in eyelash and eyebrow tinting products except when the immediate container and primary pack are labelled with the following statements:

FOR SALON USE ONLY; and

WARNING - This product contains ingredients which may cause skin irritation to certain individuals, and when used for eyelash and eyebrow tinting may cause injury to the eye. A preliminary test according to the accompanying directions should be made before use.

written in letters not less than 1.5 mm in height.

TOLUENEDIAMINE

(a) in hair dye preparations except when the immediate container and primary pack are labelled with the following statements:

KEEP OUT OF REACH OF CHILDREN; and

WARNING - This product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye. written in letters not less than 1.5 mm in height; or

(b) in eyelash and eyebrow tinting products except when the immediate container and primary pack are labelled with the following statements:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 41

FOR SALON USE ONLY; and

WARNING - This product contains ingredients which may cause skin irritation to certain individuals, and when used for eyelash and eyebrow tinting may cause injury to the eye. A preliminary test according to the accompanying directions should be made before use.

written in letters not less than 1.5 mm in height.

Appendix C –Amendment

PHENYLENEDIAMINES – amend to read:

PHENYLENEDIAMINES in preparations for skin colouration and dyeing of eyelashes or eyebrows except when included in Schedule 6.

Appendix C – New entry

TOLUENEDIAMINE in preparations for skin colouration and dyeing of eyelashes or eyebrows except when included in Schedule 6.

Appendix F, Part 1 – New entry

106. WARNING - This product contains ingredients which may cause skin irritation to certain individuals, and when used for eyelash and eyebrow tinting may cause injury to the eye. A preliminary test according to the accompanying directions should be made before use.

Appendix F, Part 3 – Amendment

Poison Warning Safety Statements Directions

Phenylenediamines – amend entry to read:

Phenylenediamines

(a) in hair dyes 21

(b) in eyebrow and eyelash 106 tinting products

(c) in other preparations 1, 4, 8

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 42

Toluenediamine – amend entry to read:

Toluenediamine

(a) in hair dyes 21

(b) in eyebrow and eyelash 106 tinting products

(c) in other preparations 1, 4, 8

Option 2 – salon and home use

Schedule 6 –Amendment

PHENYLENEDIAMINES – amend entry to read:

† PHENYLENEDIAMINES and alkylated phenylenediamines not separately specified in these Schedules:

(a) in preparations packed and labelled for photographic purposes;

(b) in preparations packed and labelled for testing water except tablets containing 10 mg or less of diethyl-para- phenylenediamine or dimethyl-para-phenylenediamine in opaque strip packaging provided the directions for use include the statement, “Do not discard testing solutions into the pool”;

(c) in hair dye preparations except when the immediate container and primary pack are labelled with the following statements:

KEEP OUT OF REACH OF CHILDREN, and

WARNING - This product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye.

written in letters not less than 1.5 mm in height; or

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 43

(d) in eyelash and eyebrow tinting products except when the immediate container and primary pack are labelled with the following statement:

WARNING - This product contains ingredients which may cause skin irritation to certain individuals, and when used for eyelash and eyebrow tinting may cause injury to the eye. A preliminary test according to the accompanying directions should be made before use.

written in letters not less than 1.5 mm in height.

TOLUENEDIAMINE

(a) in hair dye preparations except when the immediate container and primary pack are labelled with the following statements:

KEEP OUT OF REACH OF CHILDREN, and

WARNING - This product contains ingredients which may cause skin irritation to certain individuals. A preliminary test according to the accompanying directions should be made before use. This product must not be used for dyeing eyelashes or eyebrows; to do so may be injurious to the eye.

written in letters not less than 1.5 mm in height; or

(b) in eyelash and eyebrow tinting products except when the immediate container and primary pack are labelled with the following statement:

WARNING - This product contains ingredients which may cause skin irritation to certain individuals, and when used for eyelash and eyebrow tinting may cause injury to the eye. A preliminary test according to the accompanying directions should be made before use.

written in letters not less than 1.5 mm in height.

Appendix C –Amendment

PHENYLENEDIAMINES – amend to read:

PHENYLENEDIAMINES in preparations for skin colouration and dyeing of eyelashes or eyebrows except when included in Schedule 6.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 44

Appendix C – New entry

TOLUENEDIAMINE in preparations for skin colouration and dyeing of eyelashes or eyebrows except when included in Schedule 6.

Appendix F, Part 1 – New entry:

106. WARNING - This product contains ingredients which may cause skin irritation to certain individuals, and when used for eyelash and eyebrow tinting may cause injury to the eye. A preliminary test according to the accompanying directions should be made before use.

Appendix F, Part 3 – Amendment

Poison Warning Safety Statements Directions

Phenylenediamines – amend entry to read:

Phenylenediamines

(a) in hair dyes 21

(b) in eyebrow and eyelash 106 tinting products

(c) in other preparations…………………… 1, 4, 8

Toluenediamine – amend entry to read:

Toluenediamine

(a) in hair dyes 21

(b) in eyebrow and eyelash 106 tinting products

(c) in other preparations…………………… 1, 4, 8

4.2 PYRAFLUFEN ETHYL

PURPOSE

The Committee considered the scheduling of pyraflufen ethyl.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 45

BACKGROUND

At the October 2004 NDPSC meeting, the Committee considered data submitted by XXXXXXXXX in support of the approval of pyraflufen-ethyl. The new active will be incorporated into a new product for use to control post-emergent broadleaf weeds in crops such as cotton, wheat and barley.

Based on its low toxicological hazard, the OCS recommended that pyraflufen-ethyl be exempt from the requirements of scheduling. However, a member expressed concern that because pyraflufen-ethyl belongs to a class of chemicals that inhibits protoporphyrinogen oxidase, it could have a profound effect on people susceptible to porphyria. Accordingly, it was proposed that an exemption from the requirements of scheduling for pyraflufen- ethyl would be inappropriate.

Members expressed concern that the data presented was deficient in information regarding pyraflufen-ethyl’s potential to precipitate an attack of porphyria including risk reduction measures such as label warning statements used on products marketed overseas. It was the view of the members that there was insufficient information before the Committee for a scheduling decision to be made. The Committee agreed to defer consideration of the scheduling of pyraflufen-ethyl in order to seek more information from the sponsor regarding porphyrin metabolism, including measurements of relevant parameters and comment on the product’s potential to trigger an attack of porphyria.

DISCUSSION

The Committee considered the information provided by XXXXXXXXX to address the concerns raised by the Committee at the October 2004 meeting. The Committee noted that the studies had been completed in the late 1990s and expressed concern that the information had not been provided in the original submission.

An expert member informed the Committee that the data submitted by XXXXXXXXX indicated a clear dose/response relationship between concentration of pyraflufen-ethyl and production of porphyrins in the liver of animals. The data also indicated that there is some evidence of effects on red blood cells. The Committee considered that on the basis of this information, it was not appropriate to have the substance unscheduled and the potential hazard was such that Schedule 5 was considered appropriate. The Committee noted that the expert member was not convinced by the applicant’s arguments as they related to skin concentration of porphyrin rather than concentration in the liver and that it is the hepatic effects which are related to likely adverse consequences.

The Committee observed that, while safety for individuals predisposed to porphyria cannot be proven, the products have a similar use pattern in Japan and the US, with no reported clinical cases of porphyria associated with exposure to this substance. Additionally, there are no particular labelling requirements in other countries. However, it was noted that a case of porphyria would not necessarily be linked to exposure to the

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 46

substance by those investigating an attack. The Committee considered that the toxicological data was sufficient to warrant listing of pyraflufen-ethyl in Schedule 5.

The Committee also considered the experience with similar substances in the past. The decision to include pyraflufen-ethyl in Schedule 5 was judged consistent with the scheduling of fumiclorac-pentyl which has a similar mode of action.

DECISION 2005/43 - 3

The Committee agreed to include pyraflufen-ethyl in Schedule 5 on the basis of the potential hazard of precipitating an attack of porphyria. This decision was based on the information provided by the sponsor who indicated a dose/response relationship between concentration pyraflufen-ethyl and production of porphyrins in the liver of animals, with some evidence of effects on red blood cells.

Schedule 5 – New entry

PYRAFLUFEN-ETHYL.

4.3 SODIUM HYDROXIDE

PURPOSE

The Committee considered the current labelling and packaging requirements for sodium hydroxide when in Schedule 6.

BACKGROUND

At the October 2004 NDPSC meeting the Committee considered two cases of injury from caustic soda products submitted by XXXXXXXXX. These cases led XXXXXXXXX to consider options for improved regulation that might reduce the incidence of injury from use of sodium hydroxide in the domestic setting. XXXXXXXXX requested that the committee consider:

• Reviewing the current labelling and packaging requirements for sodium hydroxide when in Schedule 6; and • That a special case be made for caustic soda for labelling directions. That is the creation of an exception for sodium hydroxide when in Schedule 6 in respect of the exemption from the requirement for the provision of clear and adequate directions for use when not packed or sold for a specific purpose (provided for in clause (1)(m) of Paragraph 7 of Part 2 of the SUSDP). Members noted that Appendix F of the SUSDP requires products containing sodium hydroxide to be labelled with warning statements and safety directions advising the consumer that the substance is corrosive; to avoid contact with the skin or eyes; and that precautions should be taken during use (eye protection and protective gloves). The

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 47

Committee further noted that had these precautions been employed in the 2 cases described, injury may have been avoided or, at least, the severity of the injuries sustained may have been reduced.

Members were of the view that the issues raised at the October 2004 NDPSC meeting were more a matter of compliance with required product labelling rather than the adequacy of the warning statements mandated by the SUSDP for sodium hydroxide. Accordingly, the Committee asked that each State and Territory audit the products containing sodium hydroxide in their jurisdiction and report any inconsistencies or non- compliance with the mandatory labelling requirements to the February 2005 meeting.

Further, members were of the opinion that it would also be beneficial to review current Australian warning statements and product labelling requirements for sodium hydroxide against those in other countries.

DISCUSSION

The Committee considered the results of the audit of sodium hydroxide in the marketplace by jurisdictional members. The audit revealed a number of compliance issues including difficulty in reading the label print on two XXXXXXXXX products, and first aid and safety directions and warning statement deficiencies, also on these products. It was considered that these issues related to compliance rather than scheduling and could be remedied through action by jurisdictional members.

The Committee also considered the review of overseas requirements for sodium hydroxide product labelling. The countries reviewed require similar commentary statements and labels, such as signal words, precautionary measures, first aid statements and statements of hazard. The Committee considered that the review confirms that the Australian labelling and packaging requirements remain appropriate.

XXXXXXXXX agreed to approach XXXXXXXXX in conjunction with XXXXXXXXX regarding compliance with the labelling requirements.

The XXXXXXXXX, XXXXXXXXX and XXXXXXXXX members agreed to discuss broader domestic chemical compliance issues with industry bodies. XXXXXXXXX also agreed to explore the development of a communication strategy towards targeting consumer groups with regard to compliance.

OUTCOME

The Committee agreed that the current labelling and packaging requirements for sodium hydroxide remain appropriate. This is based on the strength of the audit of sodium hydroxide products carried out by the States and Territories and the review of overseas requirements for sodium hydroxide product labelling. This review confirmed that the public health and safety issues raised at the October meeting related to compliance with

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 48

the existing requirements rather than the adequacy of the warning statements mandated by the SUSDP.

4.4 PINE OILS

PURPOSE

The Committee considered the inclusion of a general entry for pine oils derived from Pinus radiata in Schedules 5 and 6.

BACKGROUND

The scheduling of pine oils with regard to use as a herbicide was considered at the February 2004 NDPSC meeting. XXXXXXXXX applied for an extension of use for their home garden product, XXXXXXXXX (containing 680 g/L pine oil), to allow commercial broadacre use. Prior to this meeting, pine oils had been removed from Appendix B at the May 1985 NDPSC meeting due to no data to indicate safety in human use being received by the Committee during its review of essential oils.

Pine oils are refined from the α-pinene fraction of the crude sulfate turpentine extract of Pinus radiata. Once applied to target plants, [rest of sentence deleted].

The February 2005 NDPSC meeting noted that the OCS evaluation report identified the product XXXXXXXXX as a moderate skin irritant and a severe eye irritant and that it would appear to be unsuitable for home garden use. Consequently, the Committee agreed to include pine oil derived from Pinus radiata in Schedule 6 when packed and labelled for use as a herbicide. The entry for pine oils was included in SUSDP 19 Amendment No 1, effective 1 September 2004.

At the October 2004 meeting, XXXXXXXXX submitted new studies on eye irritancy and dermal toxicity in rabbits for the concentrated product (68%) and two ready-to-use premixes (10% and 20%). The sponsor sought reconsideration of the scheduling of pine oils with a view to the Committee setting a cut-off to Schedule 5. Based on the data provided, the Committee agreed to include pine oils at 20 per cent or less in Schedule 5 when packed and labelled for use as a herbicide.

In light of the comments received from industry that pine oils are a common fragrance ingredient in consumer products, the Committee was of the opinion that limiting the schedule entries for pine oils to a specific use may be inappropriate on the basis of its acute oral toxicity and widespread use. Accordingly, Members sought information on other uses of pine oils from APVMA, XXXXXXXXX, and XXXXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX (XXXXXXXXX).

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 49

DISCUSSION

Members noted the advice provided by XXXXXXXXX, which indicated that use of pine oils in the cosmetic and fragrance industry is largely confined to that of a freshness component in fragrances at relatively low levels, well below 5%. Product sizes could range up to 350 millilitress, but with very low levels of pine oils. The Committee also noted the information provided by XXXXXXXXX, who indicated that the content of pine oils in pest control, personal care, cleaners and disinfectant products does not generally exceed 10%.

The Committee acknowledged the information provided for consideration by the APVMA regarding concentration of pine oils in consumer products and the pack sizes of products marketed. The list of products containing pine oils provided showed a number of products that would be included within S6 according to the amendments foreshadowed at the previous meeting. It was noted that there were also products at just above 20% pine oil concentration and it was argued by XXXXXXXXX that, as there was unlikely to be a substantive difference in eye irritancy between these products and products containing 20% pine oils. A 25% cut-off to the S5 entry was suggested as being appropriate. However, the Committee considered that a higher cut-off would not be appropriate due to eye irritancy.

Members noted that the APVMA was unable to determine whether the pine oils in pesticide products were derived from Pinus radiata. Members noted that a number of products registered as containing pine oil had reference to the CAS No. 8002-09-3 which refers to Dwarf pine oil/Yarmor pine oil. The Committee noted that it was difficult to definitively identify the source as bulk-purchase pine oils is generally supplied from a variety of sources, which may or may not include Pinus radiata. On this basis, the Committee considered that it was not appropriate to specify the source species; if other pine oils were not irritating to the eye, further scheduling applications would be considered.

The Committee considered that the use-pattern was the driving feature for scheduling of pine oils; aerosol herbicidal use of an eye irritant such as pine oils was potentially very hazardous. Many of the products on the list provided by APVMA were unlikely to be hazardous on the basis of their use-pattern. Therefore it was considered that at present, only herbicidal use needed to be scheduled.

The Committee noted that the terms of reference for the essential oils working party related to acute LD50 data in the rat, and oils were scheduled on this information, in the context of the use in aromatherapy. The Committee observed that the present use, on a large scale as a herbicide, was not considered by the working party.

Members noted that the related substances fir needle oil (Canadian), fir needle oil (Siberian), and Pinus sylvestris (pine needle) oil were currently in Appendix B, and that each of these oils has an acute oral LD50 value of >5g/kg body weight. A Member informed the Committee that these oils had been exempted from the requirements of

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 50

scheduling on the basis of their low oral toxicity, but other data such as eye irritancy had not been considered. As the Committee lacked this data, it was considered appropriate to remove these entries from Appendix B until such time as further data became available. The Committee noted that this did not represent a scheduling decision per se, but rather an acknowledgement that further scheduling considerations may be necessary in the future.

OUTCOME

The Committee agreed to foreshadow the amendment of the Schedule 5 and Schedule 6 entries to include pine oils when packed and labelled as a herbicide, and to foreshadow the removal of juniper berry oil, fir needle oil (Canadian), fir needle oil (Siberian) and Pinus sylvestris (pine needle) oil from Appendix B. The decision to schedule pine oils as a class was taken due to the skin and eye irritancy of pine oils; and on the grounds that the source of the pine oils often cannot be determined. The decision to remove the other oils from Appendix B was taken on the grounds that the Committee has insufficient information to determine their complete safety profile but experience did not warrant scheduling at this time.

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Schedule 5 – Amendment

PINE OILS – amend entry to read:

PINE OILS in preparations containing 25 per cent or less pine oils when packed and labelled as a herbicide.

Schedule 6 – Amendment

PINE OILS – amend entry to read:

PINE OILS when packed and labelled as a herbicide except when included in Schedule 5.

Appendix B - Amendments

JUNIPER BERRY OIL – delete entry

FIR NEEDLE OIL (Canadian) – delete entry

FIR NEEDLE OIL (Siberian) – delete entry

PINUS SYLVESTRIS (PINE NEEDLE) OIL – delete entry

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 51

6. MATTERS REFERRED BY THE AUSTRALIAN PESTICIDES AND VETERINARY MEDICINES AUTHORITY.

6.1 ALPHA-AMYLASE / BETA-GLUCONASE / CELLULASE / PECTINASE / PHYTASE / FUNGAL PROTEASE / XYLANASE

DECISION 2005/43 - 4

The Committee agreed to exempt α-amylase, β-gluconase, cellulase, pectinase, fungal protease and xylanase from the requirements of scheduling and include these enzymes in Appendix B of the SUSDP. Furthermore, the Committee also confirmed that the current exemption of phytase from the requirements of scheduling remained appropriate. The Committee based its decision on the low toxicity profile of the enzymes listed below when used in feed additives. Furthermore, the Committee was reassured that the concerns raised by members at the meeting should be adequately addressed at the registration level through the requirement of appropriate safety directions on the product label.

Appendix B – New entry

Date Reason Area Substance of for of Entry Listing Use α-AMYLASE derived from Aspergillus Niger February a 2.4 2005 β-GLUCANASE February a 2.4 derived from Aspergillus Niger 2005 CELLULASE derived from Aspergillus Niger February a 2.4 2005 PECTINASE derived from Aspergillus Niger February a 2.4 2005 FUNGAL PROTEASE February a 2.4 derived from Aspergillus Niger 2005 XYLANASE derived from Aspergillus Niger February a 2.4 2005

6.2 FIPRONIL AND 4-[4(ACETYLOXY)PHENYL]-2-BUTANONE (CUE LURE)

DECISION 2005/43 - 5

The Committee agreed that the current scheduling of fipronil remains appropriate. The Committee also agreed to exempt 4-[4-(acetyloxy)phenyl]-2-butanone from the requirements of scheduling based on its low toxicity.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 52

Appendix B – New entry

Date Reason Area Substance of for of Entry Listing Use 4-[4-(ACETYLOXY)PHENYL]-2-BUTANONE February b 1.7 2005

6.3 POTASSIUM PEROXOMONOSULFATE/SILVER/ COPPER/SODIUM PERSULFATE

DECISION 2005/43 – 6

The Committee agreed that the present scheduling status of copper (unscheduled), silver (unscheduled) and potassium peroxomonosulfate (Schedule 6), as present in the proposed product, remained appropriate. The Committee also agreed to amend the entry for sodium persulfate in Schedule 6 to include use in products for the treatment of water for swimming pools and spa baths on the basis of acute toxicity. It was noted that the classification of the proposed product in Schedule 6 was consistent with the overall toxicological profile of the product and its proposed use.

Schedule 6 – Amendment:

SODIUM PERSULFATE – amend to read:

SODIUM PERSULFATE

(a) in hair preparations; or

(b) in products for the treatment of water for swimming pools and spas.

6.4 THIABENDAZOLE

OUTCOME

The Committee agreed to defer consideration to allow data for the two unscheduled 50% thiabendazole fungicides to be obtained and to advise XXXXXXXXX accordingly of the outcome.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 53

6.5 DERACOXIB

DECISION 2005/43 - 7

The Committee agreed to include an entry for deracoxib in Schedule 4 of the SUSDP on the grounds that the condition being treated necessitates appropriate veterinary diagnosis and the safe use of this medicine requires management and monitoring by a veterinary professional.

Schedule 4 – New entry

DERACOXIB.

6.6 FORCHLORFENURON

DECISION 2005/43 - 8

The Committee agreed to exempt forchlorfenuron from the requirements of scheduling on the basis of low toxicity.

Appendix B – New entry

Date Reason Area Substance of for of Entry Listing Use FORCHLORFENURON February a 1.6 2005

7. MATTERS REFERRED BY OFFICE OF CHEMICAL SAFETY (OCS) BRANCH

7.1 GLYCOLIC ACID

PURPOSE

The Committee considered the scheduling of glycolic acid.

BACKGROUND

A recent review of the First Aid Instructions and Safety Directions (FAISD) Handbook by the OCS identified an inconsistency in the scheduling of glycolic acid. The OCS review identified several agricultural products which would be unscheduled as the current Schedule 6 entry for glycolic acid only covers cosmetic use.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 54

Glycolic acid is an alpha-hydroxy organic acid that has been used cosmetically in topical preparations for the treatment of hyperpigmentation and photodamaged skin. Glycolic acid is also used in agricultural products as a disinfectant and pesticide.

Glycolic acid in cosmetic products was considered at the November 1999, May 2000 and August 2000 NDPSC meetings under the NICNAS Priority Existing Chemicals Program. At the August 2000 Meeting an entry for glycolic acid was included in Schedule 6 with an exemption for preparations containing 20 per cent or less of glycolic acid and a pH of 3.5 or greater. Glycolic acid was scheduled on the basis of its corrosive irritation potential when applied to the skin or inadvertent contact with the eyes.

DISCUSSION

The Members noted that the current entry for glycolic acid in Schedule 6 only applies to cosmetic products and that the OCS had recommended that the current entry be modified to include products used in agriculture such as pesticides. Additionally, it was proposed that the current scheduling exemptions could be applied to agricultural products. The Committee agreed, given that there were potential exposure routes in the use of glycolic acid containing agricultural products, an amendment to the Schedule 6 entry for glycolic acid to include its use in agricultural chemicals was appropriate, on the basis of the corrosive irritation potential to the skin and eyes. The Committee also agreed that the current exemptions remain appropriate given the use pattern in agricultural products.

The Committee noted that the OCS FAISD Handbook review found 13 registered products containing glycolic acid. The Members were advised that a recent search of PUBCRIS indicated that there are currently 12 products containing glycolic acid registered with the AVPMA. These products are mainly detergents and sanitisers for the dairy industry. Of these products, there would probably be regulatory impact for 3 products which are currently labelled Schedule 5. There would also be regulatory impact on a buffer and wetting agent currently labelled as unscheduled. There will be no regulatory impact for the 6 products which are already Schedule 6 on the basis of other constituents. There is also likely to be no regulatory impact on the remaining 2 products which have glycolic acid concentrations below the cut-off.

The Committee was advised that the consideration of glycolic acid was included in the pre-February 2005 gazette notice and that no public submissions had been received. XXXXXXXXX expressed the view that the producers and users of some of the products affected by the proposed scheduling amendment may not have made submissions to the February 2005 Meeting because they did not consider routinely these products to be agricultural chemicals. Accordingly, the member requested that the Committee give these stakeholders an opportunity to submit comment on the proposed changes. The Committee agreed that, while the products would be clearly defined as agricultural chemicals under The Agricultural and Veterinary Chemicals Code Act 1994, it was appropriate to allow further opportunity for industry comment by foreshadowing the consideration of the scheduling of glycolic acid at the June 2005 meeting.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 55

OUTCOME

The Committee agreed to foreshadow an amendment to the Schedule 6 entry for glycolic acid to include its use in agricultural chemicals on the basis of glycolic acid’s corrosive irritation potential to the skin and eyes.

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Schedule 6 - Amendment

GLYCOLIC ACID – amend entry to read:

GLYCOLIC ACID (including its salts and esters) in cosmetic products or when packaged and labelled for use as an agricultural chemical except:

(a) in preparations for salon use only which are labelled in accordance with the National Occupational Health and Safety Commission’s National Code of Practice for the Labelling of Workplace Substances [NOHSC:2012 (1994)] or its successors;

(b) in preparations containing 5 per cent or less of glycolic acid; or

(c) in preparations containing 20 per cent or less of glycolic acid with a pH of 3.5 or greater.

9. OTHER MATTERS FOR CONSIDERATION

9.1 CARBAMIDE PEROXIDE

PURPOSE

The Committee considered the scheduling for carbamide peroxide.

BACKGROUND

XXXXXXXXX referred concerns regarding the safety of some tooth whitening products to the NDPSC.

The XXXXXXXXX MSDS indicates that carbamide peroxide is a one-to-one ratio of urea and hydrogen peroxide as indicated. 10% Carbamide peroxide is equivalent to 3.62% hydrogen peroxide. Carbamide peroxide releases oxygen on contact with moist tissues and is used to treat infections of the ear, mouth, skin, and mucous membranes and for softening and removal of ear wax.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 56

The TGA currently does not register tooth whitening products because they are considered to be cosmetic and not therapeutic goods. However, a carbamide peroxide containing product – XXXXXXXXX - is listed on the ARTG as a device. A medicine is also registered on the ARTG for removal of ear wax that contains 6.5% carbamide peroxide. A similar ear wax removal product is listed on the New Zealand SMARTI database that contains 7.15% carbamide peroxide (entry listed under urea hydrogen peroxide).

DISCUSSION

The Committee noted that the XXXXXXXXX submitted the following information for the consideration of members:

• Some tooth whitening products being distributed or sold on the internet contain up to 35% carbamide peroxide. According to XXXXXXXXX, dental therapists in Tasmania are trained to use a maximum of 15% carbamide peroxide and that the use of over 15% strength carbamide peroxide products by non-professionals would be dangerous. • An outlet in XXXXXXXXX has been identified as selling tooth whitening products containing carbamide peroxide at concentrations of 10, 16 and 22%. The Committee noted the opinion of the European Commision’s Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers (SCCNFP) which recommended that the content of hydrogen peroxide in tooth whitening products should not exceed 6 % (present or released) with a 50 mg a day limit. Members also noted that the use of tooth whitening products was not recommended prior to or immediately after dental restoration and that conditions such as pre-existing tissue injury or concurrent use of tobacco and/or alcohol may exacerbate the toxic effects of hydrogen peroxide. The SCCNFP concluded that the proper use of tooth bleaching agents containing 0.1 to 6.0 % hydrogen peroxide (or equivalent for hydrogen peroxide releasing substances) was safe if used under the supervision of a dentist.

The Committee noted that while a Drugdex Drug Evaluation report indicated that 10 % carbamide peroxide was an effective tooth whitener its prolonged use was not recommended until long-term studies had confirmed its safety. The report indicated that soft-tissue and/or gingival sensitivity was very common when using peroxide generating tooth whitening products including carbamide peroxide. Adverse reactions also included the possible overgrowth of opportunistic organisms with prolonged use. It was believed that, once released, the hydrogen peroxide radical was capable of inhibiting pulp enzymes, however, this was yet to be proven.

The Committee was advised that a search of the internet located articles addressing carbamide peroxide safety from the American Dental Association, the American Academy of Pediatric Dentistry (AAPD) and the Australian Dental Association (ADA). The Committee noted that common side effects were tooth sensitivity, enamel damage, tissue irritation and increased marginal leakage of an existing restoration were identified.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 57

The AAPD article also noted that a hydroxyl radical byproduct of carbamide peroxide had been associated with periodontal tissue damage and root resorption. Additionally, the Committee noted the observation of the AAPD that there was only a small amount of published bleaching research using child or adolescent patients. The Committee further noted the American Dental Association’s conclusion that 10 years of clinical data supported both safety and effectiveness of 10 % carbamide peroxide tooth whitening products.

Members were of the view that, despite carbamide peroxide being a source of hydrogen peroxide, industry may not recognise the scheduling ramifications of this and not appropriately label tooth whitening products. A member advised the Committee that the carbamide peroxide tooth whitening products currently on the market, whether produced here or imported, were not likely to be compliant with the current Schedule 5 and Schedule 6 labelling for hydrogen peroxide. On that basis, the member suggested that specific entries in the SUSDP for carbamide peroxide would be appropriate.

Accordingly, the Committee agreed to include specific entries for carbamide peroxide in Schedules 5 and 6 of the SUSDP to mirror those for hydrogen peroxide on the basis of clarity.

A member reminded the Committee that an ear wax removal product containing carbamide peroxide had been identified and that perhaps a corresponding entry in Schedule 2 would be appropriate. However, members agreed that the current carbamide peroxide products for removing ear wax would not require a Schedule 2 entry as the use pattern of these products involved little risk of ocular, oral or internal exposure while noting that any substantially higher strength formulations would be controlled by the proposed Schedule 5 and 6 entries.

A member drew to the Committee’s attention the issue of toothpaste and mouthwash and highlighted the previously mentioned European report’s limit for these products of 0.1% hydrogen peroxide. The Committee agreed that oral hygiene products of this strength were of little risk and did not warrant scheduling. Accordingly, the Committee thought it appropriate to include a cut-off to the entries for carbamide peroxide and hydrogen peroxide to avoid the inadvertent capture of toothpastes and mouthwashes.

OUTCOME

The Committee agreed to foreshadow the inclusion of carbamide peroxide in Schedules 5 and 6 and Appendices E and F of the SUSDP to align it with the current hydrogen peroxide scheduling. Furthermore the Committee agreed to foreshadow an amendment to the hydrogen peroxide entries in Schedule 5 and 6 to include a cut-off for oral hygiene products such as toothpaste and mouthwash.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 58

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Schedule 5 – New entry

CARBAMIDE PEROXIDE in preparations containing 18 per cent or less of carbamide peroxide except:

(a) dental hygiene products for the whitening of teeth, containing 0.3 per cent or less of carbamide peroxide; or

(b) in other preparations containing 9 per cent or less of carbamide peroxide.

Schedule 6 – New entry

CARBAMIDE PEROXIDE except:

(a) when included in Schedule 5;

(b) dental hygiene products for the whitening of teeth, containing 0.3 per cent or less of carbamide peroxide; or

(c) in other preparations containing 9 per cent or less of carbamide peroxide.

Appendix E, Part 2 – New entry

Poison New Standard Statements Carbamide peroxide

(a) more than 9 per cent up to 60 per cent A,G3,E2,S1

(b) more than 60 per cent A,G1,G3,G4,E2,S1

Appendix F, Part 3 – New entry

Poison Warning Safety Statement Directions Carbamide peroxide

(a) more than 9 per cent up to 30 per cent 5 1

(b) more than 30 per cent up to 60 per cent 5 2

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 59

(c) more than 60 per cent 2 2,4

Schedule 5 – Amendment

HYDROGEN PEROXIDE – amend entry to read:

HYDROGEN PEROXIDE (excluding its salts and derivatives):

(a) in hair dye preparations containing 12 per cent or less of hydrogen peroxide except in hair dyes containing 6 per cent or less of hydrogen peroxide; or

(b) in other preparations containing 6 per cent (20 volumes) or less of hydrogen peroxide except:

(i) dental hygiene products for the whitening of teeth, containing 0.1 per cent or less of hydrogen peroxide; or

(ii) in other preparations containing 3 per cent (10 volume) or less of hydrogen peroxide.

Schedule 6 – Amendment

HYDROGEN PEROXIDE – Amend entry to read:

HYDROGEN PEROXIDE (excluding its salts and derivatives) except:

(a) when included in Schedule 5;

(b) in hair dye preparations containing 6 per cent (20 volume) or less of hydrogen peroxide; or

(c) dental hygiene products for the whitening of teeth, containing 0.1 per cent or less of hydrogen peroxide; or

(d) in other preparations containing 3 per cent (10 volume) or less of hydrogen peroxide.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 60

PHARMACEUTICALS

12. MATTERS ARISING FROM THE MINUTES OF THE PREVIOUS MEETING (CONSIDERATION OF POST-MEETING SUBMISSIONS UNDER 42ZCZ)

12.1 ASPIRIN

PURPOSE

The Committee considered a post-meeting submission from XXXXXXXXX to extend the timeframe to implement the revised label statements for non-prescription aspirin products.

BACKGROUND

The June 2004 NDPSC meeting supported the MEC recommendation to revise the aspirin warning statement for Reye’s Syndrome and foreshadowed a decision to amend the SUSDP Schedule 2 (S2) and Appendix F entries for aspirin at the October 2004 NDPSC meeting. The MEC recommendation was based on the Review of Aspirin/Reye’s Syndrome Warning Statement.

The October 2004 NDPSC meeting subsequently agreed to amend the S2 and Appendix F, Part 1 entries for non-prescription aspirin in the SUSDP on the grounds of public health and safety. The amendment was expected to take effect from 1 May 2005.

DISCUSSION

The Committee noted the post-meeting comment received from XXXXXXXXX seeking to extend the implementation timeframe for aspirin product labels by at least six months on the following grounds:

• Sponsors were in the process of finalising labelling for aspirin products to comply with the changes foreshadowed to become effective on 1 May 2005 and which required a changeover from SUSDP Appendix F, Part 1 warning statements 34 or 35 or 36 to the new warning statements 101, 102 and 103. • The requirement to change over to the above-mentioned warning statements would not obviate the inclusion of the warning statement concerning Reye’s Syndrome (warning statement 37). Therefore, all revised labels would still include the warning not to give aspirin “to children or teenagers with chickenpox, influenza or fever”. • The edited extract of the Ratified Minutes of the October 2004 NDPSC meeting for ibuprofen states that the Committee “agreed to review the issue of consistency between the Schedule 2 entries for ibuprofen, aspirin and paracetamol at its February 2005 meeting”.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 61

• The cost of each label change including the required notification to the TGA. • The establishment of the Joint Agency would require further, possible extensive, label changes. The Committee accepted XXXXXXXXX’s contention that delaying implementation of this amendment was not a public health issue as the relevant warning related to Reye’s Syndrome would still be provided to consumers by warning statement 37 which is more restrictive as it refers to teenagers, not just children between 12 and 16 years of age.

DECISION 2005/43 – 9 (Variation to Decision 2004/42-19)

In accordance with subregulation 42ZCZ(3) of the Therapeutic Goods Regulations 1990, the Committee agreed to vary Decision 2004/42-19 and extend the implementation date of the revised Reye’s Syndrome warning statement required for non-prescription medicines containing aspirin to 1 January 2006 and include these amendments in SUSDP 20 Amendment No. 2. Members noted that this extended timeframe should allow Industry adequate time to comply with the new label requirements without compromising public health and safety. Furthermore, the Committee asked that the change in the implementation date in the Appendix F, Part 3 entry for aspirin be reflected in SUSDP 20 to provide clarity to stakeholders and avoid potential confusion.

TO BE INCLUDED IN SUSDP 20 AMENDMENT NO. 2 – Effective 1 January 2006

Schedule 2 – Amendment

ASPIRIN - amend entry to read:

ASPIRIN except:

(a) when included in Schedule 4, 5 or 6;

(b) in individually wrapped powders or sachets of granules each containing 650 mg or less of aspirin as the only therapeutically active constituent other than an effervescent agent:

(i) when enclosed in a primary pack that contains 12 or less such powders or sachets of granules; and

(ii) the primary pack is labelled with warning statements to the following effect:

Don’t use [this product / name of the product]: If you have a stomach ulcer In the last 3 months of pregnancy

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 62

If you are allergic to aspirin or anti-inflammatory medicines;

Unless a doctor has told you to, don’t use [this product / name of the product]: For more than a few days at a time With other medicines containing aspirin or other anti- inflammatory medicines If you have asthma In children under 12 years of age In children 12-16 years of age with or recovering from chicken pox, influenza or fever If you are pregnant;

See a doctor before taking [this product / name of the product] for thinning the blood or for your heart. [Can be omitted in products for inhibition of platelet aggregation.];

(c) in tablets or capsules each containing no other therapeutically active constituent other than an effervescent agent when:

(i) packed in blister or strip packaging or in a container with a child-resistant closure;

(ii) in a primary pack of not more than 25 tablets or capsules, each containing 325 mg or less of aspirin, or in a primary pack of not more than 16 tablets or capsules, each containing 500 mg or less of aspirin; and

(iii) the primary pack is labelled with warning statements to the following effect:

Don’t use [this product / name of the product]: If you have a stomach ulcer In the last 3 months of pregnancy If you are allergic to aspirin or anti-inflammatory medicines;

Unless a doctor has told you to, don’t use [this product / name of the product]: For more than a few days at a time With other medicines containing aspirin or other anti-inflammatory medicines If you have asthma

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 63

In children under 12 years of age In children 12-16 years of age with or recovering from chicken pox, influenza or fever If you are pregnant;

See a doctor before taking [this product / name of the product] for thinning the blood or for your heart. [Can be omitted in products for inhibition of platelet aggregation.]; or

(d) in tablets or capsules each containing no other therapeutically active constituent other than an effervescent agent when:

(i) packed in blister or strip packaging or in a container with a child-resistant closure;

(ii) in a primary pack containing 100 or less tablets or capsules, each containing 100 mg or less of aspirin when packed and labelled for the prevention of cardiovascular disease or for the inhibition of platelet aggregation; and

(iii) the primary pack is labelled with the warning statement to the following effect:

For use under medical supervision only.

Appendix F, Part 1 – Amendment

Warning Statement 102 – amend entry to read:

102. Unless a doctor has told you to, don’t use [this product / name of the product]: For more than a few days at a time With other medicines containing aspirin or other anti-inflammatory medicines If you have asthma In children under 12 years of age In children 12-16 years of age with or recovering from chicken pox, influenza or fever; If you are pregnant.

Appendix F, Part 3 – Amendment

Poison Warning Statements Aspirin – amend entry to read:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 64

Aspirin (a) for inhibition of ...... 36 platelet aggregation...... (b) in sustained release ...... 36 preparations containing 650mg or more of aspirin.

(c) in other preparations……………………101, 102 and 103

TO BE INCLUDED IN SUSDP 20 CONSOLIDATED VERSION FOR CLARITY

Appendix F, Part 1 – Amendment

Warning Statement 102 – amend entry to read:

102. Unless a doctor has told you to, don’t use [this product / name of the product]: For more than a few days at a time With other medicines containing aspirin or other anti-inflammatory medicines If you have asthma In children under 12 years of age If you are pregnant.

(Please note that the statement “In children 12-16 years of age with or recovering from chicken pox, influenza or fever” will be incorporated into WS 102 effective from 1 January 2006.)

Appendix F, Part 3 – Amendment

Poison Warning Statements Aspirin – amend entry to read:

Aspirin (a) for inhibition of ...... 36 platelet aggregation.

(b) in sustained release ...... 36 preparations containing 650mg or more of aspirin.

(c) except as above…………………………101, 102, 103 and 37

(Please note that WS 37 is permitted until 31 December 2005; after this date the revised WS 102 will come into effect.)

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 65

12.2 KETAMINE

PURPOSE

The Committee considered post-meeting comment regarding the decision to reschedule ketamine from Schedule 4 (S4) to S8.

BACKGROUND

Ketamine [2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone] is an arylcycloalkylamine structurally related to phencyclidine (PCP) and cyclohexamine. Ketamine has clinical applications in both human and veterinary medicine and is a rapidly acting, relatively safe parenteral analgesic and anaesthetic agent that has been in clinical use since 1970.

The June 2004 NDPSC meeting was advised that the March 2004 National Working Group on the Diversion of Chemical Precursors (NWG) considered the issue of misuse and diversion of ketamine. At this meeting, the NWG noted that the therapeutic use of ketamine had been increasing from human and veterinary anaesthetic to palliative care analgesic and emergency medicine for use by medical practitioners and dentists. However, the NWG was advised that there was growing evidence of illicit use of ketamine due to its psychotropic effects and that the substance had been found in either its pure form or in combination with other substances such as MDMA [N,N-dimethyl- 3,4-(methylenedioxy)phenylethylamine]. The June 2004 NDPSC meeting was advised that the NWG would be seeking to have ketamine rescheduled to S8 of the SUSDP at the October 2004 meeting due to the problem of diversion of the substance to the illicit drug trade.

At the October 2004 NDPSC meeting the Committee agreed to reschedule ketamine from S4 to S8 on the basis of the available information showing an increasing rate of illicit use and evidence of physical and psychological symptoms of ketamine dependence among recreational users.

DISCUSSION

The Committee considered a post-meeting submission from the XXXXXXXXX. XXXXXXXXX submission opposed the decision and raised the following points for consideration:

• The Copeland and Dillon paper considered at the last meeting did not support the necessity to reschedule. • Law enforcement officials had advised XXXXXXXXX that they did not believe that evaporation of the finished product and grinding of crystals was a significant source of the drug for the illicit market.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 66

• Information provided by wholesalers in the veterinary field did not support the Committee’s statement at the previous meeting that “at times legitimate supplies of ketamine were difficult to obtain due to the level of diversion for unlawful purposes”. • Wholesalers would be forced to go to considerable expense and trouble if ketamine was rescheduled. • Penalties for possession of S4 compared to S8 were not significantly different, and therefore rescheduling would not achieve a deterrent effect. In addition, scheduling is not an effective mechanism for addressing the illicit trade of ketamine and its importation for illicit use. • The Australian Crime Commission (ACC) proposed Commonwealth legislation would create a “possession without lawful excuse” offence and that this should provide a sufficient deterrent. • XXXXXXXXX recommended that the decision to re-schedule be reversed, or deferred, until other stakeholders and agencies were properly consulted and the true nature of the supply chain was further investigated. The Committee noted the following reports from the jurisdictions in relation to abuse or diversion of ketamine:

• In XXXXXXXXX there had been incidents of theft of ketamine from veterinary surgeries, and two from metropolitan hospitals; • In XXXXXXXXX, there had been a recent loss in transit of ketamine vials being transported from XXXXXXXXX to XXXXXXXXX from the manufacturer to the wholesaler. XXXXXXXXX had also been verbally informed by two veterinary wholesalers that they had numerous attempts of persons trying to obtain ketamine by masquerading as veterinary surgeons; • In XXXXXXXXX, there had been drug seizures involving ketamine; and • In XXXXXXXXX, there had been thefts from hospitals and significant quantities of raw material and finished product were also stolen from a manufacturer. Members recalled the research papers presented at the October 2004 Meeting, including ‘Ketamine and Public Health’ [Copeland and Dillon, National Drug and Alcohol Research Centre, University of New South Wales; undated but prepared post-2003] and ‘Pattern of Use and Harms Associated with Non-Medical Ketamine Use’ [Dillon et al., Drug and Alcohol Dependence 69 (2003), p23-28]. The information presented at the October meeting described ketamine as a non-competitive NMDA receptor antagonist with a range of hallucinatory and other psychoactive effects, and indicated that it can induce schizophrenic-like symptoms in healthy adults and schizophrenic patients. This information also indicated that ketamine is being injected by some users and that while these users were not necessarily placing themselves at risk of HIV infections, they may be susceptible to other blood borne viruses such as Hep C, as well as other injecting risks, such as vein damage. The Committee noted the statement in ‘Ketamine and Public Health’ that “ketamine does not appear to currently pose a significant public health risk”

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 67

(emphasis added), but the Committee further noted that this paper indicated a widening of the recreational use of ketamine in the context of nightclubs, dance parties and raves, and stated that this was potentially dangerous due to the rapid onset of the drug and the intensity of the experience as a whole, with users unprepared for the intensity of its effects when first using the drug.

Members noted the following information on illicit use of ketamine in Australia:

• Data obtained in XXXXXXXXX by forensic testing at a recent rave party found that ketamine was present in 26% of the pills tested and usually in combination with MDMA and/or methylamphetamine. Data collected by XXXXXXXXX indicated an upward trend of ketamine use in the jurisdiction since 2000 among regular ecstasy users; • The XXXXXXXXX preliminary findings included data on where ketamine use occurred and 53% of respondents indicated that nightclubs, rave or dance parties were the usual venue; and • The Australian Illicit Drug Report (AIDR) 2001-2002 produced by the ACC submitted to the October 2004 meeting stated that ketamine was difficult to manufacture and that its precursor chemicals were not readily accessible. On this basis, the report concluded that the drug was unlikely to be clandestinely produced and that therefore the majority, if not all, illicit ketamine may have been diverted from legitimate medical or veterinary sources. The report also noted that ketamine had the potential to be both physically and psychologically addictive and that the finished product was ground and the resultant crystals diverted to the illicit drug market. Further advice from XXXXXXXXX also indicated that whilst importers had been found supplying ketamine to fictitious manufacturers and wholesalers, there was also evidence of diversion from the medical and veterinary supply chain. Members noted that XXXXXXXXX had indicated that the “possession without legitimate use” offence is a provision of the Law and Justice, Serious Drug and Other Measures Bill, planned for introduction to the Commonwealth Parliament at its autumn 2005 sitting. The intent of this legislation is to provide an “import and possession without lawful excuse” offence for substances covered by the legislation which it is proposed will include ketamine. The legislation, if passed, was not expected to come into effect for 12 months, and that it would not contain provisions covering illicit supply, sale or manufacture of drugs. The Committee noted that the legislation similarly would not provide a basis for increased storage, recording or reporting requirement, but that inclusion in S8 would. XXXXXXXXX further indicated that it was not opposed to the inclusion of ketamine in S8 and that it considered scheduling an adjunct to Commonwealth legislative control.

The Committee noted that there were significant differences between penalties for possession of trafficable quantities of S4 or S8 substances and that S8 scheduling should result in better control of ketamine through improved record-keeping, storage, transport and reporting of theft or loss.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 68

The Committee noted the sales data on ketamine products provided by vendors which showed a relatively stable trend of ketamine sales over a five-year period. However, the Committee could not extract an estimate of the amount of ketamine diverted based on the information provided.

A member expressed concern that the additional requirements associated with S8 drugs could adversely impact on legitimate users of ketamine, particularly those in veterinary practice. The Committee noted that legitimate veterinary surgeries were already allowed to carry and administer S8 drugs and that if ketamine was rescheduled to S8 it would be handled in the same as other S8 drugs.

DECISION 2005/43 - 10

In accordance with sub-regulation 42ZCZ(3) of the Therapeutic Goods Regulations 1990, the Committee agreed to confirm its initial decision, Decision 2004/42-20, made at the October 2004 meeting to reschedule ketamine from Schedule 4 to Schedule 8 on the basis of its potential for abuse. The Committee noted that the available data showed an increasing rate of illicit use of ketamine in Australia and that there was evidence of physical and psychological symptoms and ketamine dependence among recreational users.

Schedule 4 - Amendment

KETAMINE – delete entry

Schedule 8 - New entry

KETAMINE.

13. OTHER OUTSTANDING MATTERS FROM PREVIOUS MEETINGS

13.1 PSEUDOEPHEDRINE

PURPOSE

The Committee considered the information provided on strategies to counter the problem of diversion of pseudoephedrine.

BACKGROUND

The June 2002 NDPSC meeting agreed to reschedule all OTC single-active immediate release pseudoephedrine preparations from S2 to S3 of the SUSDP on the rationale that pharmacist intervention would help reduce the problem of diversion to the illicit drug trade while maintaining access for legitimate users. The NDPSC had since kept a watching brief of the remaining pseudoephedrine preparations in S2 and had taken the

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 69

opportunity of asking sponsors to indicate their plans for existing and future product lines.

The October 2004 NDPSC meeting considered rescheduling the remaining S2 pseudoephedrine preparations to S3. The NDPSC received numerous submissions on the rescheduling of pseudoephedrine and the ongoing problem of diversion into the illicit drug trade. The NDPSC was mindful of the need to ensure appropriate access for legitimate users of pseudoephedrine products and of the efforts being made by various stakeholders to prevent diversion. However, the NDPSC remained concerned by ongoing reports of what appeared to be an increasing level of diversion of pseudoephedrine products into the illicit drug trade with the increasing detection in a number of States of clandestine laboratories manufacturing methylamphetamine. Additionally, the information provided to the NDPSC indicated that there has been a shift to combination pseudoephedrine products for diversion to the illicit drug trade following the reclassification of single active products to S3.

The October 2004 NDPSC meeting considered the draft final report on a research project funded by XXXXXXXXX at the request of the National Working Group on the Diversion of Chemical Precursors (NWG). The report entitled “XXXXXXXXX” was aimed at determining the extractability of pseudoephedrine from various formulations and the ease at which pseudoephedrine could be converted into methylamphetamine. Members noted that the majority of products in the report, which did not appear to include liquid or slow release preparations, provided reasonable to high yields of methylamphetamine and that the approach of selective rescheduling to S3 of high risk products was unlikely to offer a long term solution to the problem. The report also showed that the type of products targeted for diversion after single-active products were rescheduled to S3 in June 2002 had shifted to combination products. The report therefore concluded that to reduce the risk of the diversion of pseudoephedrine containing products to the illicit drug production market, it would be important to consider the full range of products available on the market and ensure that appropriate restrictions are uniformly applied to all product lines.

The October 2004 NDPSC meeting agreed to take no scheduling action so as to provide additional time for the initiatives implemented by government, industry and pharmacy organisations to take full effect, but resolved to continue monitoring the problem of diversion of pseudoephedrine. The NDPSC indicated that it was willing to consider rescheduling all pseudoephedrine-containing products to S3 or S4 in the future, if the diversion problem remained unresolved. In the interim, the NDPSC recommended that all pharmacy organisations and ASMI should implement specific guidelines and requirements for all community pharmacists to take the necessary precautionary measures to minimise the potential for pharmacies to be targeted as a source of pseudoephedrine for diversion and all jurisdictions should enforce any mandatory requirements for all S2 pseudoephedrine products to be made inaccessible for self-selection by the public. In addition, the NDPSC requested the TGA to facilitate the registration of new products containing phenylephrine as the decongestant as an alternative to pseudoephedrine.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 70

DISCUSSION

Diversion activities

Members noted the following activities currently in place to address the problem of pseudoephedrine diversion to the illicit drug trade:

• Members recalled that the draft recommendations of XXXXXXXXX considered at the October 2004 NDPSC meeting advised that the XXXXXXXXX had agreed that a number of voluntary measures be implemented as an alternative to reclassifying combination pseudoephedrine products to S3. These measures included: (i) Pharmacists are to ensure that “pseudoephedrine plus antihistamine” combination products are to be stored out of reach and out of sight of the public. This would enable pharmacists and pharmacy assistants to refuse requests for pseudoephedrine-based products without feeling threatened.

(ii) Pharmacists are to ensure that “pseudoephedrine plus analgesic” combination products are to be stored out of reach of the public. Police intelligence indicates that this is a ready source of products for illicit use and therefore implementation of these measures would help minimise shoplifting of products and prevent self- selection.

(iii) Pharmacists are to ensure that all staff are aware of the high incidence of the illicit diversion of all solid dose forms of pseudoephedrine. Staff should be advised that if faced with a suspicious sale, they should not put themselves at risk but act discreetly and refer the sale to the Pharmacist in Charge and if possible, continue to report the details of any suspicious sales or requests to the police.

(iv) Pharmacists are to reduce stock holdings of combination products to no more than one week’s supply and should only order products on an “as needs” basis each week. The intent is to minimise the excess stock on the premises in order to reduce the potential for the pharmacy to be targeted as a source of pseudoephedrine-based products. (iv) Product manufacturers and wholesalers are to cease offering incentives to pharmacists to buy more than a week’s supply of pseudoephedrine-based products.

(v) Company sales representatives are to actively support the new storage recommendations when visiting pharmacies

(vii) Products may still be advertised to the general public.

(viii) Liquid products are not affected by these recommendations.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 71

XXXXXXXXX further indicated that should these voluntary measures fail to prevent diversion of pseudoephedrine, it would recommend reclassification of pseudoephedrine-containing combination products to S3 for consideration at XXXXXXXXX.

• In response to the XXXXXXXXX and NDPSC’s recommendations concerning pseudoephedrine-containing products, XXXXXXXXX developed a set of voluntary guidelines for community pharmacists and their staff in order to assist in dealing with requests for pseudoephedrine-based products and to reduce the flow of such products to illegal activities (“Project Pseudo”). A copy of Project Pseudo was provided for the information of NDPSC members. This project included those voluntary guidelines recommended by the XXXXXXXXX as well as the approach that, in a single purchase, the pharmacy should supply to each customer only one pack of the “out of reach and out of sight” range, unless there were compelling circumstances, in which case not more than two packs of any pseudoephedrine-based product may be supplied. In addition, pharmacists should make a record of pseudoephedrine products and the details of the person making the purchase supplied under compelling circumstances. • XXXXXXXXX strategy had also drawn the attention of the NWG. The NWG indicated that it would be considering the specific issue of pseudoephedrine diversion at their May 2005 meeting with a view to forming a proposal for the Committee’s consideration. • XXXXXXXXX has revised its Psuedoephedrine Code to incorporate the XXXXXXXXX recommendations with particular reference to storage conditions and minimal stock holdings. The issue of “no deals” is addressed indirectly due to perceived anti-competitive issues. These revisions have been approved by XXXXXXXXX and will be implemented by signatories without delay. • XXXXXXXXX has developed a pharmacist and pharmacy awareness campaign to be implemented via a kit to be mailed to all pharmacies and a trade advertising campaign to run from April. Elements of the in-store material will assist legitimate consumers understand that their product of choice will still be available although they now must ask staff. • XXXXXXXXX has apparently a similar position to XXXXXXXXX and will be issuing a check list for pharmacists and other measures such as “Pseudo Watch” door stickers. The Committee also noted a New Zealand (NZ) report on the diversion issue which stated that there were 50 products currently available in NZ from which pseudoephedrine could be extracted.

The Committee supported the initiatives that were implemented.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 72

MEC’s Recommendation

The Committee noted a Minute from the MEC highlighting the following deliberations at the 2 December 2004 MEC meeting relating to pseudoephedrine diversion:

• The MEC was concerned that “while pseudoephedrine diversion is a criminal issue, current scheduling means that pharmacists have to deal with the issue with regard to legitimate medicinal products containing pseudoephedrine”. • The MEC had also resolved to recommend in strong terms that the NDPSC reschedule all pseudoephedrine preparations to S3 or S4. Phenylephrine hydrochloride

The Committee noted that the TGA had approved an application by XXXXXXXXX to register XXXXXXXXX containing phenylephrine, as the decongestant in place of pseudoephedrine, on XXXXXXXXX.

Members noted the sponsor’s advice to the April 2004 MEC meeting that it was their intention to market the single entity pseudoephedrine and phenylephrine products concurrently.

Other pre-meeting submissions

The Committee noted that XXXXXXXXX continued to support an S3 classification for all OTC pseudoephedrine products on the basis that selective rescheduling of pseudoephedrine products was likely to redirect the focus of illicit-users to other pseudoephedrine products remaining in S2.

The Committee also noted the copy of XXXXXXXXX policy documents issued in February 2002 including the relevant publications to help the pharmacy profession deal with pseudoephedrine. XXXXXXXXX indicated that the document was being updated and expected to be completed by the end of February 2005.

Scheduling issue

Members recalled the issue of misuse of non-prescription ephedrine tablets in the early 1990s where ephedrine was similarly diverted to the illicit drug trade for the manufacture of amphetamines and that truck drivers had reportedly abused ephedrine for its stimulant effects. Consequently, the Committee decided to reschedule ephedrine to S4. The Committee agreed to revisit the scheduling history of ephedrine at the next meeting. Pseudoephedrine is the dextro-isomer of ephedrine.

A member raised a concern that the current strategies of moving all pseudoephedrine- containing products behind the counter could increase the risk of injury to pharmacists and their staff as well as encourage theft in pharmacies. Moreover, the member questioned the appropriateness of the current availability of pseudoephedrine-containing

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 73

products as non-prescription given the current problem of pseudoephedrine diversion to the illicit drug trade. Some members suggested that the Committee may wish to consider reclassifying pseudoephedrine products to more restrictive Schedules requiring a prescription in the SUSDP. Furthermore, it was also suggested that advice should be sought from the nose and throat specialists associations regarding the place of pseudoephedrine in contemporary medical practice and the potential implications to legitimate consumers should pseudoephedrine be reclassified as a prescription medicine.

A member advised the Committee that XXXXXXXXX would support the rescheduling of all pseudoephedrine products containing 600 mg or less of pseudoephedrine per pack to S3 and stated that the jurisdiction would support the removal of pseudoephedrine from Appendix H of the SUSDP to disallow advertising.

OUTCOME

The Committee reiterated its support of the initiatives put in place by the various organisations but needed measures of their effectiveness. The Committee also indicated that it would consider scheduling as a mechanism to control the diversion problem should it remain unresolved despite the initiatives implemented by various organisations.

The Committee agreed to foreshadow the consideration of the scheduling of all pseudoephedrine products at the June 2005 meeting including the possible inclusion of such products to more restrictive Schedules requiring a prescription, the removal of pseudoephedrine from Appendix H and the variation to the usual implementation date of any resolution.

13.2 ARIPIPRAZOLE

PURPOSE

The Committee considered the inclusion of aripiprazole in Appendix K of the SUSDP.

BACKGROUND

Aripiprazole is an atypical antipsychotic agent indicated for the treatment of schizophrenia. It is believed that its mechanism of action is mediated through a combination of partial agonist activity at dopamine D2 receptors and serotonin 5-HT1A receptors and antagonist activity at serotonin 5HT2A receptors.

The February 2004 NDPSC meeting confirmed its initial decision made at the October 2003 meeting to include aripiprazole in Schedule 4 (S4) of the SUSDP. However, the NDPSC deferred consideration of the proposal to include aripiprazole in Appendix K to the October 2004 meeting as there were conflicting findings from open literature of the sedation potential for aripiprazole. The NDPSC then sought expert advice from XXXXXXXXX on whether the potential for aripiprazole to cause sedation warranted a

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 74

warning statement. To assist the NDPSC in its consideration, comment was also sought from the ADEC on this issue.

The October 2004 NDPSC meeting considered the expert advice received from XXXXXXXXX. While a review of the open literature was not undertaken, the XXXXXXXXX advised that whilst sedation is an adverse effect of aripiprazole, the Product Information (PI) suggests that it is not of such frequency or severity to justify a label warning statement. Members noted that the XXXXXXXXX did not provide advice on the general issue of the potential for atypical antipsychotics, as a class, to cause sedation. The Committee also noted that XXXXXXXXX, the sponsor of aripiprazole, supported the proposal to include aripiprazole in Appendix K of the SUSDP.

Following the October 2004 NDPSC meeting, the NDPSC requested the TGA that specific recommendations concerning the sedation potential of medicines be included in product evaluation reports, the ADEC and MEC minutes, and in the advice of Delegates. This was to ensure consistency in the advice to consumers in relation to the sedation potential of medicines in the Product Information (PI), Consumer Medicine Information (CMI), Appendix K and ultimately, on the label of dispensed medicines.

DISCUSSION

The Committee noted the following points discussed at the October 2004 ADEC meeting in relation to the potential of aripiprazole to cause sedation:

• From the clinical evaluation report some information regarding sedation was evaluated. In comparison to other antipsychotics and to patients on placebo, the somnolence rate for aripiprazole was 11%, risperidone was 14%, haloperidol 20.5% and 8% for placebo. • The NDPSC cited the following published studies on aripiprazole: (i) Potkin et al (Arch Gen Pscyhiatry 2003) reported a four week double-blind study of 404 patients randomised to 20 or 30 mg aripiprazole, placebo or 6 mg risperidone which found adverse events including insomnia. The somnolence, however, occurred mainly during the first week of treatment and the effect did not extend beyond the first week. The paper provided a table which showed the rate of somnolence for placebo at 11%, 4% for aripiprazole at 20 mg/day and 19% for aripiprazole at 30 mg/day against risperidone 14%.

(ii) Keck et al (Am J Psychiatry 2003) was a study of 262 patients with bipolar disorder and involved the use of aripiprazole 30 mg/day versus placebo. The reported instances of somnolence showed that it was more likely to occur during the first week of treatment which tended to resolve within seven days. Somnolence occurred at a rate of 5% in the placebo group and 20% in the aripiprazole group.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 75

(iii) Pigott et al (J Clin Psychiatry 2003) reported the findings of 310 patients with chronic schizophrenia who were treated with aripiprazole 15 mg versus patients given placebo. The most frequently reported adverse event was insomnia whilst the rate of somnolence was 2% for placebo and 3.3% for aripiprazole.

(iv) The ADEC was unable to obtain a copy of the fourth article by Goodnick et al (Expert Opin Pharmacother 2002).

• On the basis of the clinical evaluation report and analysis of the published studies by the NDPSC, the ADEC formed a view that aripiprazole caused less somnolence compared to haloperidol and olanzapine and was about equal to or slightly less in somnolence rate compared to risperidone. The ADEC also noted that aripiprazole was less sedating than quetiapine, which was a relatively sedating antipsychotic drug. • The ADEC recommended to the NDPSC that there was a potential for aripiprazole to cause sedation during the first week of treatment and that the sedative effect would be similar to that of risperidone. The Committee was provided with a summary of the sedation potential of atypical antipsychotics and haloperidol which was based on the information from existing PI documents and listing in Appendix K of the SUSDP. Members noted that the following antipsychotics already listed in Appendix K had sedation potential based on the PI documents: olanzapine (very common ≥ 10%), risperidone (sedation has been reported more frequently in children and adolescents than in adults while in general, sedation is mild and transient) and haloperidol (no frequency stated). A member pointed out that although the summary showed the sedation potential for amisulpride (3%, versus placebo 0% and haloperidol 4%), clozapine (overall incidence about 40%) and quetiapine (very common ≥ 10% usually during the first two weeks of treatment and generally resolves with continued administration), these three atypical antipsychotics were not listed in Appendix K. Members were of the view that amisulpride, clozapine and quetiapine should be considered for inclusion in Appendix K at the next meeting.

OUTCOME

The Committee agreed to foreshadow the inclusion of amisulpride, clozapine and quetiapine in Appendix K of the SUSDP on the basis of the sedation potential of these antipsychotics.

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Appendix K – New entries

Amisulpride Clozapine Quetiapine

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 76

DECISION 2005/43 – 11

The Committee agreed to include aripiprazole in Appendix K of the SUSDP on safety grounds that there was a potential for aripiprazole to cause sedation during the first week of treatment and that the sedative effect would be similar to that of risperidone.

Appendix K - New entry

Aripiprazole

13.3 MELIA AZEDARACH

PURPOSE

The Committee considered the foreshadowed decision to include Melia azedarach in Appendix C of the SUSDP.

BACKGROUND

Melia azedarach, also called Chinaberry or White Cedar (also known in Australia as "white mahogany"), is a member of the Meliaceae family. The fruit and the bark were considered poisonous and there was great variability in the symptoms seen due to genetic variation of the plant. Parts of the plant that are used for medicinal purposes are the bark, fruits, root bark, leaves and flowers.

The February 2002 NDPSC meeting considered the scheduling of Azadirachta indica (neem) and noted that M. azedarach, an adulterant of neem products, may exhibit significant neurotoxicity. Consequently, the June 2002 meeting agreed to foreshadow the inclusion of M. azedarach or its extracts and derivatives in Appendix C of the SUSDP on the grounds of public health and safety. Whilst the Committee recognised the need to restrict the use of M. azedarach, it agreed to seek additional data from stakeholders on issues such as the appropriate cut-off for exemption, long term safety of M. azedarach and the nature of plant extracts in products. This matter had since been considered over several NDPSC meetings but due to inadequate data the June 2003 meeting agreed to defer further consideration to the June 2004 meeting to allow completion of a safety review on M. azedarach being undertaken at that time by the OCM.

The June 2004 NDPSC meeting noted the OCM safety review report on M. azedarach and considered the CMEC’s recommendation that whilst the plant is not suitable for use as an ingredient in Listed medicines the NDPSC should allow continued access to M. azedarach by healthcare practitioners. On this basis, the CMEC recommended that M. azedarach should not be included in Appendix C of the SUSDP. The NDPSC then agreed not to proceed with the foreshadowed inclusion of M. azedarach in Appendix C of the SUSDP but to foreshadow the possible inclusion of M. azedarach in Schedule 7 (S7), based on the plant’s overall toxicity profile and potential for adverse effects on

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 77

reproductive parameters. Whilst it was recognised that there may be grounds for exempting medicines extemporaneously prepared by healthcare practitioners, the NDPSC was unable to extrapolate from the data available to determine a safe level on which to base a cut-off for exemption to accommodate CMEC’s recommendation. To assist the NDPSC in its consideration, the NDPSC had invited CMEC and XXXXXXXXX to propose a cut-off for exemption for extemporaneously prepared medicines by healthcare practitioners and dilute preparations which took into account the overall toxicity of the plant as well as the safety of such preparations in long term use.

The October 2004 NDPSC meeting noted the advice from CMEC that the August 2004 CMEC meeting concurred with the NDPSC’s view that there was inadequate scientific data available on which to base a safe cut-off level to allow the use of M. azedarach as an ingredient in complementary medicines. The NDPSC also noted that there was no response from XXXXXXXXX. In addition, the NDPSC did not support the approach of including botanicals for human use in S7 of the SUSDP as this Schedule attracted controls in the jurisdictions not consistent with those required for human therapeutic substances. Furthermore, members were cognisant of the move towards the new trans- Tasman agency and the need for scheduling entries related to human medicines to meet both Australian and New Zealand requirements. On this basis, the Committee agreed that it was essential to keep all human therapeutic substances within S2, S3 and S4 of the SUSDP. The NDPSC also noted that the inclusion of M. azedarach in S2 to S4 would automatically allow an exemption from scheduling requirements for preparations containing 10 mg/kg or 10 mg/L of M. azedarach for any use, as specified in SUSDP Part 1(2)(i), which would be contradictory to the advice received from CMEC.

Although the NDPSC had attempted to accommodate the CMEC’s recommendation, the move towards the new trans-Tasman agency had posed difficulty in this regard. Consequently, the October 2004 NDPSC meeting decided to foreshadow the inclusion of M. azedarach including its extracts and derivatives in Appendix C of the SUSDP on the grounds of public health and safety. Following the October 2004 NDPSC meeting, the Secretariat wrote to CMEC and XXXXXXXXX to inform them of the NDPSC’s decision.

DISCUSSION

The Committee noted that CMEC and XXXXXXXXX had not responded to the letter sent by the Secretariat following the October 2004 NDPSC meeting inviting them to comment on the NDPSC’s decision to foreshadow the inclusion of M. azedarach in Appendix C. The Committee also noted that there were no pre-meeting submissions received in relation to this matter for this meeting.

Members acknowledged the 20 entries containing M. azedarach currently listed in the ARTG, all products intended for oral consumption. The products contain up to 670 mg dry equivalent of fruit, leaf, seed, and stem bark or root bark per unit dose which are relatively small amounts compared to traditionally recommended doses. The majority of indications relate to claims as a liver tonic, assisting digestion, carbohydrate metaboliser,

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aids blood circulation, relief of menstrual symptoms or cystitis, and improvement of general well-being. One product is indicated for treatment of dry or inflamed skin. The Committee acknowledged that it was difficult to ascertain whether any of these listed products are available on the Australian market. The Committee also noted that the amounts of plant materials in these listed products are quite low in comparison to the doses that are recommended in traditional Chinese or Indian Ayurvedic medicines (dosages range from 4 to 15 g of the dried stem or root bark, and up to 9 g of the dried fruit), and that the indications in the ARTG for these listed products are different to the traditional uses as stated in the OCM’s safety review report on M. azedarach. Some examples of the traditional uses include: the bark are used to remove intestinal worms, the plant is used as a tonic, antipyretic and treatment of leprosy, eczema and the relief of asthmatic attacks, while the bark and leaves are used for itch.

It was highlighted that the minutes of the April 2004 CMEC meeting did not appear to definitively qualify how widespread the use of the plants are in complementary practice, although it was noted that from the minutes that one of the members who was an Ayurvedic expert advised that M. azedarach was not frequently used in Ayurvedic medicine practice. It was also pointed out that M. azedarach did appear in the Pharmacopoeia for the Peoples Republic of China but that did no necessarily reflect its usage by practitioners of traditional Chinese medicines.

In addition, the Committee noted that to date, there are no known reports of adverse reactions potentially attributable to products containing M. azedarach and that the OCM review mentioned that WHO did not have reports either. However, it was highlighted that as the ADRAC data is almost exclusively provided by doctors and pharmacists and that it was only recent that consumer- initiated reporting has occurred, therefore unless there was a high index of suspicion or a very serious reaction, an adverse effect from Melia azedarach may go unreported.

Due to the variable toxicity of M. azedarach, the inadequate scientific data available on which to base a safe cut-off level and the lack of data to support any scheduling decisions, the Committee therefore agreed that an Appendix C listing was appropriate. It was also agreed that additional data would be required to be submitted to support any proposal to revise the Committee’s decision.

A member highlighted a concern on whether affected sponsors of M. azedarach were aware of the foreshadowed decision to include M. azedarach in Appendix C which had been gazetted. The Committee however noted that this item had been on the agenda for a considerable period providing sufficient opportunity for those with interest on M. azedarach to have submitted relevant information to the Committee.

DECISION 2005/43 – 12

On the grounds of public health and safety, the variable toxicity of M. azedarach and the lack of scientific data on which to base a safe cut-off level, the Committee agreed to include M. azedarach in Appendix C of the SUSDP.

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Appendix C - New entry

MELIA AZEDARACH including its extracts and derivatives.

13.4 ROSUVASTATIN

PURPOSE

The Committee considered the inclusion of rosuvastatin in Appendix D of the SUSDP.

BACKGROUND

The June 2004 NDPSC meeting agreed to include the new medicine rosuvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in Schedule 4 (S4) of the SUSDP following the February 2004 ADEC meeting’s recommendation to approve the registration of XXXXXXXXX (rosuvastatin) 10 mg and 20 mg tablets for the treatment of hypercholesterolaemia. The June 2004 NDPSC meeting was also advised that other HMG-CoA reductase inhibitors, also known as statins, in this class carried a Pregnancy Category C in Australia whereas the US FDA classifies these compounds as Pregnancy Category X substances. Consequently, the NDPSC requested that the Secretariat investigate the pregnancy category for all statins in this class and bring the matter to the ADEC’s attention for consideration.

The October 2004 NDPSC meeting noted that the sponsor of rosuvastatin did not wish to comment on the pregnancy category of rosuvastatin but requested to be kept informed. The Committee also noted that the ADEC advice sought in relation to the pregnancy category of the HMG-CoA reductase inhibitors as a class was yet to be received and agreed to defer further consideration to the February 2005 NDPSC meeting.

XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX XXXXXXXXXXXXXXXXXXXXXXXX.

DISCUSSION

The Committee noted the advice received from the ADEC that since it expected that the HMG-CoA reductase inhibitors could have a teratogenic potential, it was agreed that the ADEC categorisation of risk in pregnancy should be tightened from Category “C” to “D”

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and that use during pregnancy should be contraindicated. The Committee also noted the following deliberations made at the December 2004 ADEC meeting:

• The ADEC was of the view that on pharmacological grounds, because HMG-CoA reductase inhibitors can decrease synthesis of cholesterol and possibly other products of cholesterol biosynthesis, it is possible for the statins to cause foetal harm when administered in early pregnancy. Most of the statins are lipophilic and cross the placenta, with the exception of pravastatin, which is hydrophilic. • The ADEC reviewed two publications that referred to post marketing surveillance of the HMG-CoA reductase inhibitors: (i) Edison and Muenke (New Eng J Med 2004;350:1579-1582): The post marketing data from this paper revealed 178 cases of first trimester statin exposure reported to the FDA between 1987-2001 (52 evaluable cases), 20 reports of malformations, including five CNS and five unilateral limb defects (one case had both). All cases involved lipophilic statins which achieve foetoplacental concentrations similar to maternal plasma. It was acknowledged that the data from the case series could not be used to test the hypotheses of teratogenicity and that the findings supported the need for controlled epidemiological studies to evaluate the teratogenic effects of the statins.

(ii) Manson et al (Reproductive Toxicology 1996;10:439-446): This paper examined pregnancy outcome prospectively for 134 women inadvertently exposed to lovastatin or simvastatin. There were nine reports of congenital anomalies (all first trimester exposure) and showed a spectrum of unrelated malformations without consistent pattern. Among the prospectively followed pregnancies with a known outcome, the proportion of normal outcomes was 85%, congenital anomalies 4.0%, spontaneous abortions 8.0%, foetal deaths/stillbirths 1.0%, and miscellaneous adverse outcomes 2.0%.

• Overall, the ADEC agreed that there was enough evidence to suggest that the reported anomalies could be due to maternal toxicity and the effects on the foetus could be morphological rather than pharmacological. The ADEC therefore resolved that since it expected that the HMG–CoA reductase inhibitors could have a teratogenic potential, the ADEC categorisation of risk in pregnancy should be tightened to Category D and use during pregnancy should be contraindicated. Since this is a class effect, the Product Information (PI) documents for all HMG-CoA reductase inhibitors should be modified accordingly. In addition, a brief description of the data presented in the article by Edison and Muenke should be included in the Pregnancy Classification statement in the PI and the data from the publication by Manson et al should also be included in the text of the PI document. The Committee did not support the inclusion of HMG-CoA reductase inhibitors in Appendix D of the SUSDP as this would restrict prescribing to specialist physicians, while in practice treatment with HMG-CoA reductase inhibitors may be initiated by either a general practitioner or a specialist physician and on-going treatment was often

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under the supervision of a general practitioner. Members also noted that an Appendix D listing would attract additional controls in the jurisdictions that could potentially impose difficulties in accessing the medication particularly in remote areas where there were limited numbers of specialists. In addition, members noted that the inclusion of a substance in Appendix D was traditionally based on the grounds that the substance carried an ADEC pregnancy categorisation of Category X which was defined as a substance having such a high risk of causing permanent damage to the foetus that the substance should not be used in pregnancy or when there is a possibility of pregnancy.

OUTCOME

The Committee agreed that there was no need to include rosuvastatin and the other HMG-CoA reductase inhibitors in Appendix D of the SUSDP at this time. Members were of the view that the medical condition that these medicines are indicated for and the potential contraindications could be appropriately managed and monitored by a general practitioner.

13.6 ZINC COMPOUNDS

PURPOSE

The Committee considered the cut-off for unscheduled preparations containing zinc compounds for human internal use.

BACKGROUND

The June 2004 NDPSC Meeting was advised that a GP in New Zealand (NZ) with interest in nutrition drew XXXXXXXXX’s attention to the Age-Related Eye Disease Study (AREDS) sponsored by the US National Eye Institute. The AREDS study suggested that high-doses of antioxidants and zinc supplementation could slow and in some cases retard the progression of age-related macular degeneration (ARMD). The GP sought advice on whether there were any plans by regulatory authorities to accommodate products containing up to 80 mg elemental zinc in unscheduled dietary supplements. The Committee agreed to consider the scheduling of zinc at the October 2004 meeting. In addition, a member suggested that the issue of correlation between high-level zinc supplementation and copper intake should also be considered.

The October 2004 Meeting considered the AREDS study in detail and noted the risk assessment for zinc undertaken by the UK Expert Group on Vitamin and Minerals. Furthermore, the issue of a possible correlation between high-level zinc supplementation and reduced copper uptake was again raised. The Committee agreed to defer further consideration of the matter to seek advice from XXXXXXXXX and XXXXXXXXX. Specifically, comment was sought on the implications of increasing the allowable daily intake of zinc for general sales to levels identified as having a beneficial effect in the AREDS study (80 mg zinc).

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The October 2004 meeting was also advised by XXXXXXXXX that Australia had assisted in the preparation of the International Programme on Chemical Safety (IPCS) monograph for zinc [WHO 2001 – IPCS Environmental Health Criteria 221:Zinc (extract on human use)] and that this document may be useful when considering the matter at the February 2005 Meeting. The monograph discusses the effects of zinc toxicity on humans.

Zinc compounds are currently Schedule 4 substances for human internal use except when the daily dose limit is 25 mg or less (or up to 50 mg zinc when products comply with labelling warning requirements that the product may be dangerous if taken in large amounts or for a long period). This scheduling was the result of several considerations between August 1986 and November 1988 meetings which was prompted by companies seeking to register zinc products containing up to 1 g of zinc salts per dosage unit. The Committee agreed at the time that there was a potential problem with chronic ingestion of high dose zinc preparations, noting that there was documented evidence of copper depletion associated with zinc therapy. The daily dose limit for unscheduled products in NZ is 20 mg/day.

DISCUSSION

The Committee noted that advice had been received from XXXXXXXXX but not from XXXXXXXXX. XXXXXXXXX’s submission on the issue of increasing the allowable intake of zinc for general sales based on the findings of the AREDS highlighted following points:

• Visual loss from Age-Related Macular Degeneration (ARMD) remains the commonest cause of irreversible blindness in our community and that therefore it is not surprising that data from AREDS has been so well received by eye health professionals desperate to help their patients prevent visual loss. However, careful reading of the AREDS data and consideration of the possible side effects of these supplements should temper this overwhelming enthusiasm. • If the AREDS results are taken at face value, there is no evidence to support the use of such high dose supplementation for subjects in Categories 1 and 2. The authors of the AREDS papers themselves are at pains to emphasize that such supplements are not recommended in these cases. Closer reading of the AREDS results for Category 3; those with either non-foveal geographic atrophy (GA), many intermediate drusen or one large drusen, or Category 4; those with one eye with advanced ARMD also reveals that the effect of high dose supplementation on visual acuity and ARMD progression is not as compelling as initially reported. The major outcome reported in the AREDS papers was a significant reduction in the development of visual loss in subjects in categories 3 and 4, with an odds ratio (OR) of 0.73 [Confidence interval (CI) 0.54-0.00]. This OR, however, was unadjusted for age, sex and smoking, despite being recognised risk factors in the progression of ARMD. Adjusted OR data for the group of patients were not statistically significant (OR 0.75, CI 0.55-1.02).

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• Even if these unadjusted OR are taken at face value, the numbers of patients involved in determining the critical outcomes was outstandingly small. Although 4757 patients were recruited for this study, patients in Categories 1 and 2 (2180 subjects) were excluded due to the lack of progression, and 665 patients were lost to follow up. Approximately 1900 patients remained in the analyses in Categories 3 and 4, with only subjects in Category 4 having an unadjusted OR that was statistically significant. Category 4 had 928 subjects remaining, who were divided into approximately 4 equal treatment groups of 232. Using the unadjusted Ors (the only ones that were reported to be “statistically significant”), 28% in the control group had progression of ARMD (64 subjects) compared to 20% in the combined treatment group (46 subjects), a difference of only 20 patients. The numbers are even smaller when looking at visual loss, 67 subjects in the control group lost >15 letters (29% of 232) in comparison to 53 subjects in the combined treatment group (23% of 232), a difference of only 14 patients. Thus, from 4757 recruits, the crucial finding are based on the outcome from this very small subgroup. Even if we accept the AREDS findings that high dose dietary supplementation is beneficial in Category 3 and 4 subjects, we must also consider the potential side effects of treatment. • The AREDS study found that the risk of GA appeared to be increased, although not statistically significant, in the treatment group. It may therefore be prudent not to recommend the supplement those patients showing the first signs of GA. Furthermore, it is well known that the AREDS formulation should not be given to smokers, as large Scandinavian studies have found that beta-carotene increases the risk by 4 of developing lung cancer. In the AREDS, smokers were either withdrawn or given a preparation without beta-carotene. No data is available as to whether this altered preparation was effective. Thus preparations excluding beta-carotene can not be presumed to have the same effect as those with beta-carotene. In Australia, “Macu-Vision” is such a preparation. • Increased hospitalisations were also noted in the treatment groups, particularly for complications including renal stones, gastrointestinal upset and genitourinary infections. Anaemia also occurred despite the addition of copper to counteract the binding of supplemental zinc to iron in the haemoglobin. Patients taking any supplements containing zinc should be warned of this complication as should their General Practitioners. • Vitamin E supplementation has been implicated in reducing the protective effect of statins in patients at risk of cardiovascular disease. There may also be some reason to be concerned about the long term, high supplementation of zinc and the development of Alzheimer’s disease. High dose zinc supplementation has also been found to elevate the glycosylated haemoglobin in patients with Type I diabetes mellitus and increase blood sugar levels in patients with Type II diabetes mellitus. • Whilst there is great need to provide treatment to people with early ARMD to reduce their risk of severe vision loss, it is important to remember that once such a treatment is recommended, patients could remain on it for decades. Therefore, it is the responsibility of the ophthalmologist to be aware of the basis of their treatment and

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the possible adverse consequences prior to recommending it everyone with drusen. Furthermore, young men and women should not be on long-term therapy of high dose zinc without good data on the risk/benefits to support this approach and the data from the AREDS was limited older groups. The Committee recalled that the UK Expert Group on Vitamins and Minerals noted in its May 2003 report that it was difficult to draw conclusions from the Age-Related Eye Disease Research Group, 2002, with regard to zinc supplementation as only 20% of participants were followed up for the full five years and that no group received zinc alone. The Committee also recalled the following points raised in the UK Expert Group’s risk assessment of zinc toxicity based on review of important studies identified in the May 2003 report:

• In humans, the acute toxic effects of zinc occur at doses of approximately 200 mg or more. Zinc affects iron and copper uptake at supplemental doses of 50 mg/day and above. However, this was not apparent in all studies. The key endpoint was the reduction of copper absorption by zinc. Where the contribution of dietary zinc was also assessed, the lowest level at which effects were apparent (reduced activity of the copper-dependent enzyme ESOD being the most sensitive) was approximately 58-62 mg/day (50 mg supplements plus approximately 8-12 mg/day from food). Reproductive toxicity in rats has been observed at doses above 200 mg/kg bw/day. • Iron and zinc in the diet each affect the gastrointestinal absorption of the other. Few data are available, but high levels of iron are known to interfere with zinc uptake, and more limited data suggest that the reverse interaction also occurs, This has not been considered in detail. • Taking the LOAEL as 50 mg/day and by applying an uncertainty factor of 2 to account for LOAEL to NOAEL extrapolation, a Safe Upper Level of 50/2 = 25 mg/day for supplemental zinc was derived (equivalent to 0.42 mg/kg bw/day in a 60 kg adult). An uncertainty factor of 2 was used, rather than 3, since the effect concerned was a small and inconsistent change in a biochemical parameter. No uncertainty factor was needed for inter-individual variability because this safe upper level was supported by a large number of human studies. Assuming a maximum intake of 17 mg/day from food, a total intake of 42 mg/day (equivalent to 0.7 mg/kg bw/day in a 60 kg adult) was not expected to result in any adverse effects. • Two vulnerable groups were identified: diabetics and sufferers of haemochromatosis. The Committee noted that these vulnerable groups are reasonably common in the general community. The Committee also noted comment from XXXXXXXXX which recommended that the current scheduling provisions in relation to zinc remain on the following grounds:

• For most purposes, zinc should not be taken at no greater than the recommended safe upper levels of zinc. The upper safety limit for zinc intake determined by the Hazard Classifications varies from 25 – 40 mg daily. Currently, preparations with more than 25 mg and less than 50 mg of zinc carry a warning statement about the dangers of

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large amounts for long periods. Furthermore, the NOAEL / LOAEL had been determined at between 50-60 mg of zinc. • The AREDS emphasizes that the zinc formulations were neither a cure for ARMD nor restore any previously lost vision. The combination only helped those considered to have high risk for ARMD to maintain their vision. • The generalisability of the AREDS findings to other populations with different nutritional status was not known and that further large well-conducted randomized controlled trials in other populations are required. • The necessary professional and medical management, monitoring and diagnosis of ARMD and the appropriate treatment of this and other conditions requiring high levels of zinc supplementation would only occur if doses of zinc above 50 mg were regulated at an Schedule 4 level. The Committee noted the following points in the IPCS monograph for zinc:

• In case studies, effects associated with long-term high intakes of zinc (ranging from 150 mg/day to 1 – 2 g/day) had included sideroblastic anaemia, hypochromic microcytic anaemia, leukopenia, lymphadenopathy, neutropaenia, hypocupraemia and hypoferraemia. These effects were reversible upon cessation of zinc therapy and/or repletion of copper status, which were largely attributed to zinc-induced copper depletion. • Zinc supplements should not contain zinc levels that exceed dietary reference values (which range from 5.5 to 13.3 mg/day depending on age, sex or if taken during pregnancy), and should contain sufficient amounts of copper to ensure a ratio of zinc to copper of approximately 7, as is found in human milk. The Committee noted that an ARTG search revealed that there are currently no oral zinc products containing more than 50 mg zinc available in Australia. However, the Committee were advised of the availability of the products in Australia claiming to be formulations based on the AREDS research e.g. XXXXXXXXX and XXXXXXXXX.

The Committee concluded that the available data reviewed supported the safety of long term zinc supplementation at 25 mg per daily dose level and that the current label requirement (not be taken in large amounts or for a long period) for preparations containing 25- 50 mg zinc per daily dose should ensure the safe use of such products.

OUTCOME

The Committee agreed that the current scheduling of zinc remained appropriate based on the available information. Furthermore, on the basis of the uncertainty surrounding the long-term safety of zinc supplementation above 50 mg per day, the Committee reconfirmed its view that professional medical advice should be sought before commencing such a therapy and that products with a recommended daily dose of >50mg zinc remained appropriate as prescription only medicine.

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13.7 2,5-DIMETHOXY-4-ETHYLTHIOPHENETHYLAMINE (2C-T-2) / 2,5-DIMETHOXY-4-IODOPHENETHYLAMINE (2C-I) / 2,5- DIMETHOXY-4-(N)-PROPYLTHIOPHENETHYLAMINE (2C-T-7) / 5-METHOXY-A-METHYLTRYPTAMINE (5-MEO-AMT)

PURPOSE

The Committee considered the foreshadowed decision to include 2,5-dimethoxy-4- ethylthiophenethylamine (2C-T-2), 2,5-dimethoxy-4-iodophenethylamine (2C-I), 2,5- dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7) and 5-methoxy-α- methyltryptamine (5-MeO-AMT) in Schedule 9 of the SUSDP.

BACKGROUND

The October 2004 NDPSC Meeting considered a proposal by XXXXXXXXX to include two substances, 2C-I and 5-MeO-AMT, in Schedule 9 of the SUSDP on the basis of their potential for misuse. It was noted that the European Union had decided to impose control measures and criminal penalties in respect of other phenethylamine analogues such as 2C-T-2 and 2C-T-7. Based on the available information, the Committee formed a view that there was sufficient evidence to suggest that these substances were the subject of abuse and agreed to foreshadow the inclusion of entries for 2C-T-2, 2C-I, 2C-T-7 and 5- MeO-AMT in Schedule 9. While 2C-T-2, 2C-I, 2C-T-7 (but not 5-MeO-AMT) are covered by the class entry for alkoxyphenylethylamines in Schedule 9 by virtue of Part 1, paragraph 2 (c) of the SUSDP, the Committee considered that an individual entry for these substances provided clarity of interpretation for law enforcement agencies and others.

Members noted that deferring formal consideration of this matter to the February 2005 meeting should allow sufficient time to fully investigate the industrial applications of these substances and facilitate consultation with XXXXXXXXX prior to the foreshadowed decision being considered at the February 2005 NDPSC meeting.

DISCUSSION

The Committee noted the advice from XXXXXXXXX that it had not received any information to indicate that 2C-T-2, 2C-I, 2C-T-7 or 5-MeO-AMT were being used for industrial purposes by its members.

Members noted the section of the Model Criminal Code containing a list of controlled drugs and the Code’s definition for determining substances “related to” any of the listed controlled drugs. The Committee noted that 2C-T-2, 2C-I, 2C-T-7 or 5-MeO-AMT are already included in Queensland’s Drugs of Misuse act, and considered that scheduling in S9 would be consistent with controlling the substances from the public health and safety position.

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The Committee noted that the European decision to impose control measures on 2C-I, 2C-T-2 and 2C-T-7 was based on risk assessments carried out by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). The Scientific Committee of the EMCDDA recommended that 2C-I, 2C-T-2 and 2C-T-7 should be controlled substances due to the indication for hallucinogenic/stimulant properties and potential of serious risk to health, these compounds should be controlled substances. 5-MeO-AMT is not presently controlled in the European Union.

Members noted that 2C-T-7 was associated with three deaths in the USA and was temporarily placed into Schedule I of the USA Federal Controlled Substances Act (CSA) on September 20, 2002. On March 18, 2004, the placement was made permanent. 2C-I, 2C-T-2 and 5-MeO-AMT are not specifically listed in the CSA, but are regulated by the USA Drug Enforcement Agency. As analogues of controlled substances, individuals trafficking in these substances may be prosecuted under the CSA.

The scheduling consideration of 2C-I, 2C-T-2, 2C-T-7 and 5-MeO-AMT was included in the pre-February 2005 meeting gazette notice and no public submissions were received.

DECISION 2005/43 – 13

The Committee agreed to individually list 2,5-dimethoxy-4-ethylthiophenethylamine, 2,5-dimethoxy-4-iodophenethylamine, 2,5-dimethoxy-4-(n)-propylthiophenethyl-amine in Schedule 9 of the SUSDP and to include 5-methoxy-α-methyltryptamine in Schedule 9 of the SUSDP.

The Committee took this decision based on the potential for misuse or abuse of these substances and the need for clarity of interpretation for these substances in Schedule 9.

Schedule 9 – New entries

2,5-DIMETHOXY-4-ETHYLTHIOPHENETHYLAMINE *(2C-T-2).

2,5-DIMETHOXY-4-IODOPHENETHYLAMINE *(2C-I).

2,5-DIMETHOXY-4-(N)-PROPYLTHIOPHENETHYLAMINE *(2C-T-7).

5-METHOXY-α-METHYLTRYPTAMINE *(5-MeO-AMT).

13.8 IBUPROFEN

PURPOSE

The Committee considered a proposal to amend the warning statements in the Schedule 2 (S2) entry for ibuprofen for consistency with the S2 aspirin and paracetamol entries in relation to the expiry provisions for old warning statements.

BACKGROUND

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The June 2003 NDPSC meeting agreed to exempt from scheduling divided preparations containing 200 mg or less of ibuprofen per dosage unit in packs containing 25 or less dosage units, when labelled with prescribed warning statements with a recommended maximum daily dose of 1200 mg of ibuprofen. Following consideration of post-meeting comments, the October 2003 NDPSC meeting varied its June 2003 decision and amended the mandatory warning statements required for exempt ibuprofen. The Committee also simplified certain warning statements and included those relating to gastrointestinal complications, pregnancy, asthma and use in certain age groups, to reduce the risk in sensitive sub-populations.

The June 2004 NDPSC meeting received advice from the OTC Medicines Section that the warning statements in relation to long term or excessive use of ibuprofen without medical supervision required under (b)(iv) of the current S2 entry was also duplicated under (b)(v). However, the NDPSC did not take this advice into account in the amendment to the S2 entry for ibuprofen gazetted following the June 2004 meeting as it was the intention of the Committee to make both the old and new warning statements listed under sections (b)(iv) and (b)(v) of the S2 entry for ibuprofen mandatory and that the new warning statements listed under (b)(v) were strengthened to address concerns raised during the public consultation process. The Committee instead agreed to editorially amend the S2 entry for ibuprofen to include an ‘or’ after the first warning statement under part (b)(iv) and replace ‘aspirin’ with ‘ibuprofen’ in the warning statement “…with other medicines containing aspirin or…” under (b)(v).

The October 2004 NDPSC meeting considered a proposal from XXXXXXXXX to amend editorially the duplicated warning statements required for unscheduled ibuprofen preparations specified in S2. In addition, XXXXXXXXX also sought that the implementation date for such warning statements under (b)(v) (the new warning statements) of the S2 entry be the same as that for aspirin and paracetamol and OTC scheduled ibuprofen products, i.e. mandatory from 1 May 2005, for consistency and to avoid confusion. However, members confirmed the outcome of the June 2004 meeting that the current S2 entry for ibuprofen remained appropriate including the mandatory label requirements for exempt products but agreed to review the issue of consistency between the S2 entries for ibuprofen, aspirin and paracetamol at the February 2005 meeting.

DISCUSSION

Duplication of warning against prolonged use for exempt ibuprofen preparations and the inconsistency of the date of effect

The Committee noted that the new warning statements (WS) which includes the warning against prolonged use required on the label of OTC and unscheduled aspirin and paracetamol products would come into effect on 1 May 2005, as agreed at the June 2003 NDPSC meeting. In contrast, the new WS for exempt ibuprofen preparations including

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the warning against prolonged use came into effect on 1 January 2004 but the corresponding new WS for scheduled ibuprofen carried the same date of effect as the non-prescription paracetamol and aspirin preparations, i.e. 1 May 2005, which members considered could be confusing to the industry and to consumers.

Some members expressed a similar concern as that raised in pre-meeting submissions with regard to the difficulty in accommodating all the label warnings on the primary pack without compromising one’s ability to read the labels due to the significantly reduced font size.

The Committee noted the proposal that the duplicated warning against prolonged use required for exempt ibuprofen preparations specified under (b)(iv) of the S2 entry should be deleted and that the date of effect of this change amendment be made the same as that for non-prescription aspirin and paracetamol and scheduled ibuprofen preparations, i.e. 1 May 2005.

The Committee agreed to remove the WS for exempt ibuprofen in (b)(iv) in the S2 entry to remove duplication of warning statements and maintain consistency between the entries for scheduled and exempt ibuprofen, aspirin and paracetamol. Members also noted that this amendment would be included in SUSDP 20 Amendment No. 1 which was expected to take effect on 1 September 2005.

Warning Statements (WS) for NSAIDs recommended by the MEC

Following the June 2004 NDPSC meeting, the Secretariat requested the MEC to review the SUSDP Appendix F, Parts 1 and 3 WS required for all non-steroidal anti- inflammatory drugs (NSAIDs) based on the following issues highlighted by the NDPSC:

(i) WS 101 did not warn against use in patients with a past history of stomach ulcer, and

(ii) WS 102 & 104 did not warn against use in elderly patients most at risk of GI complications from use of NSAIDs, ie. ≥ 60 years old, and did not list medicines commonly taken by consumers on a regular basis which could interact with NSAIDS, eg. antihypertensives and diuretics.

Members noted the following recommendations from MEC which were considered at the August and December 2004 MEC meetings in response to the Committee’s request:

• In relation to the warning against use in patients with a past history of stomach ulcer, the MEC had sought advice from XXXXXXXXX. XXXXXXXXX subsequently requested XXXXXXXXX of XXXXXXXXX for advice on this issue.

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The NDPSC also noted the advice provided to MEC by XXXXXXXXX (a copy of which was also provided to the NDPSC) that the labels of NSAIDs should include advice consistent with the following recommendations:

- Do not use this product if you have a stomach ulcer; - If you have had an ulcer in the past check with your doctor before using this medicine; - Many people carry a stomach germ called Helicobacter pylori. Use of this product in this situation increases the risk of stomach ulcers and bleeding from the stomach even in those who have never had symptoms before. Discuss this with your doctor. - In the absence of this stomach germ, this medicine still increases the risk of ulcers, bleeding from ulcers and bleeding from the intestines. This may occur suddenly or slowly. - This medicine is associated with an increased chance of indigestion or dyspepsia. This often occurs in the absence of an ulcer. If this persists, see your doctor.

Based on the advice provided by XXXXXXXXX, the MEC recommended to the NDPSC that the reference to people with a past history of stomach ulcer should be included in Appendix F, Part 1 WS 101 and in the corresponding WS in the S2 entries for exempt aspirin and ibuprofen. Members also noted that the MEC was of the opinion that the other issues raised by XXXXXXXXX did not warrant inclusion on the product labels at this stage and recommended that the TGA and the MEC should keep a watching brief on ibuprofen and other oral OTC NSAIDs with respect to the other issues raised by XXXXXXXXX.

• WS 104 should be expanded to include the warning “Unless a doctor has told you to, don’t use …If you are aged 65 years or over” for consistency with the warning for unscheduled oral ibuprofen products. • WS 102 and 104 and the corresponding statements for unscheduled oral ibuprofen and aspirin “Unless a doctor has told you to, don’t use [this product / name of product]:” should include an additional point: “If you have impaired kidney function or heart failure”. The MEC had agreed that this statement should advise seeking a doctor before use (as in WS 102 and 104) instead of “Don’t use” (as in WS 101). • WS 104 should be expanded to “With other medicines containing (name of substance), aspirin or other anti-inflammatory medicines or with other medicines that you are taking regularly” as some consumers were unaware that aspirin is an anti- inflammatory medicine and that the existing SUSDP requirement for unscheduled ibuprofen included the WS “or other medicines that you are taking regularly”. The latter was also consistent with the guideline on ibuprofen included in Chapter 9 of the Australian Regulatory Guidelines for OTC Medicines (ARGOM).

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• WS 102 should be expanded to “With other medicines containing aspirin or other anti-inflammatory medicines or with other medicines that you are taking regularly” for consistency with the recommendation for WS 104. • WS 101 and 104 should apply to scheduled oral OTC products containing diclofenac to maintain consistency with the requirements for ibuprofen, mefenamic acid and naproxen. • The MEC recommended that the following warning statements from the SUSDP for oral ibuprofen and the ARGOM requirements for ibuprofen preparations for external use be included in the SUSDP warning statements for exempt ibuprofen and diclofenac as well as for S2 indomethacin preparations for external use: ! “Do not use [this product / name of product] if you are allergic to ibuprofen, aspirin or other anti-inflammatory medicines.” ! “Unless a doctor has told you to, do not use [this product / name of product] if you have asthma.”

This recommendation was made on the basis that the exempt preparations of ibuprofen and diclofenac for external use as well as the S2 indomethacin preparations for external use did not have any SUSDP labelling requirements.

• The MEC recommended that WS 101 and 104 in Appendix F, Part 1 should apply to OTC products containing ketoprofen and flurbiprofen to maintain uniformity with all NSAIDs and on the basis that the following NSAIDs which are included in S2 or S3 for specific situations are not listed in Appendix F, Part 3: ketoprofen, flurbiprofen, benzydamine, indomethacin and phenazone. However, the MEC was of the view that WS were not necessary for benzydamine or phenazone as their pharmacological properties are not consistent with those of other NSAIDs. • Overall, the MEC agreed that most of the above recommendations be brought to the attention of the NDPSC. The MEC also advised that the other recommendations including the warning against use in patients with impaired kidney function or heart failure and the inclusion of new mandatory label requirements for non-prescription ketoprofen, flurbiprofen and topical preparations of diclofenac, ibuprofen and indomethacin should be addressed in the Required Advisory Statements for Medicine Labels (RASML) after 1 July 2005. The Committee supported in-principle the recommendations from the MEC relating to the warning statements for non-prescription NSAIDs. However, the Committee was informed of Industry’s concerns regarding repeated changes to non-prescription NSAIDs label advisory statements. The Committee agreed to take the approach of referring back to the MEC all the labelling amendments recommended for non-prescription NSAIDs considered at the August and December 2004 MEC meetings for inclusion in the RASML first prior to adoption into the SUSDP, if required. This approach should facilitate the implementation of all label changes as one package as opposed to the implementation of several sets of amendments with varying dates of effect. Furthermore, the Committee agreed that this approach would put into effect revised arrangements for medicine

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labelling in which the OTC Section has the overall responsibility of maintaining and implementing the RASML. In addition, it was agreed that should the resulting changes come into effect during the transition phase (ie. prior to 1 July 2006), these changes would be included in Appendix F to maintain consistency with the RASML.

Required Asthma Warning Statements

The Committee was advised that the OTC Medicines Section had requested advice from the jurisdictions on 3 December 2004 concerning XXXXXXXXX’ application to revise their labelling for XXXXXXXXX products. The sponsor had proposed to include the following warning statement on asthma on the labelling of exempt and scheduled XXXXXXXXX products: “Before use – seek medical advice if…you suffer asthma. Most asthmatics can take XXXXXXXXX, but if you are sensitive to ibuprofen, aspirin or other pain relievers do not take this product.” For comparison, the recommended SUSDP wording for exempt ibuprofen is “Unless a doctor has told you to, don’t use [this product / name of the product] if you have asthma.”

The Committee noted that the jurisdictional members concurred with the view of the OTC Medicine Section that the proposed statement should not be used on unscheduled ibuprofen products given that professional advice would not be available at the point of purchase for such products. Members therefore noted that the consequential wording approved by the OTC Medicine Section in relation to the asthma warning statement for exempt and scheduled XXXXXXXXX product labels was: “Before use – seek medical advice if…you suffer asthma.” For scheduled XXXXXXXXX products, the additional wording “Most asthmatics can take XXXXXXXXX, but if you are sensitive to ibuprofen, aspirin or other pain relievers do not take this product.” was included in a separate section under “Answers to frequently asked questions.”

Pre-meeting comments

The Committee noted that pre-meeting comments had been received from XXXXXXXXX, XXXXXXXXX and XXXXXXXXX in support of the proposal to remove the duplication of the warning against prolonged use for unscheduled ibuprofen and maintain consistency between the SUSDP entries for various analgesic ingredients. XXXXXXXXX also highlighted the issue in relation to the readability of products labels due to the number of WS required and was concerned with the supply of medicines where professional advice was not available at the point of sale.

Members noted that XXXXXXXXX was of the view that the warning statements required for unscheduled ibuprofen should be consistent with those required for similar unscheduled analgesic products such as aspirin and paracetamol. The sponsor also raised the issue of increased compliance cost and inconvenience to the industry from the numerous amendments made to the labelling requirements following the June 2003 initial decision to reschedule ibuprofen. On this basis, the sponsor duly requested that a 12- month transition period be provided should further changes be recommended to enable all

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affected sponsors to implement any change with minimal disruption to product supply and allow sufficient time for compliance.

The Committee also noted two other public submissions relating to ibuprofen:

• XXXXXXXXX requested that the NDPSC revisit the statement made by a Committee member at the June 2004 meeting “that increased uncontrolled exposure to NSAID is not safe, a point raised by many of the pharmacy submissions”. XXXXXXXXX claimed to have suffered a severe anaphylactic episode in September 2004 in which a Specialist Immunologist had identified XXXXXXXXX as a trigger. However, members noted that some points in the submission were unclear but agreed to refer the submission to the Australian Drug Reactions Unit (ADRU) for consideration. • XXXXXXXXX, a moderator of an online information/support website for abusers of codeine informed that the most abused OTC codeine preparation in Australia was XXXXXXXXX based on the 500+ addicts that had visited the website. In addition, addicts easily learnt how to separate codeine from ibuprofen, which was far too simple with XXXXXXXXX. For those that did not separate codeine, the addicts were taking large daily doses of ibuprofen and codeine (up to 100 tablets a day). XXXXXXXXX asked the Committee to comment on this issue and consider rescheduling XXXXXXXXX to Pharmacist-Only Medicine. [Sentence deleted] Members agreed that this may be a formulation issue for consideration at the June 2005 meeting and advice XXXXXXXXX accordingly. DECISION 2005/43 - 14

The Committee agreed to delete the warning statements on prolonged use specified under (b)(iv) in the existing S2 ibuprofen entry to remove the duplication and maintain consistency between the entries for scheduled and exempt ibuprofen, aspirin and paracetamol. The Committee noted that this amendment still retained the full intent of the label warnings for exempt ibuprofen in divided preparations given that the warning statement against prolonged use would be retained under (b)(v) of the ibuprofen entry in S2 and therefore was not expected to compromise public health and safety. Furthermore, State and Territory members also agreed on a transition period where it would allow the relevant exempt products to comply with both the old (as published in SUSDP 19 Amendment 1) and the amended label requirements (agreed at this meeting) specified in the S2 entry for ibuprofen before 1 September 2005, but that from this date the amended label requirements would become mandatory.

Schedule 2 – Amendment:

IBUPROFEN – amend entry to read:

IBUPROFEN in preparations for oral use when labelled with a recommended daily dose of 1200 mg or less of ibuprofen:

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(a) in liquid preparations when sold in the manufacturer’s original pack containing 4 grams or less of ibuprofen; or

(b) in divided preparations, each containing 200 mg or less of ibuprofen, in packs of 100 or less dosage units except when:

(i) as the only therapeutically active constituent other than an effervescent agent;

(ii) packed in blister or strip packaging or in a container with a child-resistant closure;

(iii) in a primary pack of 25 or less dosage units;

(iv) the primary pack is labelled with warning statements to the following effect:

Don’t use [this product / name of the product]: If you have a stomach ulcer In the last 3 months of pregnancy [This statement may be omitted in preparations used exclusively for the treatment of dysmenorrhoea] If you are allergic to ibuprofen or other anti- inflammatory medicines; and

Unless a doctor has told you to, don’t use [this product / name of the product]: For more than a few days at a time With other medicines containing ibuprofen or other anti-inflammatory medicines or other medicines that you are taking regularly If you have asthma In children 6 years of age or less If you are aged 65 years or over If you are pregnant [This statement may be omitted in preparations used exclusively for the treatment of dysmenorrhoea].

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14. PROPOSED CHANGES/ADDITIONS TO THE STANDARD FOR THE UNIFORM SCHEDULING OF DRUGS AND POISONS.

14.1 SUSDP, PART 4

14.1.1 OSELTAMIVIR

PURPOSE

The Committee considered an application to reschedule oseltamivir from Schedule 4 (S4) to S3 with inclusion in Appendix H of the SUSDP.

BACKGROUND

Oseltamivir is a pro-drug of the active metabolite oseltamivir carboxylate. The active metabolite selectively inhibits influenza virus neuraminidase enzymes which are essential for the replication of both influenza A and B viruses. Oseltamivir is not a substrate for or inhibitor of the cytochrome P450 isoforms.

The November 2000 NDPSC meeting agreed to include oseltamivir in S4 of the SUSDP following the June 2000 ADEC meeting’s recommendation to approve an application by XXXXXXXXX to register XXXXXXXXX capsules, containing 75 mg of oseltamivir phosphate, for the treatment of infections due to Influenza A and B viruses in adults and children aged twelve years and older. XXXXXXXXX was then launched in Australia as an S4 medicine in January 2001. A later application by the sponsor to extend the indications of XXXXXXXXX to include the prophylaxis of influenza in adults and adolescents aged 13 years and older was recommended for approval by the ADEC at the April 2002 ADEC meeting.

The October 2004 NDPSC meeting considered an application to reschedule oseltamivir from S4 to S3 for the treatment and prevention of infections due to influenza A and B viruses in adults and adolescents 13 years of age and over, with inclusion in Appendix H. The NDPSC at the time considered the available data inadequate in providing a reassurance that widening the availability of oseltamivir for the treatment of influenza to S3 would not facilitate the spread of resistance to neuraminidase inhibitor (NI) class of drugs. In addition, the NDPSC considered that an optimised point-of-care test should be incorporated into the S3 treatment algorithm for XXXXXXXXX. Furthermore, members considered it important to the Committee’s consideration if advice was received from authorities that deal with communicable diseases to gain an understanding of the implications an S3 availability of oseltamivir for the treatment of influenza would have on the national strategies for managing influenza epidemics or pandemics. Therefore, the NDPSC agreed to defer making a decision to the February 2005 meeting to allow input by XXXXXXXXX.

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DISCUSSION

The Committee noted the comments received from NIPAC which focused on two critical issues concerning resistance and depletion of stocks during an epidemic or pandemic and the paucity of data on these two issues. NIPAC highlighted the following:

• Increased resistance to oseltamivir from wider usage a significant concern. The process of resistance development in neuraminidase inhibitors from the only data available indicates that mechanism of resistance also destroys the ability to replicate effectively and hence reduces transmissibility and likelihood of further generation of resistance. It was put forward that the development of resistance that did not also cause reduction of replication would be unlikely and requires a major genetic change. Some of the NIPAC members felt that the data was insufficient to justify a definitive statement on this and that further reassurance was required through further research. In addition, although the resistant strains to date have not caused clinically significant illnesses there was no data available on, for example, the highly pathogenic avian influenza H5N1 subtype. • The management of influenza during a pandemic is also a critical issue. The availability of oseltamivir as an S3 or S4 medication would impact on supplies available during a pandemic. It would be possible that, as an S3 medication, overall supplies of oseltamivir in Australia would increase, however the ability to augment the stockpile may be reduced because of depletion of supplies through increased OTC sales in the event of a pandemic threat. Furthermore, an S3 schedule would also remove the possibility of using a potential strategy of working with general practitioners to ensure all available oseltamivir would be used to the greatest benefit. A detailed examination to predict how affected and non-affected people would behave during a pandemic and what this would mean in terms of usage especially in the S3 environment may assist in resolving this issue. • Other issues raised by NIPAC include: − An S3 status would most likely permit more timely initiation of therapy but could impact on the responsibilities and role of pharmacists.

− There might be a greater likelihood of inappropriate treatment through patients taking unnecessary medication.

− There might be less morbidity. However, claims of fewer deaths and lower rates of hospitalisation were not well-supported.

− There was inconclusive data on viral shedding and the consequences of the proposed use of oseltamivir for prophylaxis by the sponsor were unclear.

− The UK experience was not a suitable example as oseltamivir use occurred under quite strict guidelines and NIPAC was not aware of any country where oseltamivir is available without prescription.

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• The Neuraminidase Inhibitor Susceptibility Network (NISN) is currently working with the WHO Collaborating Centre on Influenza in Japan to assess the likelihood of community transmission of resistant strains. These NISN trials are expected to be completed by middle of this year. Due to the seriousness with which NIPAC viewed this matter, it was requested that further consideration of the rescheduling of oseltamivir should be delayed until the NISN trials are completed in order for NIPAC to make a final recommendation with the additional information. A member advised there is a potential for substantial use of oseltamivir in non-influenza infected subjects based on clinical or self-diagnosis. It was stated that in clinical trials submitted to support registration of the neuraminidase inhibitor drugs, about two-thirds of subjects with clinically diagnosed influenza enrolled in at a time of epidemic had laboratory confirmed influenza virus infection. Members noted that there were no registered rapid diagnostic tests for influenza diagnosis at the time.

Members noted the post-meeting comment received from the sponsor, addressing the following matters raised at the October 2004 NDPSC meeting:

• Both the evaluator for the application and the NDPSC had considered that point-of- care tests should be incorporated into the S3 treatment algorithm for XXXXXXXXX. However, the sponsor was of the view that this is inappropriate and unnecessary for the rescheduling of XXXXXXXXX due to the limitations of current tests. The sponsor cited numerous references indicating the limitations of such testing and also reasoned that it would be an anomalous requirement for a pharmacist to carry out such testing prior to providing XXXXXXXXX when this is not a requirement for the medical profession. By placing an additional burden on pharmacies that is not placed on the medical profession would delay access to XXXXXXXXX. • The NDPSC had noted the advice from the Expert Advisory Group on Antimicrobial Resistance (EAGAR) supporting the evaluator’s recommendation that oseltamivir remain in S4. However, the sponsor commented that the terms of reference for the EAGAR is to provide strategic, independent, expert advice on antibiotic resistance. The sponsor reiterated that in adolescents and adults with confirmed influenza illness, appropriate treatment with XXXXXXXXX significantly reduces antibiotic use, evident from the pivotal trial conducted during the development of XXXXXXXXX and in a prospective analysis of 10 placebo-controlled, double blind trials of XXXXXXXXX treatment. • In relation to S3 supply and pandemic preparedness, the sponsor contended that S3 supply of XXXXXXXXX would compliment the Pandemic Plan. The sponsor quoted the following comment from a workshop summary report by the Institute of Medicine of the National Academies, Board of Global Health with respect to the threat of pandemic influenza: “Only two manufacturers produce these [neuraminidase inhibitor] compounds, and their existing surge capacity is unlikely to meet pandemic demand. One means to increase the availability of neuraminidase inhibitors is…to make greater

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use of the product in treating and preventing influenza in interpandemic seasons, with the expectation that capacity for its production will rise with demand” (Knobler et al, The National Academic Press 2004)

The quote suggested that making greater use of these medicines during interpandemic seasons, as the sponsor suggested would happen if XXXXXXXXX becomes S3, would likely increase the capacity for production as demand will increase.

However, a member highlighted that the workshop summary report included comments on the inappropriate use and resistance to neuraminidase inhibitors. The member indicated that participants in the workshop were alerted to the danger posed by the inappropriate use of antiviral medications during a pandemic which apparently occurred during the recent Asian H5N1 epidemic. The report stated that patients who took medicines like oseltamivir for only two or three days instead of the recommended five days continued to shed virus that is potentially resistant to oseltamivir although they gained significant relief from flu symptoms. Moreover, the report referred to an article (Kiso et al, Lancet 2004) which documented higher than previously observed frequency of antiviral resistance in infants and young children treated with oseltamivir in Japan. Members noted that on these grounds, there was a compelling need to obtain further information about the incidence and mechanisms of resistance to the neuraminidase inhibitors.

Members noted that XXXXXXXXX supported the sponsor’s application and that it had agreed to work with the sponsor to develop educational materials for pharmacists to ensure that the professional advice and support provided to Australian consumers would be of the highest standard.

The Committee noted that the sponsor had applied for an Appendix H listing. However, members agreed that the rescheduling application should first be resolved before considering the Appendix H application.

OUTCOME

The Committee considered that further data and information were required on the use of oseltamivir in relation to the consequences of prophylactic use, the potential to develop resistance through broader public availability as an S3 medication and the influence of the scheduling status during a pandemic. The Committee therefore agreed to defer further consideration of the rescheduling of oseltamivir until the NISN trials were completed. This approach would allow NIPAC to consider further scientific data in order to make a final recommendation to the NDPSC on this matter.

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14.1.2 DIPHENHYDRAMINE

PURPOSE

The Committee considered a proposal to amend the Schedule 2 (S2) entry for diphenhydramine.

BACKGROUND

The October 2002 meeting of the Trans-Tasman Harmonisation Working Party (TTHWP) recommended that New Zealand harmonise with Australia the scheduling of antihistamine preparations combined with other active ingredients including codeine, paracetamol and pseudoephedrine using the following broad principles (TTHWP Decision 8/8): (i) antihistamines and preparations with a significant potential for abuse be included in S4/Part 1; (ii) single-active preparations of sedating antihistamines be included in S3/Part II; and (iii) single-active preparations of non-sedating antihistamines and specified combination preparations of antihistamines be included in S2/Part III.

The October 2003 NDPSC meeting agreed to foreshadow consequential amendments to the SUSDP to align scheduling with the registration status of existing products while maintaining consistency with the recommendations of TTHWP Decision 8/8.

The February 2004 NDPSC meeting accordingly amended the SUSDP S2 entries as foreshadowed for sedating antihistamines such that the S2 entry for diphenhydramine and other oral sedating antihistamines (brompheniramine, chlorpheniramine, dexchlorpheniramine, diphenylpyraline, doxylamine, pheniramine, promethazine, thenyldiamine, trimeprazine and triprolidine) were amended to address the concerns about the sedating effects of the antihistamines. Consequently, preparations for the treatment of symptoms of coughs, colds or influenza when combined with a sedating antihistamine were classified as S2 with at least one of the other therapeutically active substances is a sympathomimetic decongestant or when in a day-night pack with the dose containing the sedating antihistamine is labelled for bed-time dose. This amendment was given effect from 1 September 2004.

DISCUSSION

The Committee noted the following concerns highlighted by XXXXXXXXX regarding some inadvertent impacts of the scheduling changes to the diphenhydramine entry:

• Prior to the amendment of the S2 entry for diphenhydramine, there were already a number of S2 oral preparations in the Australian market containing diphenhydramine in combination with other active substances indicated for the treatment of symptoms of coughs, colds or influenza. This was supported by the fact that “diphenhydramine are frequently employed as cough suppressants in compound preparations” (Martindale – The Complete Drug Reference – Monographs, Cough Suppressants Expectorants Mucolytics and Nasal Decongestants).

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• Following the amendment to the diphenhydramine S2 entry, some diphenhydramine oral preparations were up-scheduled from S2 to S3. Consequently, oral preparations for the treatment of symptoms of coughs, colds or influenza that contain diphenhydramine, when in combination with at least one therapeutically active substance that is not a sympathomimetic decongestant, are now S3. Two products of the sponsor had been affected by the amendment: (i) XXXXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX (XXXXXXXXX) Active ingredients: diphenhydramine hydrochloride, ammonium chloride and sodium citrate. (ii) XXXXXXXXX XXXXXXXXX XXXXXXXXX XXXXXXXXX (XXXXXXXXX) Active ingredients: diphenhydramine hydrochloride and dextromethorphan hydrochloride. • The sponsor proposed an amendment to the wording for the diphenhydramine S2 entry to allow products for the treatment of symptoms of coughs, colds or influenza that do not contain a sympathomimetic decongestant (such as an antitussive or an expectorant) as at least one of the therapeutically active substances when in combination with diphenhydramine to remain in S2 whilst retaining hypnotic preparations in S3. The Committee also noted the following concerns from XXXXXXXXX as stated in their pre-meeting comments:

• In view of the TTHWP objectives, XXXXXXXXX could not comprehend the need for the inclusion of a sympathomimetic decongestant in every sedating antihistamine combination product that is indicated for daytime use for the treatment of coughs, colds and influenza given that the Record of Reasons of the February 2004 NDPSC meeting stated that “the restrictions requiring the sedating antihistamine to be combined with another therapeutically active substance should minimise the risk of abuse” and that “because of different interpretations of the S2 entry relating to combination products for treating the symptoms of coughs, cold and influenza, combination products containing sedating antihistamines had been on the market as S2 products for some time in Australia and New Zealand without any evidence of abuse”. • As it appeared from the Records of Reasons that the NDPSC did not consider abuse to be an issue per se, XXXXXXXXX considered that the scheduling amendments did not meet the criteria put forward by the NDPSC in that they do not allow for: (i) S2 oral sedating antihistamine combinations that do not include a sympathomimetic decongestant, ie: S2 antitussive (including codeine/antihistamine combinations) and S2 expectorant/antihistamine combinations

(i) Night time products that are not part of day-night packs

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(ii) Removal of the specificity from existing sedating antihistamine entries in the SUSDP to allow the inclusion of wider range of substances in combination antihistamine preparations.

The Committee also noted the late pre-meeting submission from XXXXXXXXX concerning their product XXXXXXXXX containing promethazine and pholcodine. The sponsor reiterated that the statement from the Record of Reasons of the February 2004 NDPSC meeting “the Committee were not aware of specific abuse problems with promethazine” was confirmed by the lack of reports of abuse after performing a Medline literature search. The sponsor was also of the view that by allowing products that contain pseudoephedrine in combination with sedating antihistamines to be S2 were contrary to industry trends by effectively promoting the proliferation of products containing pseudoephedrine which the pharmaceutical industries and law enforcement agencies have been campaigning against. In addition, the sponsor contended that this decision might encourage pharmaceutical companies to register combination pseudoephedrine formulations as S2 medicines.

In light of the recent comments from stakeholders, the Chair highlighted that the Committee had gazetted the foreshadowed decision on sedating antihistamines which provided stakeholders with ample opportunity to provide public comment.

Members were also advised that the NZ Medicines Classification Committee (MCC) would be considering the final review of antihistamines at its May 2005 meeting. It was noted that the November 2004 MCC meeting had agreed to accept the broad principals of the NDPSC with regard to the classification of sedating antihistamines except when applied to the following types of products which would move to restricted medicine in NZ:

• Travel sickness products containing cyclizine in travel packs that were not exempt from scheduling in NZ while some other antihistamine travel sickness products in travel packs were exempt. • Night-time only capsules containing paracetamol and diphenhydramine. • Paediatric liquid preparations containing paracetamol and doxylamine. • Tablets containing paracetamol, codeine and doxylamine. The MCC was of the view that the NDPSC had appeared not to have taken the above products into account in their consideration. The MCC had therefore agreed that comments from XXXXXXXXX, XXXXXXXXX and the relevant sponsors of the above products should be sought on the proposed reclassification. The MCC had also decided to delay implementation of the changes in the gazette until a further round of consultation had been undertaken based on the proposed schedule wording for each individual antihistamine.

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In light of the forthcoming final review of antihistamines by the MCC in May and in anticipation of achieving Trans-Tasman Harmonisation, members agreed that the minutes of the May 2005 MCC meeting be requested in time for the June 2005 NDPSC meeting for the Committee’s consideration of any outcomes from the MCC meeting regarding the scheduling of oral sedating antihistamines.

OUTCOME

The Committee agreed to foreshadow the consideration of the scheduling of oral sedating antihistamines relating to any outcomes on this issue from the April 2005 MCC meeting in anticipation of achieving Trans-Tasman Harmonisation.

14.1.3 DICLOFENAC

PURPOSE

The Committee considered an application to reschedule diclofenac in divided preparations for oral use containing 12.5 mg or less per dosage unit in a pack containing 30 or less dosage units from Schedule 3 (S3) to S2.

BACKGROUND

Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) that exhibits pronounced anti-inflammatory, analgesic and anti-pyretic properties by inhibiting prostaglandin synthesis through inhibition of cyclo-oxygenase-1 (COX-1) and COX-2. In 1986 a formulation containing immediate release diclofenac potassium 25 mg and 50 mg tablets was launched as XXXXXXXXX and XXXXXXXXX designed for short-term treatment of acute painful and inflammatory conditions. XXXXXXXXX products are available in over 80 countries including Australia, New Zealand, the European Union and USA. The fast acting diclofenac potassium formulation is generally intended for acute pain relief and/or short-term (up to one week treatment) while diclofenac sodium is claimed to be more appropriate for chronic pain states including rheumatoid arthritis and osteoarthritis.

Diclofenac was included in S4 in March 1981. The NDPSC then agreed to reschedule diclofenac 25 mg or less in packs of 30 or less for oral use to S3 in August 1999 as recommended by the TTHWP and listed it in Appendix H of the SUSDP in August 2001.

The June 2004 NDSPC meeting considered an application by XXXXXXXXX to reschedule diclofenac from S3 to S2 in divided preparations for oral use containing 12.5 mg or less per dosage unit in packs of 30 or less. The NDPSC noted that the sponsor had also lodged a parallel application to register XXXXXXXXX (diclofenac potassium 12.5 mg) tablets in packs of 10 and 20 tablets with the OTC Medicines Section with the following indications: temporary relief of headache, dental pain, period pain, rheumatic and muscular pain, back ache; temporary relief of symptoms of cold and flu including aches and pains, sore throat pain; and reduction of fever. The dosage recommendation was an initial dose of two x 12.5 mg tablets and continued with one or two tablets every

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four to six hours if needed with a maximum dose of six tablets in a 24-hour period. However, the NDPSC did not agree with the proposal as members were not convinced that rescheduling diclofenac 12.5 mg to S2 was appropriate at the time in the absence of an evaluation for OTC registration and in the absence of local post-marketing experience with the 12.5 mg oral dose formulation in Australia to establish the safety, efficacy and use pattern for the indications sought for the product.

Subsequently, the sponsor provided additional materials for consideration at the October 2004 meeting in response to the outcome of the June 2004 meeting for diclofenac 12.5 mg. However, as the submission was received after the publication of the pre-October 2004 meeting gazette notice, the October 2004 NDPSC meeting could not consider the submission without appropriate public consultation. Furthermore, the NDPSC was informed that the MEC Secretariat had requested additional data from the sponsor to allow finalisation of the evaluation report for the registration of diclofenac 12.5 mg.

The October 2004 NDPSC meeting also reviewed the current assessment process for the rescheduling of medicines where product formulations had not been previously marketed in Australia. Members agreed that the NDPSC should continue to reserve the right to request additional data in order to make appropriate scheduling decision, or await receipt of a detailed registration evaluation report of a product undergoing parallel assessment through the registration and scheduling processes.

DISCUSSION

Safety and efficacy

The Committee was advised that the evaluation report for OTC registration of diclofenac 12.5 mg was not yet available for consideration at this meeting. Consequently, some members restated the concern that in order to determine the overall assessment of its safety profile, it was important to establish the efficacy of diclofenac 12.5 mg in treating all pain states covered in the proposed indications. Members noted that the proposed indications for diclofenac 12.5 mg differed to some extent from the indications already approved by the TGA for diclofenac 25 mg which included the following: short-term treatment (up to one week) for the relief of acute pain states in which there is an inflammatory component; treatment of acute migraine attacks (with or without aura); and symptomatic treatment of dysmenorrhoea. Members remained concerned that the absence of an Australian experience with diclofenac 12.5 mg as an S2 medicine could potentially lead to inappropriate use of the product as without consumer familiarity with the product, the overall OTC availability of diclofenac in more than one dosage strength for similar indications could confuse consumers particularly given that pharmacists may not have the opportunity to provide counselling to those who would self-select the S2 diclofenac 12.5 mg.

The Committee considered the sponsor’s response to the above concerns as detailed in their submission to the October 2004 NDPSC meeting. The sponsor had raised the following points:

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• The NDPSC evaluates proposals for reclassification of therapeutic substances predominantly on the basis of available post-marketing experience (both locally and overseas) with the substance, not specific formulations of that substance. • A decision to reschedule diclofenac 12.5 mg to S2 does not guarantee a right to market. In addition, the MEC would not recommend marketing approval if the data submitted did not support the requested dosage and indications. • Diclofenac has been available as an S4 medicine in Australia for more than 23 years. The availability of diclofenac 25 mg as an S3 medicine in Australia since March 2000 clearly demonstrated that the local OTC experience with this dose form. In addition, international safety reports for diclofenac from the most recent clinical studies in almost 5000 patients, post-marketing surveillance studies of more than 100000 subjects and spontaneous adverse reaction reports from a usage base of more than one billion subject, provided overwhelming evidence in support of the safety profile of diclofenac. Moreover, at the time of the original rescheduling submission, diclofenac 12.5 mg was already marketed in nine European countries, thereby providing substantial evidence of safety from overseas post-marketing surveillance. • Data provided with the original submission demonstrated that diclofenac 12.5 mg was equivalent in both efficacy and safety to ibuprofen 200 mg. • The available information should provide a reasonable basis for rescheduling all existing S3 presentations (ie. oral diclofenac 25 mg and lower strengths) to S2 regardless of formulations or evaluation status. The Committee recalled that the efficacy data provided with the original rescheduling submission were in the form of reviews and not individual studies. Members noted from the reviews that the efficacy data were based on a series of placebo controlled blinded comparison studies as well as comparison studies with ibuprofen and paracetamol. The low dose clinical trials reviewed were conducted in almost 3000 subjects who were treated for dental pain, benign febrile sore throat, headache, period pain, symptoms of cold and flu/fever and rheumatic and muscular pain/backache. The reviews suggested that these studies showed that overall diclofenac 12.5 mg was equally as effective as ibuprofen 200 mg and paracetamol 500 mg when compared with daily doses of diclofenac 75 mg (6 x 12.5 mg tablets), ibuprofen 1200 mg (6 x 200 mg) and paracetamol 3000 mg (6 x 500 mg).

Members noted the pre-meeting comments received from XXXXXXXXX, XXXXXXXXX, XXXXXXXXX and XXXXXXXXX. All respondents with the exception of XXXXXXXXX opposed the proposal to reschedule diclofenac 12.5 mg from S3 to S2 due to the following reasons:

• Recent developments suggested increased cardiovascular risks from NSAIDs, particularly when used for long periods. In particular, the FDA had issued a statement in December 2004 that preliminary results from a long-term clinical trial (up to three years) suggesting that long term use of the NSAID naproxen may be associated with increased cardiovascular risk compared to placebo.

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Members noted that while the results of these studies were preliminary and in conflict with other study data on NSAIDs and cyclooxygenase-2 (COX-2) inhibitors, the FDA had advised that, as an interim measure pending further review of data, consumers were to be advised that all OTC pain medications including NSAIDs should be used in strict accordance with the label directions and if use of an OTC NSAID was needed for longer than ten days then a physician should be consulted.

The Committee noted that the recommended duration of treatment proposed for diclofenac 12.5 mg was not to exceed five days for pain relief and three days for treatment of fever, and that the dosage was not to exceed six tablets per day.

• The guidelines for best practice in NSAID recommendation included the use of paracetamol first-line for mild to moderate pain and OTC NSAIDs primarily for acute symptom relief and not chronic therapy. Should diclofenac tablets be made S2 there would be conflicting messages from professional practice and the regulator and marketing messages to consumers. Members noted that diclofenac 12.5 mg was proposed for acute pain relief with treatment duration not exceeding five days and the indications were those already approved for unscheduled or S2 presentations of other analgesics. In addition, the sponsor highlighted to the Committee that there were already NSAID products comparable to diclofenac 12.5 mg which were available as unscheduled or S2 medicines including ibuprofen, naproxen and mefenamic acid.

• In the context of the Australian market place, the potential difference in the availability of diclofenac 25 mg (S3) and diclofenac 12.5 mg (S2) could potentially lead to confusion by consumers given that the diclofenac 12.5 mg bought without pharmacist intervention could only be used for headaches and fevers whereas the diclofenac 25 mg tablets bought from the pharmacist could be used to treat painful conditions but not headaches. Members, however, acknowledged the sponsor’s point that the following substances were available as unscheduled or S2 medicines in different strengths: (i) aspirin in strengths ranging from 250 to 650 mg either as a single active ingredient or in combination with chlorpheniramine, codeine and phenylephrine; (ii) ibuprofen as a single active ingredient or with codeine or pseudoephedrine; and (iii) paracetamol in strengths ranging from 325 to 665 mg with or without various combinations of codeine, pseudoephedrine, dextromethorphan and chlorpheniramine. The sponsor justified that although these products have overlapping indications and dosages, these did not appear to have led to general misuse, confusion or adverse outcomes related to consumers self-diagnosing everyday maladies and self-selecting treatments from among these products. Therefore, the sponsor contended that it would be similarly unlikely that confusion would arise with two OTC strengths of diclofenac.

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Trans-Tasman Harmonisation

The Committee noted the November 2002 NZ MCC meeting agreed to classify diclofenac 12.5 mg tablets or capsules to Pharmacy-Only medicine. Members noted the following points were taken into account in the deliberations of the MCC:

• Data provided to the MCC included a comparison of diclofenac with naproxen on the grounds that since naproxen was safe for pharmacy-only sale then diclofenac would similarly be safe for sale at that level. • No comparative studies with ibuprofen were provided by the sponsor which the MCC considered to be a more appropriate benchmark. However, other data reviewed at the meeting indicated that the daily dose of diclofenac 12.5 mg was comparable in safety as the daily dose of 1200 mg of ibuprofen. • The incidence rate of hepatic damage which appeared to be marginally higher than ibuprofen had been difficult to assess as the MCC had not been given access to the papers which referred to hepatic damage. • However, the MCC agreed that the potential for misuse with diclofenac 12.5 mg was low and there was a need for consistency given that naproxen 250 mg tablets were already available as pharmacy-only medicine and that there were no limits to the amount of aspirin in available formulations despite its side effects. It was agreed therefore that diclofenac 12.5 mg tablets should similarly be made available as pharmacy-only medicines when sold in packs of not more than 20 tablets. In relation to the issue on hepatic damage raised by the NZ MCC, the Committee noted that the sponsor’s original submission to the NDPSC included a three-month hepatic safety trial undertaken in patients receiving (i) diclofenac 37.5 mg and 75 mg per day or low dose ibuprofen 1200 mg per day for mild to moderate osteoarthritis or (ii) high dose diclofenac potassium 150 mg per day or diclofenac sodium 300 mg per day for moderate to severe osteoarthritis. The study demonstrated that there were no liver transaminases elevations at day 10 visits (range 7-13 days). During the three-month study period, there was only one marked (suspected hepatitis A) and five meaningful transaminase increases each in the 37.5 mg group and 75 mg group and one meaningful increase (suspected blood sample haemolysis) in the ibuprofen group. It was noted that none of the transaminase increases were accompanied by symptoms and that all cases reverted to normal levels after cessation of intake. It was also noted that there was no evidence from safety monitoring in the clinical trial dataset that low-dose diclofenac caused any clinically relevant adverse events in the urogenital or renal systems.

As the Committee was aware of the need to give due consideration to public health and safety issues under the harmonisation principles, members noted the following safety information based on the assessment by the NDPSC evaluator of data made available to the Committee:

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• Post-marketing surveillance data showed that diclofenac 12.5 mg was launched in nine countries (Switzerland, Norway, Hungary, Netherlands, Poland, Russia, Israel, Germany and Vietnam). It was estimated that around 5.8 million patients had received diclofenac potassium 12.5 mg tablets between September 2000 and June 2004 and that during this time, nine spontaneous adverse event reports were associated with the product; line listings revealed that these were mostly consumer reports and only one of these was a serious listed report of a patient on polypharmacy (XXXXXXXXX [diclofenac 12.5 mg] for back pain, XXXXXXXXX for back pain and XXXXXXXXX for a urinary tract infection) who developed a bullous rash on the feet after three days. The remaining eight reports were non-serious and included individual reports of mucosal oedema, eyelid oedema, peripheral oedema, muscle contractions, menorrhagia, delay in menses, pruritus and “suffocation feeling”. • The evaluator noted that an ADRAC listing was provided on adverse events associated with diclofenac 25 mg and 50 mg preparations. However, corresponding information was not made available on denominator of numbers, total daily dose or duration of exposure and the individual adverse events included showed no particular pattern. There were more than 10 cases each of adverse events such as diarrhoea, anorexia, renal impairment, pruritus, rash, haematemesis, melaena, anaemia, abdominal pain, duodenal ulcer, dyspepsia, flatulence, gastric ulcer, glossitis, mouth ulceration, nausea and vomiting. There were other isolated adverse events but with no particular pattern. • Large but uncontrolled post-marketing treatment studies with diclofenac 75 mg to 200 mg per day for up to two weeks (115000 subjects) in general practice revealed that the estimated overall incidence of adverse events was less than 20% and the vast majority of these were not serious. The overall estimated gastrointestinal complication was around 2.2 per 10000 patients although these studies had no comparator groups. • A published review of 162 open studies (Catalano, Am J Med 1986) suggested a low gastrointestinal (GI) incidence rate of 7.6% reported with prescribed diclofenac sodium in the studies conducted from 1972 to 1982 in 85361 patients and that the proportion of people having serious GI adverse events was 1.17 per 10000 patients. • Based on the overall data provided, the safety profile of diclofenac could be reasonably extrapolated to support the safety of the low-dose regimen proposed for non-prescription use of up to 75 mg per day. Members also noted that XXXXXXXXX supported the proposal to reschedule diclofenac 12.5 mg on the grounds of Trans-Tasman harmonisation.

Appendix F, Part 3 warning statements for diclofenac

Members acknowledged that the June 2004 NDPSC meeting noted that there was no entry in Appendix F, Part 3 of the SUSDP for diclofenac and that the sponsor did not propose any warning statement for the proposed S2 product. However, the sponsor had assured in their October 2004 submission that S2 presentations of diclofenac would carry

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similar mandated warnings as other S2 or unscheduled NSAIDs. To this end, the Committee agreed to include appropriate warning statements for diclofenac in Appendix F, Part 3.

DECISION 2005/43 - 15

The Committee agreed to include in Schedule 2 of the SUSDP diclofenac in preparations containing 12.5 mg or less per dose in packs containing not more than 20 tablets or capsules. The Committee was convinced that the available data including results of clinical trials and post-marketing safety data supported an acceptable safety profile of diclofenac 12.5 mg at a daily dose of up to 75 mg consistent with S2 medicines. Members also agreed that this decision would harmonise the scheduling of diclofenac 12.5 mg with NZ. The Committee also agreed to include appropriate warning statements for diclofenac in Appendix F, Part 3 of the SUSDP.

Schedule 2 - New entry

DICLOFENAC in divided preparations for oral use containing 12.5 mg or less of diclofenac per dosage unit in a pack containing 20 or less dosage units and labelled with a recommended daily dose of 75 mg or less of diclofenac.

Schedule 3 – Amendment

DICLOFENAC in divided preparations for oral use containing 25 mg or less of diclofenac per dosage unit in a pack containing 30 or less dosage units except when included in Schedule 2.

Schedule 4 – Amendment

DICLOFENAC except:

(a) when included in Schedule 2 or 3; or

(b) in preparations for dermal use.

Appendix F, Part 3 – New entry

Poison Warning Statements

Diclofenac……………………………………101,104.

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14.2 SUSDP, PART 5

14.2.1 APPENDIX H

14.2.1.1 ORLISTAT

PURPOSE

The Committee considered a submission to include orlistat in Appendix H of the SUSDP.

BACKGROUND

Orlistat is a potent, specific and reversible long-acting inhibitor of gastrointestinal lipases which are required for the systemic absorption of dietary triglycerides. It is used in conjunction with dietary modification in the management of obesity.

Orlistat was first included in Schedule 4 (S4) of the SUSDP in November 1999 following a recommendation by the trans-Tasman Harmonisation Working Party (TTHWP). The December 1999 ADEC meeting had recommended the registration of XXXXXXXXX containing 120 mg of orlistat per capsule for the treatment of obese patients with a body mass index (BMI) ≥ 30 and overweight patients with a BMI ≥ 27 in the presence of other risk factors, in conjunction with a mildly hypocaloric diet. Since May 2000 XXXXXXXXX has been marketed in Australia by XXXXXXXXX.

Submissions to reschedule orlistat for the treatment of obesity from S4 to S3 were considered at both the June 2002 and February 2003 NDPSC meetings. The February 2003 submission also sought to have orlistat included in Appendix H. On both these occasions the NDPSC decided that the information submitted by the sponsor did not provide adequate evidence to address the Committee’s concerns in relation to its safety profile; the necessity for medical assessment to determine a patient’s suitability for treatment with orlistat; and the view that therapeutic intervention should not be the first- line treatment for obesity.

The October 2003 NDPSC meeting considered a third new submission to reschedule orlistat for the treatment of obesity from S4 to S3 without inclusion in Appendix H. The NDPSC agreed to reschedule orlistat from S4 to S3 for the treatment of obesity on the basis that the sponsor had provided adequate evidence addressing the Committee’s previous concerns. In making this decision, the NDPSC also took into account that several weight management programs/protocols had been developed by the sponsor and the pharmacy profession which were designed to assist consumers in achieving safe and long term weight loss with orlistat therapy.

The February 2004 NDPSC meeting confirmed the initial decision but also agreed to recommend to the MEC that the advice on vitamin supplementation including the dosage regimen be given stronger emphasis in the Product Information (PI) and Consumer

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Medicine Information (CMI ) documents to reinforce the importance of the issue to consumers.

The June 2004 NDPSC meeting noted that the information package on XXXXXXXXX and patient support programs developed by the sponsor and pharmacy groups were appropriate to assist pharmacists in providing advice to consumers to enhance the safety and efficacy of orlistat for the management of weight loss and treatment of obesity. The NDPSC also agreed that the sponsor be requested to amend the PI and CMI to include a list of vitamin supplements available on the Australian market containing the appropriate levels of fat-soluble vitamins that could be taken as an appropriate supplement when undertaking orlistat therapy to prevent the potential development of vitamin deficiency. However, the sponsor was of the view that it would not be appropriate to include a list of vitamin supplements in the PI or CMI due to the constantly changing scenes of the Australian market place. Alternatively, the sponsor undertook that it would continue to provide recommendations for appropriate amounts of vitamins to be taken in conjunction with orlistat therapy in the PI to guide consumers in selecting vitamin products.

The October 2004 NDPSC meeting considered advice from the ADEC relating to a submission from XXXXXXXXX highlighting the issue that orlistat could increase the risk of age related macular degeneration (ARMD). However, the NDPSC agreed that no further action from the Committee was required at the time in relation to the issue of ARMD and orlistat, as members were sufficiently reassured that this matter would be appropriately dealt with at the product registration level.

DISCUSSION

The Committee noted the following points raised by the sponsor in support of their proposal to include orlistat in Appendix H:

• Consumers are widely exposed to the promotion of questionable product claims that are not subjected to regulatory scrutiny and therefore consumers should be informed through branded advertising that XXXXXXXXX is a high quality product with realistic claims based on clinical evidence as distinct from other unproven OTC weight loss treatment options currently available from the pharmacy. • XXXXXXXXX should be promoted to overweight consumers as it is both safe and effective. It is also the only OTC weight loss medication designed to be used in conjunction with diet and exercise that satisfies NHMRC’s criteria for a weight loss agent, ie. any drug used to treat obesity should satisfy five important criteria: (i) the drug should reduce weight and weight-dependent conditions; (ii) the drug should have no addictive properties; (iii) the desirable effects of the drug must outweigh the hazards of the drug; (iv) the drug must be able to be used long term; and (v) the drug’s mechanism of action should be known.

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The sponsor contended that currently, advertised OTC weight loss agents do not meet some or all of the above criteria.

• Branded advertising would provide consumers with specific information about XXXXXXXXX to help them decide to see their pharmacist on whether XXXXXXXXX would be suitable for them and that the consumer must be counselled by a pharmacist if requested by brand name. Moreover, pharmacist intervention could potentially result in a referral to a GP if underlying obesity related disorders are suspected. The sponsor assured that all XXXXXXXXX advertisements would include words to the effect of: “Your pharmacist’s advice is required”. • The target audience for the branded advertising campaign would focus on individuals with high BMI who had made several attempts at losing weight but without success. Diet and exercise would be emphasised as the primary effective strategy for successful long term weight loss with XXXXXXXXX as an adjunct. • By facilitating a better informed community, branded advertising of XXXXXXXXX would be a necessary progression to promote its appropriate use without the danger of promoting unproven OTC treatments and thus, would increase weight loss outcomes that would translate into public health benefits. The Committee recalled the following concerns raised at the June 2002 meeting when the NDPSC considered the sponsor’s proposal to reschedule orlistat to S3 and include orlistat in Appendix H:

(i) that advertising may induce individuals with eating problems associated with anorexia and bulimia to use orlistat inappropriately; and

(ii) that advertising could create an unrealistic consumer expectation of the product and drive consumer demand. Members noted that the sponsor had responded to these concerns with the following justification in their submission:

! Use by inappropriate patient group (wrong BMI): Branded advertising would minimise inaccurate self diagnosis by targeting the consumer group for whom XXXXXXXXX was appropriate as they would be advised to ask their pharmacist if XXXXXXXXX was suitable for their condition. Overweight and obesity would be visually determined in the first instance followed by a simple BMI check. Branded advertising would also depict realistic representations of the people who might benefit from taking XXXXXXXXX. ! Misuse by anorexics and bulimics: Those with anorexia nervosa typically restrict food intake by fasting. As XXXXXXXXX would only inhibit fat absorption in the presence of dietary fat, there could be no pharmacological action in the fasting individual and therefore its use in this condition would be futile. On the other hand, bulimics would be deterred from XXXXXXXXX use since orlistat inhibits only 30% of ingested fat when compared to laxatives and vomiting which would result in the total content of the meal being eliminated, including essential nutrients and vitamins. The high cost of

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XXXXXXXXX relative to laxatives would also deter bulimics from purchasing the drug. ! Use with inappropriate diet: By providing consumers with the information to combine XXXXXXXXX with an appropriate diet in order to avoid gastrointestinal (GI) side effects that would be likely to occur following a high fat meal, consumers would understand the importance of reducing dietary fat intake. In addition, the knowledge of such GI side effects would discourage patients from using XXXXXXXXX to compensate for a high fat binge and reinforce behavioural modifications such as healthy eating habits that would be required for successful long term weight loss. Members noted the pre-meeting comments received from the following respondents in support of the proposal to include orlistat in Appendix H:

• XXXXXXXXX supported the inclusion of orlistat in Appendix H as it was of the opinion that by the time an Appendix H listing could come into force, sufficient time would have elapsed for good professional pharmacy practice to be well established. • XXXXXXXXX drew the Committee’s attention to the fact that obesity has been recognised as major health problem, and has been strongly linked to type 2 diabetes, which is one of the six National Health Priority Areas. Therefore, knowledge of the availability of a product that is indicated for obesity should strengthen the potential public health benefit. Members noted that XXXXXXXXX commented that should branded advertising of orlistat be permitted, and even if the advertisements themselves were judged to be balanced and thereby approved, the main challenge for pharmacists would likely be in gaining the consumer’s understanding for the requirement of the pharmacist to conduct a thorough risk-based assessment to determine whether or not supply of the product would be appropriate for the individual. While it would be impossible to predict the effect brand advertising of orlistat would have on the nature and volume of in-pharmacy requests, the challenge referred to could indeed be compounded by a likely increase in the volume of product requests.

The Committee noted that the NDPSC evaluator for this submission had emphasised that, in light of the requirements of Section 4 (“Principles”) of the Therapeutic Goods Advertising Code (TGAC) for Advertising item 4.1.2:

“An advertisement for therapeutic goods must not:

(a) Be likely to arouse unwarranted and unrealistic expectations of product effectiveness” and

(c) Mislead directly or by implication or through emphasis, comparisons, contrasts or omissions” (evaluator’s emphasis)

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the place of advertising to better inform the community is reasonable, providing any negative aspects of the advertised product are also presented in a balanced fashion. Thus, the evaluator supported the proposal to include orlistat in Appendix H with the proviso that reference to the modest efficacy and reduction of efficacy long-term seen in the clinical trial setting and potential side effects of orlistat need to be presented in any advertising for XXXXXXXXX under the rubric of balanced, informed and non- misleading advertising. The evaluator suggested statements such as the following to be made in any advertising for XXXXXXXXX: “Orlistat may only lead to minor weight loss in some people”, “Some people may experience side effects with orlistat particularly if diet is not adhered to” and “People may require vitamin replacement during orlistat therapy.”

Given the proposed conditions for an Appendix H listing of orlistat, the Committee acknowledged that the safeguard for branded advertising of XXXXXXXXX would be the pre-approval scheme delegated to the XXXXXXXXX for broadcast and mainstream print media advertisements. Members understood that the ASMI would assess the advertisement only for compliance with the TGAC and not for any other conditions imposed by the NDPSC. Since there appeared to be no other mechanisms that would guarantee that the recommended conditions relating to the modest efficacy and reduction of efficacy with long-term use and potential side effects of orlistat could be presented in all XXXXXXXXX advertising campaigns, members were concerned that branded advertising of XXXXXXXXX could likely provoke unwarranted and unrealistic expectations and thus misleading consumers through omissions of this information. Members therefore agreed that XXXXXXXXX was not suitable for branded advertising at this time.

OUTCOME

The Committee did not support the inclusion of orlistat in Appendix H of the SUSDP. The Committee noted the available data in the clinical trials setting using orlistat for weight loss resulted in modest efficacy and reduced long-term efficacy. Members were concerned that omission of this information in advertising campaigns could potentially create a consumer demand based on unrealistic expectations of the product’s effectiveness.

14.2.2 REQUIRED ADVISORY STATEMENTS FOR MEDICINE LABELS

PURPOSE

The Committee considered the proposed consequential amendments to the SUSDP for consistency with the Required Advisory Statements for Medicine Labels (RASML).

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BACKGROUND

The warning statements and safety directions related to human medicines in the SUSDP Appendix F, Part 3 and “reverse schedule” entries (substances required to carry mandatory warning statements as a condition for exemption from scheduling) have been transferred, without alteration, to a new document, the RASML. The RASML has been given legal effect in relation to medicines via the Therapeutic Goods Order 69 (TGO 69 as amended by TGO 69A – effective 1 July 2004), which requires medicines to include statements in accordance with the provisions of the RASML. The RASML also provides a one-year transition period for existing products and takes full effect on 1 July 2005.

DISCUSSION

The Committee noted the paper prepared by the OTC Medicines Section proposing the following consequential amendments to the human medicine entries in the SUSDP to maintain consistency between the RASML and the SUSDP:

• The inclusion of a definition of the RASML in Part 1, Interpretation section of the SUSDP. This definition is identical to that included in the Therapeutic Goods Regulations and would allow reference to the current document, without the need for amending the definition each time the RASML is amended; • The amendment of reverse schedule entries to remove any reference to the mandatory label warnings and inclusion of a reference to compliance with the RASML; • The amendment of Appendix F, Part 3 to remove entries relating to human medicines. The Committee recalled that members at the October 2004 meeting highlighted the need to retain warning statements for substances other than human therapeutic goods, eg. domestic chemicals and cosmetics, to maintain the current regulatory provisions for such substances. Furthermore, members expressed concern over the adequacy of the transition period and whether the RASML would apply to sole traders. In this regard, members were advised of the following:

• The RASML is already in effect from 1 July 2004 and that it is currently in a transition phase which ends on 1 July 2005. Members were also informed that the RASML is enforceable under the TGO 69 as amended by TGO 69A which is a standard applying to all human medicines under Section 10 of the Therapeutic Goods Act (the Act). Therefore, all medicines regulated under the Act must comply with the RASML. These include all medicines supplied by companies and non-corporate entities, for example sole traders and others like partnerships, where medicines are supplied across the states or national borders as prescribed under Section 6 of the Act. Members were advised that this also applies to non-corporate entities trading only within either Victoria or NSW in which complementary legislation requiring compliance with the Act had already been passed. Failure to comply with an applicable standard under the Act is a breach of the standard conditions of

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listing/registration and the product can be cancelled or recalled, thus leaving non- corporate entities that only trade within their local State/Territory. • With respect to interim arrangements for non-corporate entities including sole traders that only trade within their home State/Territory, members were advised that the labelling requirements in the SUSDP, not the RASML, would still apply as the entries in Appendix F, Part 3 and the ‘reverse scheduling’ provisions specified in the Schedules for human medicines would be retained until the Joint Agency became operational, unless the RASML had been given effect through State and Territory legislation, as in the case for NSW and Victoria. The Committee also noted the proposed amendments to reverse schedule entries that rely on the inclusion of mandatory warning statements on the product labels for exclusion from the operation of the SUSDP. In each case, the amendment removes the wording of the warning statement requirement, and replaces it with a requirement that labels comply with the RASML. Details of the proposed amended entries are included below. The Committee also noted that the entries in the RASML exactly reflect the current SUSDP requirements.

Members noted that a query was raised by a member in relation to the proposed amendments of the reverse schedule entries for fluoride on whether the draft entries also included products for non-therapeutic use. The Committee agreed that the draft revised entries for fluorides need careful and thorough consideration and should be distributed to members for review before formally considering the matter at the June 2005 meeting.

OUTCOME

The Committee agreed that there was a need to retain the Appendix F, Part 3 entries for human therapeutic use until the Joint Agency commences operation. Additionally, certain ‘reverse scheduling’ provisions specified in the Schedules for substances other than human therapeutic goods were also retained. The Committee also agreed to foreshadow the proposed amendments to the SUSDP for consideration at the June 2005 meeting.

FORESHADOWED DECISION (for consideration at the June 2005 meeting)

Interpretation, Part 1 – New entry

“Required Advisory Statements for Medicine Labels” means the document of that name published by the Therapeutic Goods Administration on 1 July 2004, as in force from time to time. Appendix F – Amendment

APPENDIX F WARNING STATEMENTS AND GENERAL SAFETY DIRECTIONS FOR POISONS – amend entry to read:

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APPENDIX F WARNING STATEMENTS AND GENERAL SAFETY DIRECTIONS FOR POISONS

[other than agricultural and veterinary chemicals (including pesticides) registered by the Australian Pesticides and Veterinary Medicines Authority and medicines for human use when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels]

Schedule 2 – Amendments

ASPIRIN – amend entry to read:

ASPIRIN except:

(a) when included in Schedule 4, 5 or 6;

(b) in individually wrapped powders or sachets of granules each containing 650 mg or less of aspirin as the only therapeutically active constituent other than an effervescent agent when:

(i) enclosed in a primary pack that contains 12 or less such powders or sachets of granules; and

(ii) the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(c) in tablets or capsules each containing no other therapeutically active constituent other than an effervescent agent when:

(i) packed in blister or strip packaging or in a container with a child resistant closure;

(ii) in a primary pack of not more than 25 tablets or capsules, each containing 325 mg or less of aspirin, or in a primary pack of not more than 16 tablets or capsules, each containing 500 mg or less of aspirin; and

(iii) the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

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(d) in tablets or capsules each containing no other therapeutically active constituent other than an effervescent agent when:

(i) packed in blister or strip packaging or in a container with a child-resistant closure;

(ii) in a primary pack containing 100 or less tablets or capsules, each containing 100 mg or less of aspirin when packed and labelled for the prevention of cardiovascular disease or for the inhibition of platelet aggregation; and

(iii) the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

FLUORIDES – amend entry to read:

FLUORIDES for human use (except in preparations containing 15 mg/kg or 15 mg/L or less of fluoride ion):

(a) as sodium fluoride, in preparations for ingestion containing 2.2 mg or less of sodium fluoride per dosage unit; or

(b) in preparations for topical use containing 2.5 per cent or less of fluoride ion except:

(i) pastes, powders or gels for the cleaning of teeth, included in Schedule 3;

(ii) pastes, powders or gels for the cleaning of teeth, containing 1000 mg/kg or less of fluoride ion;

(iii) other dental hygiene products, that are therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total fluoride, fitted with a child-resistant closure, when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels; or

(iv) other dental hygiene products, that are not therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total fluoride, fitted with a

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child-resistant closure and labelled with warnings to the following effect:

(A) Do not swallow; and

(B) Do not use [this product/name of product] in children six years of age or less.

IBUPROFEN – amend entry to read:

IBUPROFEN in preparations for oral use when labelled with a recommended daily dose of 1200 mg or less of ibuprofen:

(a) in liquid preparations when sold in the manufacturer’s original pack containing 4 grams or less of ibuprofen; or

(b) in divided preparations, each containing 200 mg or less of ibuprofen, in packs of not more than 100 dosage units except when:

(i) as the only therapeutically active constituent other than an effervescent agent;

(ii) packed in blister or strip packaging or in a container with a child-resistant closure;

(iii) in a primary pack containing not more than 25 dosage units; and

(iv) the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

PARACETAMOL – amend entry to read:

PARACETAMOL for therapeutic use except:

(a) when included in Schedule 4;

(b) in individually wrapped powders or sachets of granules each containing 1000 mg or less of paracetamol as the only therapeutically active constituent other than effervescent agents when:

(i) enclosed in a primary pack that contains not more than 12 such powders or sachets of granules; and

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 119

(ii) the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels; or

(c) in tablets or capsules each containing each containing 500 mg or less of paracetamol as the only therapeutically active constituent other than effervescent agents when:

(i) packed in blister or strip packaging or in a container with a child-resistant closure; and

(ii) in a primary pack of not more than 25 tablets or capsules; and

(iii) the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

PYRITHIONE ZINC – amend entry to read:

PYRITHIONE ZINC for human therapeutic use except:

(a) in semi-solid hair preparations; or

(b) in shampoos containing 2 per cent or less of pyrithione zinc when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

SILVER – amend entry to read:

SILVER for therapeutic use except:

(a) in chewing gum containing 5 per cent or less of silver per dosage unit when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in solutions for human oral use containing 0.3 per cent or less of silver when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels; or

(c) in other preparations containing 1 per cent or less of silver.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 120

Schedule 4 – Amendments

FLUORIDES – amend entry to read:

FLUORIDES in preparations for human use except:

(a) when included in Schedule 2 or 3;

(b) in pastes, powders or gels for the cleaning of teeth, containing 1000 mg/kg or less of fluoride ion;

(c) in other dental hygiene products, that are therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total fluoride, fitted with a child-resistant closure, when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(d) in other dental hygiene products, that are not therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total fluoride, fitted with a child-resistant closure and labelled with warnings to the following effect:

(A) Do not swallow; and

(B) Do not use [this product/name of product] in children six years of age or less; or

(e) in other preparations containing 15 mg/kg or 15 mg/L or less of fluoride ion.

PIPER METHYSTICUM – amend entry to read:

PIPER METHYSTICUM (Kava) in preparations for human use except:

(a) in preparations for oral use containing dried whole or peeled rhizome or containing aqueous dispersions or aqueous extracts of whole or peeled rhizome when labelled with a recommended daily dose of 250 mg or less of kavalactones:

(i) containing more than 25 mg of kavalactones per dose, when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 121

(ii) in tablet or capsule form containing 125 mg or less of kavalactones per tablet or capsule; or

(iii) in the form of a teabag when the amount of dried whole or peeled rhizome does not exceed 3 g;

(b) in topical preparations for use on the rectum, vagina or throat containing dried whole or peeled rhizome or containing aqueous dispersions or aqueous extracts of whole or peeled rhizome; or

(c) in dermal preparations.

PYRIDOXINE, PYRIDOXAL or PYRIDOXAMINE – amend entry to read:

PYRIDOXINE, PYRIDOXAL or PYRIDOXAMINE for human therapeutic use except:

(a) in oral preparations containing 200 mg or less but more than 50 mg of pyridoxine, pyridoxal or pyridoxamine per recommended daily dose except when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels; or

(b) in oral preparations containing less than 50 mg of pyridoxine, pyridoxal or pyridoxamine per recommended daily dose

VITAMIN A – amend entry to read:

VITAMIN A for human therapeutic or cosmetic use except:

(a) in preparations for topical use containing 1 per cent or less of vitamin A;

(b) in preparations for internal use, containing 100 IU or less of vitamin A per dosage unit of a divided preparation, or 100 IU or less of vitamin A per gram of an undivided preparation; or

(c) in other preparations for internal use when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

ZINC COMPOUNDS – amend entry to read:

ZINC COMPOUNDS for human internal use except:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 122

(a) in preparations with a recommended daily dose of 25 mg or less of zinc; or

(b) in preparations with a recommended daily dose of more than 25 mg but mot more than 50 mg of zinc when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

Schedule 5 – Amendments

ANISE OIL – amend entry to read:

ANISE OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 50 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 50 mL or less fitted with a restricted flow insert, and labelled with the warning:

KEEP OUT OF REACH OF CHILDREN; or

(c) in preparations containing 50 per cent or less of anise oil.

BASIL OIL – amend entry to read:

BASIL OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warning:

KEEP OUT OF REACH OF CHILDREN; or

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 123

(c) in preparations containing 5 per cent or less of methyl chavicol.

BERGAMOT OIL – amend entry to read:

BERGAMOT OIL except:

(a) when steam distilled or rectified;

(b) in preparations for internal use;

(c) in preparations containing 0.4 per cent or less of bergamot oil;

(d) in soaps or bath or shower gels that are washed off the skin;

(e) in preparations other than medicines for human therapeutic use, when packed in containers labelled with the statement:

Application to the skin may increase sensitivity to sunlight; or

(f) in medicines for human therapeutic use, when packed in containers and the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

CAMPHOR – amend entry to read:

CAMPHOR as a natural component in essential oils containing 10 per cent or less of camphor except:

(a) in medicines for human therapeutic use, in essential oils packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, in essential oils packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(c) in rosemary oil, sage oil (Spanish), or lavindin oils; or

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 124

(d) in preparations containing 2.5 per cent or less of camphor.

DIETHYLTOLUAMIDE (DEET) – amend entry to read:

DIETHYLTOLUAMIDE (DEET) except:

(a) in medicines for human therapeutic use containing 20 per cent or less of diethyltoluamide, when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations for human use, other than medicines, containing 20 per cent or less of diethyltoluamide, when labelled with the warning statement:

WARNING: May be dangerous, particularly to children, if you use large amounts on the skin, clothes or bedding or on large areas of the body, especially if you keep using it for a long time; or

(c) in preparations other than for human use containing 20 per cent or less of diethyltoluamide.

FLUORIDES – amend entry to read:

FLUORIDES in preparations containing 3 per cent or less of fluoride ion except:

(a) when included in Schedule 2, 3 or 4;

(b) in pastes, powders or gels for the cleaning of teeth, containing 1000 mg/kg or less of fluoride ion;

(c) in other dental hygiene products, that are therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total fluoride, fitted with a child-resistant closure, when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(d) in other dental hygiene products, that are not therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total fluoride, fitted with a child-resistant closure and labelled with warnings to the following effect:

(A) Do not swallow; and

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 125

(B) Do not use [this product/name of product] in children 6 years of age or less; or

(e) in other preparations containing 15 mg/kg or 15 mg/L or less of fluoride ion.

LEMON OIL – amend entry to read:

LEMON OIL except:

(a) when steam distilled or rectified;

(b) in preparations for internal use;

(c) in preparations containing 0.05 per cent or less of lemon oil;

(d) in soaps or bath or shower gels that are washed off the skin;

(e) in preparations other than medicines for human therapeutic use, when packed in containers labelled with the statement:

Application to the skin may increase sensitivity to sunlight; or

(f) in medicines for human therapeutic use, when packed in containers and the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

LIME OIL – amend entry to read:

LIME OIL except:

(a) when steam distilled or rectified;

(b) in preparations for internal use;

(c) in preparations containing 0.5 per cent or less of lime oil;

(d) in soaps or bath or shower gels that are washed off the skin;

(e) in preparations other than medicines for human therapeutic use, when packed in containers labelled with the statement:

Application to the skin may increase sensitivity to sunlight; or

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 126

(f) in medicines for human therapeutic use, when packed in containers and the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

MARJORAM OIL – amend entry to read:

MARJORAM OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 50 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 50 mL or less fitted with a restricted flow insert, and labelled with the warning:

KEEP OUT OF REACH OF CHILDREN; or

(c) in preparations containing 50 per cent or less of marjoram oil.

NUTMEG OIL – amend entry to read:

NUTMEG OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warning:

KEEP OUT OF REACH OF CHILDREN; or

(c) in preparations containing 50 per cent or less of nutmeg oil.

ORANGE OIL – amend entry to read:

ORANGE OIL except:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 127

(a) when steam distilled or rectified;

(b) in preparations for internal use;

(c) in preparations containing 1.4 per cent or less of orange oil;

(d) in soaps or bath or shower gels that are washed off the skin;

(e) in preparations other than medicines for human therapeutic use, when packed in containers labelled with the statement:

Application to the skin may increase sensitivity to sunlight; or

(f) in medicines for human therapeutic use, when packed in containers and the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels.

STAR ANISE OIL – amend entry to read:

STAR ANISE OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 50 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 50 mL or less fitted with a restricted flow insert, and labelled with the warning:

KEEP OUT OF REACH OF CHILDREN; or

(b) in preparations containing 50 per cent or less of star anise oil.

THYME OIL – amend entry to read:

THYME OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and when the label on the

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 128

primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert, and labelled with the warning:

KEEP OUT OF REACH OF CHILDREN; or

(c) in preparations containing 50 per cent or less of thyme oil.

Schedule 6 – Amendments

AZADIRACHTA INDICA (Neem) – amend entry to read:

(†) AZADIRACHTA INDICA (Neem) including its extracts and derivatives except:

(a) when included in Schedule 5;

(b) in preparations for human internal use;

(c) debitterised neem seed oil;

(d) in preparations for human dermal therapeutic use containing cold pressed neem seed oil, when in a container fitted with a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels; or

(e) in preparations for dermal use containing 1 per cent or less of cold pressed neem seed oil.

BAY OIL – amend entry to read:

BAY OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 129

requirements of the Required Advisory Statements for Medicine Labels;

(c) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(e) in preparations containing 25 per cent or less of bay oil.

CAJUPUT OIL – amend entry to read:

CAJUPUT OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(c) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 130

NOT TO BE TAKEN;

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(e) in preparations containing 25 per cent or less of cajuput oil; or

(f) in oils containing 25 per cent or less of cajuput oil.

CAMPHOR – amend entry to read:

CAMPHOR except:

(a) when included in Schedule 4 or 5;

(b) when enclosed in an inhaler device which prevents ingestion of its contents;

(c) in solid or semi-solid preparations containing 12.5 per cent or less of camphor;

(d) in liquid preparations containing 2.5 per cent or less of camphor;

(e) in essential oils when the camphor is present as a natural component of the oil:

(i) in medicines for human therapeutic use, packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(ii) in medicines for human therapeutic use, packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child- resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 131

(iii) in essential oils other than medicines for human therapeutic use, packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(iv) in essential oils other than medicines for human therapeutic use, packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(f) in rosemary oil, sage oil (Spanish), or lavindin oil as such.

CINEOLE – amend entry to read:

CINEOLE except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(c) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 132

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(e) in preparations containing 25 per cent or less of cineole;

(f) in oils containing 25 per cent or less of cineole; or

(g) in rosemary oil or camphor oil (white).

CINNAMON LEAF OIL – amend entry to read:

CINNAMON LEAF OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(c) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 133

NOT TO BE TAKEN; or

(e) in preparations containing 25 per cent or less of cinnamon leaf oil.

CLOVE OIL – amend entry to read:

CLOVE OIL except:

(a) when included in Schedule 5;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(c) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(e) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(f) in preparations containing 25 per cent or less of clove oil.

EUCALYPTUS OIL – amend entry to read:

EUCALYPTUS OIL except:

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 134

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(c) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(e) in preparations containing 25 per cent or less of eucalyptus oil.

EUGENOL – amend entry to read:

EUGENOL except:

(a) when included in Schedule 5;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 135

(c) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(e) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(f) in preparations containing 25 per cent or less of eugenol.

FLUORIDES – amend entry to read:

FLUORIDES except:

(a) when included in Schedule 2, 3 ,4 or 5;

(b) in pastes, powders or gels for the cleaning of teeth, containing 1000 mg/kg or less of fluoride ion;

(c) in other dental hygiene products, that are therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total fluoride, fitted with a child-resistant closure, when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(d) in other dental hygiene products, that are not therapeutic goods, containing 220 mg/kg or 220 mg/L or less of fluoride ion, in packs containing not more than 120 mg total

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 136

fluoride, fitted with a child-resistant closure and labelled with warnings to the following effect:

(A) Do not swallow; and

(B) Do not use [this product/name of product] in children six years of age or less; or

(e) in other preparations containing 15 mg/kg or 15 mg/L or less of fluoride ion.

MELALEUCA OIL (Tea tree oil) – amend entry to read:

MELALEUCA OIL (Tea tree oil) except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(c) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN;

(d) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 25 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 137

(e) in preparations containing 25 per cent or less of melaleuca oil.

PENNYROYAL OIL – amend entry to read:

PENNYROYAL OIL except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(c) in preparations containing 4 per cent or less of d-pulgone.

PYRITHIONE ZINC – amend entry to read:

PYRITHIONE ZINC except:

(a) when included in Schedule 2;

(b) in semi-solid hair preparations;

(c) in shampoos containing 2 per cent or less of pyrithione zinc when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels; or

(d) when immobilised in solid preparations containing 0.5 per cent or less of pyrithione zinc.

SAGE OIL (Dalmatian) – amend entry to read:

SAGE OIL (Dalmatian) except:

(a) in medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 138

with a restricted flow insert and a child-resistant closure and when the label on the primary pack complies with the requirements of the Required Advisory Statements for Medicine Labels;

(b) in preparations other than medicines for human therapeutic use, when packed in containers having a nominal capacity of 15 mL or less fitted with a restricted flow insert and a child-resistant closure and labelled with the warnings:

KEEP OUT OF REACH OF CHILDREN; and

NOT TO BE TAKEN; or

(c) in preparations containing 4 per cent or less of thujone.

15. MATTERS REFERRED BY THE AUSTRALIAN DRUG EVALUATION COMMITTEE (ADEC)

15.1 NEW SUBSTANCES

15.1.1 MOXONIDINE

DECISION 2005/43 - 16

The Committee agreed to include moxonidine in Schedule 4 of the SUSDP on the grounds that the condition being treated necessitates appropriate medical diagnosis and the safe use of this medicine requires patient management and monitoring by a medical professional.

Schedule 4 – New entry

MOXONIDINE.

15.1.2 EFALIZUMAB

DECISION 2005/43 - 17

The Committee agreed to include efalizumab in Schedule 4 of the SUSDP on the grounds that the condition being treated necessitates appropriate medical diagnosis and the safe use of this medicine requires patient management and monitoring by a medical professional. The inclusion of efalizumab in Schedule 4 harmonises the scheduling of this substance with New Zealand.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 139

Schedule 4 - New entry

EFALIZUMAB.

15.1.4 EMTRICITABINE

DECISION 2005/43 - 18

The Committee agreed to include emtricitabine in Schedule 4 of the SUSDP on the grounds that the condition being treated necessitates appropriate medical diagnosis and the safe use of this medicine requires patient management and monitoring by a medical professional. Furthermore, the inclusion of emtricitabine in Schedule 4 harmonises with New Zealand.

Schedule 4 - New entry

EMTRICITABINE.

23. AMENDMENTS TO THE SUSDP

23.1 EDITORIAL CHANGES AND ERRATA

23.1.1 HYOSCYAMUS NIGER

PURPOSE

The Committee considered erratum to the SUSDP regarding Hyoscyamus niger.

BACKGROUND

The February 2004 NDPSC Meeting agreed to an amendment to the Schedule 2 entry for Hyoscyamus niger to exempt preparations containing 30 micrograms or less of total solanaceous alkaloids from the requirements of scheduling.

The October 2004 NDPSC Meeting considered a transcription error that was detected by a Committee member. The Committee confirmed that the Schedule 2 entry for Hyoscyamus niger should have read “in divided preparations containing 0.3 mg of total solanaceous alkaloids or less”....and not 0.03 mg of total solanaceous alkaloids. The Committee agreed to editorially amend the Schedule 2 entry for Hyoscyamus niger for inclusion in SUSDP 19/2.

DISCUSSION

The Members noted that XXXXXXXXX had advised the Secretariat that the exception statement had been inadvertently omitted from the amended Schedule 2 entry included in SUSDP 19/2.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 140

DECISION 2005/43 - 19

The Committee agreed to correct the Schedule 2 entry for Hyoscyamus niger for inclusion in SUSDP 19/3.

Schedule 2 - Amendment

HYOSCYAMUS NIGER – amend to read:

HYOSCYAMUS NIGER for oral use:

(a) in undivided preparations containing 0.03 per cent or less of total solanaceous alkaloids when labelled with a dose of 0.3 mg or less of total solanaceous alkaloids and a recommended daily dose of 1.2 mg or less of total solanaceous alkaloids; or

(b) in divided preparations containing 0.3 mg of total solanaceous alkaloids or less per dosage unit when labelled with a recommended daily dose of 1.2 mg or less of total solanaceous alkaloids.

except in a pack containing 0.03 mg or less of total solanaceous alkaloids.

23.1.2 SELENIUM

PURPOSE

The Committee considered an erratum in the SUSDP regarding selenium.

BACKGROUND

The Committee last considered the Schedule 6 entry for selenium at the February 2001 meeting where the entry was amended to include barium selenate injections. The February 2002 meeting considered a transcription error where clause (e) of the old entry dealing with intraruminal-bolus preparations was omitted from the new S6 entry.

During the redrafting of the S6 entry for selenium at the February 2001 meeting, the phrase “or horse feed supplement” was omitted. This omission was not corrected at the February 2002 meeting.

DISCUSSION

The APVMA recently highlighted that the reference to “horse feed supplement” has been inadvertently omitted from the Schedule 6 entry for selenium.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 141

DECISION 2005/43 - 20

The Committee agreed to correct the Schedule 6 entry for selenium for inclusion in SUSDP 19/3.

Schedule 6 – Amendment

SELENIUM:

(a) in preparations containing 2.5 per cent or less of selenium when packed and labelled:

(i) for the blueing of gun barrels;

(ii) for photographic purposes; or

(iii) for the colouring of lead or lead alloys;

(b) in coated granules containing 1 per cent or less of selenium for application to pasture except in fertilisers containing 200 g/tonne or less of selenium; or

(c) for the treatment of animals:

(i) in a drench, injection, paste, stocklick, vaccine or horse feed supplement containing 0.5 per cent or less of selenium;

(ii) in animal feed premixes containing 2 per cent or less of selenium for the preparation of feeds containing 1 g/tonne or less of selenium;

(iii) in controlled release bolus preparations containing 25 mg or less of selenium with a release rate not greater than 0.25 mg/ day; or

(iv) as barium selenate in preparations for injection containing 5 per cent or less of selenium.

23.1.3 ASPIRIN – FOR INFORMATION

PURPOSE

The Committee noted the inclusion of a minor editorial amendment to the SUSDP 19 Amendment 2 regarding aspirin.

National Drugs and Poisons Schedule Committee Record of Reasons of Meeting 43 – February 2005 142

BACKGROUND

XXXXXXXXX drew the Secretariat’s attention to a transcription error in the Appendix F, Part 3 entry for aspirin in the SUSDP 19.

The NDPSC Secretariat confirmed that warning statement (WS) 37 required for aspirin in Appendix F, Part 3 (SUSDP 18/3) was erroneously transcribed to read as WS 107 during the consolidation of SUSDP 19.

OUTCOME

The Committee noted that the following editorial amendment was included in SUSDP No.19 Amendment No.2.

Appendix F, Part 3 Warning Statements Aspirin

(a) for inhibition of platelet aggregation. 36

(b) in sustained release preparations containing 650 mg or more of aspirin 36

(c) except as above

(i) 37 and 38 and

(ii) 34 or 35 or 36 (permitted until 30 April 2005) or

(iii) 37, 101, 102 and 103 (mandatory from 1 May 2005).