required advisory statements for medicine labels updates ... · (excluding atropine methonitrate),...

Required Advisory Statements for Medicine Labels updates TGA response to submissions

Version 3.0, April 2012

Histor

ical

doc

umen

t

Therapeutic Goods Administration

Copyright © Commonwealth of Australia 2011 This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to <[email protected]>.

Required Advisory Statements for Medicine Labels updates: TGA response to submissions, V2.0 November 2011

Page i

About the Therapeutic Goods Administration (TGA) · The TGA is a division of the Australian Government Department of Health and Ageing, and is

responsible for regulating medicines and medical devices.

· TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance), when necessary.

· The work of the TGA is based on applying scientific and clinical expertise to decision-making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices.

· The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action.

· To report a problem with a medicine or medical device, please see the information on the TGA website.

Histor

ical

doc

umen

t

mailto:[email protected]�



Page 1 of 51

Version history

Version Description of change Author Effective date

V1.0 First version OTCME 7 October 2011

V2.0 The following summarises the amendments to this document: page 1 - Inclusion of version history table

page 4 – Inclusion of the statement beginning with “The process of amending ......” page 5 – Inclusion of the statement under the subtitle Next Steps beginning “It is a requirement .....”

page 16 – Replace “lactation” with “breastfeeding”

page 18 – Aspirin- Correction of outcome 1

page 20 – Chlorhexidine – Correction of outcome 2

page 23 – Fluorides – Correction of outcome 2

page 28 – NSAIDS - Correction of outcome 1

page 29 – Vasoconstrictor eye drops – Deletion from TGA Consideration, the sentence “However, advisory statement 209 will still apply to other vasoconstrictor eye drops” page 32 – Inclusion of the advisory Statement 192 page 33 – Revised advisory statement 76 - Correction of advisory statement in TGA consideration page 35 – Inclusion of TGA consideration of advisory statement 192 page 38 – Advisory statement 204 - Correction of outcome 1 Page 41 – Advisory statement 211 - Correction of outcome 1 page 44 – Advisory statement 225 – Correction of outcome 1 When reviewing this document, typographical and grammatical errors were corrected

OTCME 24 November 2011

Histor

ical

doc

umen

t



Page 2 of 51

V3.0 page 7 – Advisory statement 180 – Correction of statement by replacing “condition” with “[condition/insert type of condition]” page 8 -

· Advisory statement 193 - Correction of statement by addition of the word “phenylalanine” and deletion of the sentence “(or words to that effect)”

· Advisory statement 196 - Correction in the deletion of the sentence “(or words to that effect)”

· Advisory statement 199 – Correction in the deletion of the sentence “(or words that that effect)”

Page 18 - Correction of outcome 1 by deleting ‘listed’ from ‘listed medicines’ Version history – page number has been amended to reflect the correct pages as a result of changes in version 3.0

OTCME 21 May 2012

Histor

ical

doc

umen

t



Page 3 of 51

Contents RASML Update 5 _______________________________________________________________ 4

RASML Update 6 _______________________________________________________________ 4

Outcome of the public consultation period _______________________________ 5

Changes to the final document ______________________________________________ 5

Next Steps _______________________________________________________________________ 5

Abbreviations __________________________________________________________________ 6

Advisory statements __________________________________________________________ 7

Section 1: Application of advisory statement (s) to the medicine __ 12

Section 2: The wording of the advisory statement(s) _________________ 32

Section 3 – General comments ____________________________________________ 48

Histor

ical

doc

umen

t



Page 4 of 51

The TGA is in the process of revising and updating the Required Advisory Statements for Medicine Labels (Edition 1, including update 4) dated September 2008 (RASML). The proposed changes were made in consultation with a working group consisting of the Office of Complementary Medicines and OTC Medicines Evaluation section. Following public consultation in July 2009 and February 2011, the submissions from stakeholders as well as TGA response to the submissions are published below.

RASML Update 5 The TGA released the proposed RASML (Update 5) for stakeholder and public consultation on 16 July 2009. In addition to the letters seeking specific comment from the main industry associations, the TGA also promulgated the proposed RASML document on the TGA website. The public consultation closed on 17 August 2009.

Submissions were received from the following industry group, organisations and individuals:

1. Pharmaceutical Society of Australia 2. Pharmacy Guild of Australia 3. Complementary Healthcare Council of Australia 4. Australian Self Medication Industry 5. Pharmaceutical Council of Western Australia 6. Pfizer Australia 7. Bayer Australia Limited 8. A stakeholder 9. A sponsor

RASML Update 6 The TGA released the proposed RASML (Update 6) on the TGA website for stakeholder and public consultation on 18 February 2011. In addition letters were also sent out seeking specific comment from the main industry associations. After initial feedback from stakeholders, additional explanatory notes were provided on the TGA website and the consultation period was extended to 13 May 2011. Submissions were received from the following industry group, organisations and individuals:

1. Roche Products Pty Ltd 2. Pharmaceutical Society of Australia 3. Bayer Australia Limited 4. ACCORD 5. Pharmacy Guild of Australia 6. Apotex Pty Ltd 7. Colgate-Palmolive (Australia) Pty Limited 8. Consumers Health Forum 9. Complementary Health Council

The process of amending the Therapeutic Goods Order No. 69 - General requirements for labels for medicines to include reference to the updated RASML is underway. In the meantime, the RASML Edition 1 including update 4 (dated September 2008) remains the current version which sponsors should continue to refer to.

Histor

ical

doc

umen

t

http://www.comlaw.gov.au/Details/F2009C00264�

http://www.comlaw.gov.au/Details/F2009C00264�



Page 5 of 51

10. Dr Ken Harvey 11. Australian Self Medication Industry 12. A sponsor 13. A sponsor

Outcome of the public consultation period All public submissions to RASML 5 update and RASML 6 update have been considered by a working group within the Office of Complementary Medicines and OTC medicines evaluation. The issues and TGA consideration have been tabulated and are outline in 3 sections:

· Section 1: Application of advisory statement(s) to the medicine

· Section 2: The wording of the advisory statements

· Section 3: General comments

Changes to the final document Changes made to the draft published previously as a consultation include editorial changes designed to improve clarity and consistency. However, a number of significant changes have been made in response to comments and suggestions made from those submissions. It should also be noted that as a result of changes made in response to the feedback, the number denoting the advisory statements will be amended in the final document and will not reflect the numbering order as set out in the consultation document.

Next Steps It is a requirement of Australian Government agencies that a Regulatory Impact Statement (RIS) is prepared for all decisions made by the Australian Government and its agencies that are likely to have a regulatory impact on business or the not-for-profit sector, unless that impact is of a minor or machinery nature and does not substantially alter existing arrangements.

The primary role of the RIS is to improve government decision-making processes by ensuring that all relevant information is presented to the decision maker.

The Office of Best Practice Regulation in the Department of Finance and Deregulation is responsible for the quality control of RISs and must clear the RIS before it is submitted to the decision maker.

Histor

ical

doc

umen

t



Page 6 of 51

Abbreviations

ACCM Advisory Committee on Complementary Medicines (previously known as CMEC)

ACCS Advisory Committee on Chemical Scheduling

ACMS Advisory Committee on Medicine Scheduling (previously known as NDPSC)

ACNM Advisory Committee on Non-prescription Medicines (previously known as MEC)

ACSOM Advisory Committee on Safety of Medicines (previously known as ADRAC)

ADRAC Adverse Drug Reaction Advisory Committee

ARGOM Australian Regulatory Guideline for Over-the-counter Medicines

ARTG Australian Register of Therapeutic Goods

CMEC Complementary Medicines Evaluation Committee

ELF Electronic Listing Facility

OTC Over-the-counter

MEC Medicines Evaluation Committee

NDPSC National Drugs and Poisons Scheduling Committee

RASML Required Advisory Statement for Medicine Labels

SUSMP Standard Uniform Scheduling for Medicines and Poisons

SUSDP Standard Uniform Scheduling of Drugs and Poisons

TGA Therapeutic Goods Administration.

Histor

ical

doc

umen

t


Required Advisory Statements for Medicines Labels updates: TGA response to submissions, V1.0 October 2011

Page 7 of 51

Advisory statements

No Advisory statement Medicines to which the statement will apply

177 See a doctor before use if you are diabetic. Fluconazole

178 WARNING – Stop taking this medication if you experience tingling, burning or numbness and see your healthcare practitioner as soon as possible.

Pyridoxal, Pyridoxine, Pyridoxamine

179 WARNING – Stop taking this medication if you experience tingling, burning or numbness and see your healthcare practitioner as soon as possible. Contains vitamin B6.

Pyridoxal, Pyridoxine, Pyridoxamine

180 If the [condition/insert type of condition] persists after two days of treatment, seek medical advice as soon as possible.

Anticholinergics, Atropa Belladona, Atropine Compounds, (excluding atropine methonitrate), Datura Spp, Hyoscine compounds, Hyoscyamine compounds, Hyoscamus niger

181 Chitosan should be taken at least one hour after any other medication as it may reduce the effect of other medication.

Chitosan

182 Do not take powder alone. Mix with food or fluid. Chitosan

183 Do not exceed the stated dose except on medical advice. If you have had a baby with a neural tube defect/spina bifida, seek specific medical advice.

Folic acid

184 Drink plenty of water. Hydroxyanthracene derivatives

185 Prolonged use may cause serious bowel problems. Hydroxyanthracene derivatives

186 Do not use when abdominal pain, nausea or vomiting are present, or if you develop diarrhoea. If you are pregnant or breast feeding, seek the advice of a healthcare professional before taking this product.

Hydroxyanthracene derivatives

187 This product contains [name of the herb(s) or the chemical component(s)]. Hydroxyanthracene derivatives

188 Not for the treatment of iron deficiency. Iron compounds

Histor

ical

doc

umen

t



Page 8 of 51


189 This product may cause photosensitization. Psoralea coryfolia

190 Should only be used for children on medical advice. Psyllium

191 There is no benefit from taking more than 3 g/day of phytosterols from all sources. Vegetable oil phytosterol esters.

192 Ask your doctor or pharmacist before use if you are dehydrated, or have diarrhoea or vomiting. Diclofenac, Flurbiprofen, Ibuprofen, Ketoprofen Mefenamic Acid, Naproxen

193 Phenylketonurics are warned that this product contains aspartame (phenylalanine) Aspartame

194 This product may make your skin more sensitive to sunlight. Alphahydroxy acids

195 Sun exposure should be limited by using a sunscreen and by wearing protective clothing. Alphahydroxy acids

196 This product contains pollen which can cause severe allergic reactions Pollen

197 Use only as directed. Potassium Chloride, Sodium Bicarbonate

198 If diarrhoea persists, seek medical advice. Potassium chloride, Sodium Bicarbonate

199 Contains [insert name of ingredient] Ethohexadiol, Pyrethrins, Wheat Dextrin

200 Do not use if you have impaired kidney function. Diclofenac, Flurbiprofen, Ibuprofen, Ketoprofen, Mefenamic acid, Naproxen, Excipients (octylbicycloheptene dicarboximide, piperonyl butoxide, pyrethrins)

201 Do not use if you have heart failure. Diclofenac, Flurbiprofen, Ibuprofen, Ketoprofen, Mefenamic aicd, Naproxen

Histor

ical

doc

umen

t



Page 9 of 51


202 Unless a doctor has told you to, do not use [this product / product name] with other medicines that you are taking regularly

Diclofenac, Ibuprofen, Indomethacin, Ketoprofen (dermal preparations)

203 Do not take hot food or drink soon after using this product because it may burn your mouth. Benzocaine, Lignocaine lozenge

204 Do not give to children under 6 years of age, unless recommended by a doctor, pharmacist or dental professional.

Benzocaine Lignocaine lozenge

205 Do not apply to large areas of the body, except on the advice of a healthcare practitioner. Amethocaine, Benzocaine, Cinchocaine, Lignocaine

206 This product is for temporary use. Antihistamine including Diphenhydramine, Doxylamine, Promethazine

207 Do not use for prolonged periods except on the advice of a doctor. Coal tar

208 See your doctor before taking this product if you have high blood pressure or heart problems or are taking antidepressant medication.

Phenylephrine, Pseudoephedrine

209 [This product/Product name] may cause sleeplessness if it is taken up to several hours before going to bed.

Phenylephrine, Pseudoephedrine

210 Do not use except on the advice of a dentist. Fluorides

211 Long term and repeated use should be avoided because darkening of the skin could occur. Hydroquinone

212 WARNING – This product contains Chlorhexidine. Severe allergic reactions can occur. Stop use if this occurs.

Chlorhexidine

213 Transient stinging or irritation may occur when using this product. If irritation persists, discontinue use. Alphahydroxy acids

214 If you have sensitive skin, test this product on a small area of skin before applying it to a large area Alphahydroxy acids

Histor

ical

doc

umen

t



Page 10 of 51


215 May be irritant to the eyes (or words to that effect) Excipients

216 Will irritate the eyes

217 If skin irritation occurs, discontinue use and seek medical advice. Amethocaine, Benzocaine, Cinchocaine, Lignocaine

218 Not recommended for use on children and infants. Alphahydroxy acids

219 If skin irritation occurs, discontinue use immediately. Povidone -Iodine

220 This product should be taken on medical or pharmacist advice. Antihistamine including Diphenhydramine, Doxylamine, Promethazine

221 This preparation is to aid sleep. Drowsiness may continue the following day. If affected do not drive or operate machinery. Avoid alcohol.

Antihistamine including Diphenhydramine, Doxylamine, Promethazine

222 Do not apply to infants under 12 months of age except on the advice of a doctor. Camphor

223 Ask your doctor or pharmacist before use if you are taking other medicines regularly. Proton pump inhibitors including Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole

224 This preparation should be used with caution on infants, small children and pregnant of lactating women.

Lindane

225 Medical advice should be sought before use. Lindane

226 Prolonged use may be harmful Vasoconstrictor eye drops including Naphazoline, Phenylephrine, and Tetrahydrozoline

227 Consult a doctor or pharmacist if using other eye products. Vasoconstrictor eye drops including Naphazoline, Phenylephrine, and Tetrahydrozoline

Histor

ical

doc

umen

t



Page 11 of 51


228 Do not use if you have glaucoma or other serious eye conditions. Vasoconstrictor eye drops including Naphazoline, Phenylephrine, and Tetrahydrozoline

229 If symptoms persist, consult a doctor. Vasoconstrictor eye drops including Naphazoline, Phenylephrine, and Tetrahydrozoline

230 Do not exceed the recommended dose. Excessive use can be harmful. Choline salicylate

Histor

ical

doc

umen

t



Page 12 of 51

Section 1: Application of advisory statement (s) to the medicine · Alphahydroxy acids (glycollic acid, lactic acid, citric acid and other fruit acids) · Anaesthetics, dermal (Amethocaine, Benzocaine, Cinchocaine, Lignocaine) · Anaesthetics, dermal (Amethocaine, Benzocaine, Lignocaine) · Anaesthetics, dermal (Cinchocaine) · Anticholinergic products (Atropa belladonna, Atropine compounds (excluding atropine methonitrate), Datura spp., Hyoscine compounds,

Hyoscyamine compounds, Hyoscyamus niger) · Aspartame · Aspirin · Chlorhexidine · Choline Salicylate · Decongestant, oral (Phenylephrine, Pseudoephedrine) · Excipients (Butylester of pvm/ma copolymer, DEA-Oleth-3 phosphate, Diethylhexyl-2,6-napthalate, Erythrulose, Ethyl butylacetyl-

aminopropionate, Stearamidopropyl PG-dimonium chloride phosphate, Stearyl dimethicone, Sucrose polycottonseedate) · Fluorides · Folic acid · Hydrolysed milk protein - alpha casozepine enriched · Hypericum Perforatum · Imidazoles ( Butoconazole, Clotrimazole, Econazole, Miconazole, Oxiconazole, Tioconazole) · Non steroidal anti-inflammatory drugs (NSAIDs) (Benzydamine, Diclofenac, Flurbiprofen, Ibuprofen, Indomethacin, Ketoprofen, Naproxen,

Mefenamic acid) · Potassium chloride · Proton pump Inhibitors (Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole) · Psyllium · Pyridoxal, Pyridoxamine, and Pyridoxine · Vasoconstrictor eye drops (Naphazoline, Phenylephrine, Tetrahydrozoline) · Clarify ‘words to the effect’ · Package Labelling

Histor

ical

doc

umen

t



Page 13 of 51

Alphahydroxy acids (glycollic acid, lactic acid, citric acid and other fruit acids)

Consultation Description of issue(s) TGA consideration

RASML Update 6 (2011)

· ACCORD and another sponsor argues that the proposed warnings are inappropriate for products containing alphahydroxy acids (AHA) in low concentrations, such as when included for their buffering capacity. Therefore the advisory statements 194 & 195 should be confined to products that contain AHAs at sufficiently high concentrations, and in formulations that are designed to remove dead skin cells. Equally, the advisory statements 213 & 214 are formulation dependent and are only appropriate for products with higher concentrations of AHAs and low pH.

· ASMI further suggests that the advisory statements be applied only when alpha hydroxy acids are included as active ingredients and specifying the indication “when used in topical products to remove dead skin cells”.

· The TGA acknowledges that low concentrations of AHAs are used as buffers in certain formulations. Therefore TGA agrees with the proposal that the advisory statements 194, 195 213 and 214 will only be applied to those topical products which include alpha hydroxy acid as active ingredients.

· However, TGA does not agree with limiting to the specific indication “to remove dead skin cells” as alpha hydroxy acid may be used to treat other conditions such as acne or melasma.

Outcome 1. Amend proposed condition for AHA from “ When in preparation for topical use” to “When used as active ingredients in preparations for topical use”

Anaesthetics, dermal (Amethocaine, Benzocaine, Cinchocaine, Lignocaine)



· Both a sponsor and ASMI point out that the advisory statement 205 is not currently required in the current Australian Regulatory Guideline for OTC Medicine (ARGOM 2003) but was newly introduced in the draft update of ARGOM which has not been finalized.

· The TGA acknowledges that advisory statement 205 is not currently required in the current ARGOM 2003. However it is consistent with current practice during evaluation of applications and reflected in the draft update of ARGOM.

Outcome 2. Retain the advisory statement 205 without amendment

Histor

ical

doc

umen

t



Page 14 of 51

Anaesthetics, dermal (Amethocaine, Benzocaine, Lignocaine)



· ASMI raises the concern that the condition proposed for the RASML entry extends the requirement to both dermal and topical use whilst the draft update of ARGOM requires the advisory statement to only apply to dermal use. Therefore, ASMI suggests rephrasing the condition to “included in Schedule 2 to the SUSMP when for dermal use and to include a separate entry for Amethocaine when excluded from the Schedule.

· ASMI points out that Lignocaine and other local anaesthetics are used in preparations containing 2% or less to help relieve mild sunburn, and as such may be used on large areas of the body. Therefore ASMI suggests that only advisory statement 217 be required for the products when excluded from the Schedules to the SUSMP.

· The TGA agrees with the suggestions put forward by ASMI.

Outcome 1. Separate the conditions and include a new entry for Amethocaine. 2. Include a new entry and condition for Benzocaine and Lignocaine:

- The amended condition “when for the purpose of exclusion from the Schedules to the SUSMP when in dermal preparations containing 2 per cent or less of total local anaesthetic substances” will only require advisory statement 217.

- The new condition “when included in Schedule 2 to the SUSMP and for dermal use” will require advisory statement 205 and 217.

Anaesthetics, dermal (Cinchocaine)



· A sponsor does not support the application of the advisory statement 205 to haemorrhoidal products, as these are used only on the rectal area and are sold with applicators for use for internal haemorrhoids. The sponsor points out that inclusion of the proposed warning on the pack would carry with it the implication that the product might be able to be used on large areas and it might possibly cause confusion for consumers.

· ASMI interprets the SUSMP entry for Cinchocaine as not being excluded from scheduling for any purpose. Therefore ASMI considers that the condition set out for

· The TGA notes the issue raised by the stakeholders with respect to confusion caused by advisory statement 205 for haemorrhoidal products. The TGA acknowledges that the condition for Cinchocaine is incorrect and accepts the suggestion put forward by ASMI to rephrase the condition

Histor

ical

doc

umen

t



Page 15 of 51


Cinchocaine is incorrect. In addition, ASMI maintains that as Cinchocaine is mainly used in haemorrhoidal products and not usually applied to a large area of the body, the advisory statement 205 should not be required.

· ASMI suggest either deleting the Cinchocaine entry or rephrase the condition to ‘included in Schedule 2 to the SUSMP when for dermal use only”

Outcome 1. Include a new entry and amend condition for Cinchocaine: - The amended condition “when included in Schedule 2 for dermal use” will require advisory statements 205 and 217 - The new condition “when for rectal use only” will only require advisory statements 217

Anticholinergic products (Atropa belladonna, Atropine compounds (excluding atropine methonitrate), Datura spp., Hyoscine compounds, Hyoscyamine compounds, Hyoscyamus niger)



· The Pharmacy Guild notes an inconsistency with other related products for diarrhoea such as Loperamide or Diphenoxylate, both of which require RASML statement 17: “Do not use beyond 48 hours or in pregnancy or lactating women except on doctor’s advice.” Products containing Diphenoxylate also contain a small amount of Atropine sulphate, which has little therapeutic significance but is added to discourage excessive self-medication. These combination products will thus require both RASML statements 17 - “Do not use beyond 48 hours or in pregnancy or lactating women except on doctor’s advice”) for Diphenoxylate, and the warning statement “If the condition persists after two days of treatment, seek medical advice as soon as possible” for Atropine. In this regard, the Guild suggests that it would be more appropriate to have consistent labelling requirements for all Over the counter (OTC) antispasmodic/antidiarrhoeal products relating to duration of treatment and use during pregnancy and lactation.

· With respect to use in pregnancy, the Guild highlights that Atropine and Hyoscine are both classified as pregnancy Category A, Loperamide is Category B3 while

· In relation to duration of use, the intent of advisory statement 17 (in part) “Do not use beyond 48 hours... except on doctor’s advice” and 180 “If the condition persists after two days of treatment, seek medical advice as soon as possible” is the same. Thus, for combination products containing Diphenoxylate and Atropine which will require both RASML statements 17 (for Diphenoxylate) and 180 (for Atropine), the products will have complied with Required Advisory Statement for Medicine Labels (RASML). This is also consistent with the section on combination statements in the RASML document which states that “Where more than one statement is required, they may be combined to form simple sentences where appropriate, provided that the intent of each of the statements is not changed and any

Histor

ical

doc

umen

t



Page 16 of 51


Diphenoxylate is Category C. Therefore the Pharmacy Guild suggests that all OTC antispasmodic/antidiarrhoeals should have the advisory statement “If the condition persists after two days of treatment, seek medical advice as soon as possible”) and that either RASML statement 15 (“Not recommended for use by pregnant or lactating women”) or a new RASML in the manner of “Do not use during pregnancy or lactation without the advice of your doctor or pharmacist” be used for Loperamide and Diphenoxylate.

additional requirements are also met.” · In relation to use in pregnancy, the TGA notes that while

Atropine and Hyoscine are both classified as pregnancy Category A, Hyoscyamine is in Category B2. These three substances currently do not have any advisory statements. However, the current Australian Regulatory Guideline for OTC Medicine (ARGOM 2003) recommends that where the product contains active ingredient(s) that are included in any pregnancy category other than category A, then the label should include a statement advising consumers who are pregnant or who may become pregnant to check with their doctor or pharmacist before taking or using the medicine.

· Therefore, taking into account the Guild’s suggestions and the information detailed above, the TGA proposes that a new statement “Do not use during pregnancy or breastfeeding without the advice of your doctor or pharmacist” be introduced and be required for Hyoscyamine.

Outcome 1. Remove grouping for anticholinergics. 2. Create separate entries for Atropa belladonna, Atropine compounds (excluding Atropine methonitrate), Datura spp, Hyoscine compounds,

Hyoscyamine and Hyoscyamus niger. 3. All except for Hyoscyamine will require the statement “If the condition persists after two days of treatment, seek medical advice as soon as

possible. 4. Hyoscyamine will require both statements “If the condition persists after two days of treatment, seek medical advice as soon as possible” and

“Do not use during pregnancy or breastfeeding unless advised by your doctor or pharmacist” 5. Amend the requirements for Loperamide and Diphenoxylate to require both statements “If the condition persists after two days of

treatment, seek medical advice as soon as possible” and “Do not use during pregnancy or breastfeeding unless advised by your doctor or pharmacist” instead of RASML statement 17.

Histor

ical

doc

umen

t



Page 17 of 51

Aspartame



· ASMI questions the need for more stringent warning given that Aspartame is included in the first schedule of Therapeutic Goods Order (TGO) 69 which requires Aspartame (and Phenylalanine) to be declared on label. Additionally, the Required Advisory Statements for Medicine Labels (RASML 2008) currently states that unless otherwise specified in column 2 of the table in section 1, the requirements apply only if the substance is included in the medicine as an active ingredient. As Aspartame is only used as an excipient in Over-the-counter and Listed medicines, and it is already declared on labels, ASMI questions the entry in the consultation which has created a concern of whether the scope of RASML is changing.

· ASMI suggests deleting the entry.

· Given the known safety concerns related to use of particular substances by phenylketonurics, the TGA is of the opinion that individuals with this condition would want/need to be advised of all possible sources.

· Electronic Listing Facility (ELF) has required that products containing Aspartame (as active or excipient) include the advisory statement 193 since 2001. Therefore, the TGA is of the view that there has been no change in the requirements in relation to the use of this ingredient in Listed medicines. In addition, the RASML document is often used as a reference document for advisory statements requirement, therefore the addition of Aspartame would allow for easy reference.

· However, the TGA does agree that the condition for the aspartame entry should be amended for greater clarity.

Outcome 1. Amend condition to “when for oral ingestion and included in medicines as an active or excipient ingredient”

Aspirin



· ASMI notes the inappropriateness of including advisory statement 128 on products indicated for the prevention of cardiovascular disease or for the inhibition of platelet aggregation as these products are intended for longer term use for this indication. ASMI points out that it will create confusion for consumers to read that these products should not be taken “for more than a few days at a time”.

· ASMI suggests that the requirement for advisory statement 128 for products

· The TGA agrees with ASMI that the advisory statement 128 would be inappropriate for products which are indicated solely for prevention of cardiovascular disease or for the inhibition of platelet aggregation.

Histor

ical

doc

umen

t



Page 18 of 51


indicated exclusively for cardiovascular use is deleted.

Outcome 1. Remove the requirement of statement 128 from Aspirin Entries 2, 3 and 4

Chlorhexidine



· ASMI raises the concern that the recommendations by the MEC and the proposal to require advisory statements are not in accordance with NDPSC recommendations by not including a 1% cut-off for Chlorhexidine products. ASMI also points out that the NDPSC exempted solid dosage formulations of Chlorhexidine from the SUSMP on the basis that these formulations would not present an eye irritancy hazard to the user, and that the NDPSC did not recommend the need for warning statements for those products in S5, S6 and S7. ASMI considers that the proposal to require advisory statements 79, 85 and 114 should not apply to products containing <1% Chlorhexidine and requests the TGA to reconsider previous recommendations.

· Bayer requests that further consideration of a cut-off level, i.e. 1% concentration above which the advisory statements should apply, and that the appropriateness of each statement should also be considered against dosage form, strength and use.

· The TGA considers that consumers should be adequately advised to discontinue use if skin irritation is severe, and to rinse the product out of the eyes if necessary. The MEC did not recommend the inclusion of any cut-off percentage for the requirements of applying advisory statements, the TGA considers those susceptible to Chlorhexidine may experience skin/eye irritation regardless of its concentration. Any topical products containing Chlorhexidine, regardless of strength and use, may have the potential to cause irritation to the skin and/or eyes (e.g. accidental contact with the eyes after topical application of Chlorhexidine cream on the hands/fingers).

Outcome 1. Retain current condition for Chlorhexidine


· Colgate Palmolive asserts that there are many mouth rinses/gels that contain Chlorhexidine that are supplied in the Australian marketplace which are not regulated as medicines, and these products would not be subject to any warnings imposed by the Required Advisory Statements for Medicine Labels (RASML). Therefore Colgate Palmolive advocates that risk assessment of Chlorhexidine when used in topical products should be the appropriate criteria for determining the use of the warnings statements on labelling.

· The record of decisions from the meetings of the NDPSC has been published since 1999 and is available on the TGA website. The decision made by NDPSC to include Chlorhexidine in Schedule 7 of the SUSMP with a cut-off to Schedule 6 for preparations containing 7% or less, Schedule 5 for 3% or less and an exemption to unscheduled for 1% or less or when in solid

Histor

ical

doc

umen

t



Page 19 of 51


· Colgate Palmolive suggests that the SUSMP is the appropriate risk assessment process for consideration of a warning statement for Chlorhexidine, as the SUSMP applies to all Chlorhexidine containing products with participation by the Industry for consideration of any toxicologically supported concentration thresholds

· ACCORD asserts that the TGA’s proposal to apply advisory statements to Chlorhexidine is inconsistent with international regulatory approaches, which are supported by expert reviews of the safety and toxicology of Chlorhexidine. For Chlorhexidine which is used in products that can be registered as a medicine, but also sold as a consumer product (e.g. mouthwash) there has been no scientific justification for stating that all Chlorhexidine containing medicines will require mandatory statements, when these statements are not required for similar consumer products. In particular, cut-off percentages for the proposed labelling requirements have not been provided.

· ACCORD also proposes that the SUSMP is the appropriate forum to evaluate the risk assessment of Chlorhexidine when used in topical products to determine the appropriate criteria and cutoffs for warnings statements on labelling, and recommends TGA refer this substance to the scheduling process.

· ASMI contends that the NDPSC did not recommend the need for warning statements, even for those Chlorhexidine products included in Schedules 5, 6 and 7. In addition, ASMI express concerns that the MEC’s recommendations and therefore the advisory statements are not in accordance with the NDPSC recommendations by not including a 1% cut-off for Chlorhexidine preparations. Therefore ASMI does not consider that the advisory statements for products containing < 1% Chlorhexidine are required.

· ASMI proposes changing the condition to “When included in topical products for human use containing 1% or more of Chlorhexidine.”

· ASMI suggest a separate line entry for requiring the new advisory statement 212, as it is only intended to apply to products used on mucosal surfaces. It is proposed that the new entry for Chlorhexidine have the condition set out as “When containing Chlorhexidine and included in preparations for topical use on mucosal surfaces.”

· ASMI further suggests that when the advisory statement 212 is required, then it may

preparations; was made on the basis of the potential for inhalational toxicity and severe eye irritancy. The NDPSC also “noted that Chlorhexidine was not listed in the Required Advisory Statements for Medicine Labels (RASML). The NDPSC considered referring the issue of labelling of Chlorhexidine for human use to the OTC Section”. Consequently, advice was sought from the Medicines Evaluation Committee on appropriate advisory statements to be applied. RASML statements 79 “avoid contact with eyes” and 85 “if in eyes, rinse well with water” were proposed by MEC to be included in the RASML document.

· At the same time, the MEC was advised of the Adverse Drug Reactions Advisory Committee (ADRAC) review of reported adverse reactions to products containing Chlorhexidine. It was noted that the adverse reaction reports did not distinguish a particular concentration of Chlorhexidine that resulted in adverse reactions experienced. Consequently, the MEC did not recommend the inclusion of any cut-off percentage for the requirement of applying advisory statements.

· The TGA considers those susceptible to Chlorhexidine may experience skin/eye irritation regardless of its concentration. Any topical products containing Chlorhexidine, regardless of strength and use, may have the potential to cause irritation to the skin and/or eyes (e.g. accidental contact with the eyes after topical application of Chlorhexidine cream on the hands/fingers). Due to potential safety concerns, the TGA considered that the advisory statements should apply to all topical products containing Chlorhexidine.

Histor

ical

doc

umen

t



Page 20 of 51


not be necessary to include advisory statement 114, as it is unreasonable to expect a consumer to be able to differentiate between an ‘irritancy’ and an ‘allergic reaction’. Both advisory statements are very similar and both require treatment to stop in case of a severe reaction. Therefore delete requirement for advisory statement 114.

· The Pharmacy guild notes that advisory statemet114 should not be needed with advisory statement 212 and proposes that only advisory statement 212 be required for Chlorhexidine.

· However, TGA agrees with the comments from ASMI and the Pharmacy Guild that having both advisory statements 114 and 212 would be incongruous and lead to confusion. Therefore the TGA propose inclusion of a new entry for products containing Chlorhexidine.

Outcome 2. Amend condition to “when included in preparation for human use, including preparations for topical use on mucosal surfaces” to require advisory statements 79, 85 and 212.

3. Add new entry and condition “ when included in topical products for human use and NOT included in preparations for topical use on mucosal surfaces” to require advisory statements 79, 85 and 114

Choline Salicylate



· Dr Ken Harvey submitted an article which raising his concern that both the old “stated dose” and the proposed “recommended dose” label warnings are ambiguous and unhelpful. He proposes that both the dose and duration of use for these products be better defined.

· The proposal that both the dose and duration of use for these products be better defined, relates specifically to the ambiguity of the recommended dose and duration of use of this product which falls outside the scope of the Required Advisory Statement for Medicines Label. The TGA concurs with the comments, but propose that this matter can be separately addressed during the evaluation and registration process.

Outcome No outcome action

Histor

ical

doc

umen

t



Page 21 of 51

Decongestant, oral (Phenylephrine, Pseudoephedrine)



· ASMI points out that sponsors currently apply “May cause sleeplessness” to labels of Phenylephrine products and that Phenylephrine has an approximate 2.5 hour half life, compared with a 6 hour half-life for Pseudoephedrine. Therefore ASMI contends that it is unnecessary to specify ‘up to several hours before going to bed’ as they are not aware of any specific data that warrants this more restrictive statement.

· ASMI suggests removing the requirement for the advisory statement 209 for Phenylephrine or amend it to “This product may cause sleeplessness”.

· The TGA agrees with ASMI that the advisory statement 209 should only apply to Pseudoephedrine. Therefore a new statement is to be introduced to apply to products containing Phenylephrine.

Outcome 1. Remove requirement for statement 209 for Phenylephrine. 2. Introduce a new advisory statement “This product may cause sleeplessness” for products containing Phenylephrine.

Excipients (Butylester of pvm/ma copolymer, DEA-Oleth-3 phosphate, Diethylhexyl-2,6-napthalate, Erythrulose, Ethyl butylacetyl-aminopropionate, Stearamidopropyl PG-dimonium chloride phosphate, Stearyl dimethicone, Sucrose polycottonseedate)



· ACCORD would support the consideration of the substances proposed by TGA as eye irritants to be assessed by the scheduling process, with the ACCS & ACMS to make recommendations on appropriate scheduling cutoffs, rather than RASML implementing warnings for the list of substances proposed, without consideration of threshold limits below which no eye irritancy occurs. For those substances that already have applicable schedule entries (e.g. quaternary ammonium compounds such as Stearamidopropyl PGdimonium chloride phosphate), ACCORD suggests that RASML adopts the SUSMP entry.

· The advisory statements 79 and 215 are currently incorporated in ELF as required statements for these ingredients, and this has been the case since these ingredients were approved for use in listed medicines.

· However, the concerns expressed in the consultation warrants further review by the TGA. Further comment on the toxicological assessment process for new topical excipients for listed medicines will be sought.

Outcome 1. Requirement for advisory statements for the list of substances proposed not to be implemented for this update.

Histor

ical

doc

umen

t



Page 22 of 51

Fluorides



· Colgate-Palmolive queries the justification for the new advisory statements for Fluoride, which go beyond the SUSMP Fluoride entry requirements.

· ACCORD does not support the addition of new advisory statements for Fluoride containing medicines which have not been justified from a risk perspective. ACCORD believes that the SUSMP is the appropriate control mechanism for safety related warnings. Furthermore ACCORD asserts that the addition of these advisory statements via RASML would cause confusion for consumers due to the presence of equivalent concentration Fluoride products that are cosmetics, which would be required to comply with the SUSMP.

· A sponsor has noted that based on the new draft ARGOM, the warning statements were intended for Fluoride supplementation products such as tablets and drops. The sponsor maintains that new additional warning statements are not appropriate for dental hygiene products including mouthwashes as these types of products are applied topically and are not intended to prove supplementary Fluoride as the Fluoride is not absorbed systemically.

· The sponsor proposes that a specific entry for Fluoride supplements (or Fluoride products intended to be ingested) should to be created and that the advisory statements 13, 40 and 210 be applied to that specific group only. The current RASML statements 122, 150 should remain as the only warning statements for Fluoride dental hygiene products.

· ASMI notes that the current proposed condition implies that the advisory statements would be required for all Fluoride containing non prescription medicines which does not reflect the requirements as set out in ARGOM which only extends to Fluoride supplements (such as tablets and drops).

· ASMI further notes that the proposed condition would apply to ALL Fluoride products excluded from the schedules, including mouthwashes and toothpastes, whilst not having an entry for Fluoride when included in the schedules so that the warnings would no longer apply to Fluoride supplements.

· The TGA considers the comments from the various stakeholders and agrees that the proposed condition text was insufficient to differentiate Fluoride products which would require the warning statements. Therefore the TGA accepts the proposal from the sponsor and ASMI.

Histor

ical

doc

umen

t



Page 23 of 51


· Therefore ASMI asserts that the advisory statements 13, 40, 210, should not be required for Fluoride products excluded from scheduling.

· ASMI proposes that two new Fluoride entries with the condition “When included in a schedule to the SUSMP” and “When in Fluoride Supplements” be introduced.

Outcome 1. Include a new entry for Fluoride with the condition “when included in a Schedule to the SUSMP except Fluoride supplements ” and requiring statement 122 and 150

2. Include a new entry for Fluoride with the condition “when in oral preparations as Fluoride supplements” which will require statement 13, 40, 210

Folic acid



· Bayer does not support the proposal that the advisory statement 183 be required for all non-prescription folic acid containing products as there is no need for OTC or registered complementary medicines which require evaluation to carry the same warning statements.

· Bayer recommends exemption be given to products that have undergone evaluation by the TGA

· The TGA considers it an appropriate advisory statement for expectant mothers taking Folic acid supplement medicines specifically indicated to reduce the risk of spina bifida/neural tube defects, particularly if they have previously had a child with these conditions. The conditions sets out that the advisory statement is only required when indicated for reducing the risk of having a child spina bifida/neural tube defects, therefore it does not capture all non-prescription Folic acid containing products.

Outcome 1. Retain condition

Histor

ical

doc

umen

t



Page 24 of 51

Hydrolysed milk protein - alpha casozepine enriched



· CHC notes that the transition period for this substance should be amended to "immediate". This ingredient was recently listed with a condition for the required advisory statements to be placed on the label. Sponsors should already have this statement on the label of their products.

· The TGA agrees with CHC

Outcome 1. Transition period for this substance amended to “immediate”

Hypericum Perforatum



· The Pharmacy Guild notes that consumers are as or more likely to receive advice from a pharmacist as a doctor (even for referral), therefore proposes replacing advisory statement 68 “Consult your doctor” with a revised advisory statement 64

· The TGA notes the merit of this recommendation and propose consideration be given to presenting them for the next future consultation for updating RASML.


Imidazoles (Butoconazole, Clotrimazole, Econazole, Miconazole, Oxiconazole, Tioconazole)



· Apotex notes that the advisory statement 75 refers patient to see a doctor or dentist. Apotex proposes removal of advisory statement 75 as OTC Clotrimazole not likely to be used in any dental procedures and so would not be initiated by a dentist.

· Bayer does not support the inclusion of RASML statement 13. Bayer argues that vaginal candidiasis is a common infection during pregnancy leaving topical anti-fungal imidazoles the most common form of treatment during pregnancy. Therefore for Clotrimazole to be contraindicated in pregnant women would leave no other

· It should be noted that advisory statement 75 applies to imidazole fungal preparation, nystatin and triamcinolone. Triamcinolone can be prescribed by dentist to treat mouth ulcers. The advisory statement places the word “dentist” in brackets to indicate that sponsors have the flexibility of removing reference to dentist if the product is not being used in dental procedures. Therefore the

Histor

ical

doc

umen

t



Page 25 of 51


efficacious medicines available to treat women during pregnancy. · Bayer proposes that Schedule 3 imidazole vaginal products should not be required to

have advisory statement 13 and to reinstate the requirement for advisory statement 16 instead.

· ASMI shared similar concerns and does not support the new RASML statement 13 for the ingredients belonging to the imidazole class.

· ASMI recommends deleting the requirement for advisory statement 13 for Clotrimazole, Econazole and Miconazole in vaginal preparations when included in Schedule 3 of the SUSMP; and to only apply advisory statement 16 to these ingredients.

· The Pharmacy Guild notes the inconsistency in requiring both advisory statement 13 and advisory statement 16.

TGA does not agree that there is a need to remove advisory statement 75

· The TGA concurs with the comments from the various stakeholders, and agrees with the proposal to remove the requirement for advisory statement 13 to apply to Clotrimazole, Econazole and Miconazole; and to only apply advisory statement 16 to these ingredients.

Outcome 1. Delete requirement for statement 13 for Clotrimazole, Econazole and Miconazole in vaginal preparation when included in Schedule 3 of the SUSMP.

2. Statement 13 continues to be applied to Fluconazole which is classified as Category D. 3. Statement 13 continues to be applied to Tioconazole, Oxiconazole which are currently unclassified but current evidence suggest that it

would fall under Category C and D 4. Delete class entry for imidazoles.

Non steroidal anti-inflammatory drugs (NSAIDs) (Benzydamine, Diclofenac, Flurbiprofen, Ibuprofen, Indomethacin, Ketoprofen, Naproxen, Mefenamic acid)



· Roche comments on the inconsistency between the information in the SUSMP with respect to the NSAIDs which has the result of implying that some of the NSAIDs need to comply with RASML even when scheduled in Schedule 4. E.g. Aspirin, Ibuprofen both require compliance with RASML in SUSMP Schedule 2 entry. Diclofenac,

· The TGA notes that the comments from Roche. As this relates to changes to the SUSMP, no further action is required. In addition, it should be noted that recent changes to the Therapeutic Goods Act has resulted in

Histor

ical

doc

umen

t



Page 26 of 51


Indomethacin and Naproxen does not require compliance with RASML in SUSMP Schedule 2 entry.

· Roche proposes that for clarity and consistency, the Schedule 2 SUSMP entry for all NSAIDs that are also included in Schedule 4 should state “Compliant with the requirements of the RASML” which would preclude the medicines when packaged and presented as prescription products from the requirements of RASML

· The Pharmaceutical Society of Australia (PSA) observes that due to interaction of NSAIDs and thiazide diuretics, consideration should be given to including a statement alerting consumers to see a doctor before taking an NSAID if they are being treated for high blood pressure or taking diuretics.

· PSA propose that a new statement with additional cautionary wording be included.

Advisory statement 192

· A sponsor observes that the advisory statement 192 is not specific to children, nor does it specify use as an analgesic therefore the sponsor believes it is unnecessarily broad. The sponsor also argues that it should not be a requirement to include this warning on products containing ibuprofen that are indicated for cold and flu or sinus, since these are usually used for short term relief of symptoms related to self limiting colds or flu rather than pain.

· The sponsor also alludes to the requirement for a similar warning specifically on children’s products by Medsafe. The Medsafe warning relates to children suffering dehydration through diarrhoea and/or vomiting. Since children and babies are most vulnerable to rapid dehydration due to their large surface area:volume ratio, the sponsor believes that the Medsafe warning is more specific and adoption of the Medsafe warning would also allow alignment with Australian/New Zealand labelling

· Therefore the sponsor suggests, in alignment with Medsafe requirements, the advisory statement 192 should apply only to ibuprofen products for use in children and to analgesic products containing ibuprofen and to exclude cold & flu preparations containing ibuprofen.

· In addition to not supporting the advisory statement to apply both adults and

RASML being only applicable to non prescription medicines.

· The TGA is aware of the interaction of NSAIDs with thiazide diurectics. However, as NSAIDS can potentially interact with many medicines, it may be inappropriate to only single out thiazide diuretics. TGA considers that the proposal to amend advisory statement 149 “Unless a doctor has told you to, do not use [this product/insert name of product] with medicines containing [insert name of substance], aspirin, or other anti-inflammatory medicines or with medicines that you are taking regularly” can address the issue of potential interactions between NSAIDS and all other medicines.


· The TGA agrees that the advisory statement 192 should only be applied to NSAIDS which have paediatric doses and agrees to amend the wording of the statement to align with the Medsafe requirements

· However, the TGA does not agree that Flurbiprofen should be exempt from the requirement for advisory statement 192. Although Flurbiprofen is available as a lozenge form for topical use to treat sore throats, it can be swallowed orally and therefore have the same adverse effects as other oral forms of NSAIDs. The argument put forward by ASMI regarding the unlikeliness that the products will be used if already suffering from vomiting or diarrhoea or that it is difficult for consumer to determine if they are dehydrate also extends to other oral forms of NSAIDs, therefore Flurbiprofen cannot be singled out as being unique to be exempt from the

Histor

ical

doc

umen

t



Page 27 of 51


children, ASMI further observes that wording of the warning does not provide guidance to consumers that vomiting and diarrhoea are examples of when they might be dehydrated. ASMI queries a consumer’s ability to determine if they are dehydrated.

· ASMI notes that in New Zealand a similar statement is required on liquid preparations for paediatric use. ASMI believes that that the Medsafe wording for liquid paediatric products “Use of the medicine without a doctor’s advice is contraindicated in children suffering dehydration through diarrhoea and/or vomiting” is more helpful in explaining to consumers that vomiting and diarrhoea may lead to dehydration.

· Therefore ASMI proposes that the advisory Statement 192 should be applied only to paediatric dose products. The wording should be amended consistent with the more consumer friendly Medsafe wording - “Ask your doctor or pharmacist before use of the medicine in children suffering dehydration through diarrhoea and/or vomiting”

· In addition, ASMI does not consider that the advisory statement 192 is required for lozenges containing Flurbiprofen, especially as the sugar in the product may in itself cause diarrhoea. ASMI contends that it is unlikely the products will be used if already suffering with vomiting or diarrhoea; and it is difficult for a consumer to determine if they are dehydrated. Further, as the label will need to advise not to take with other medicines regularly being taken, it would be unnecessary to include RASML statement 192.

· ASMI proposes that there should be no requirement for the advisory statement 192 be applied to Flurbiprofen


· ASMI questions if consumers would understand the intended meaning of heart failure. ASMI suggests that consumers would potentially perceive it to mean “I should not take this medicine when I am having a heart attack”, rather than the intended “I should not take this medicine if I have any type of heart condition”.

· ASMI proposes that the advisory statement 201 be reworded to more consumer

requirement.


· TGA considers the proposal put forward by ASMI to amend the words “heart failure” to “heart problems” or “heart conditions” would capture a much broader population and may exclude those patients who could otherwise take OTC NSAIDs. In addition, the advisory statement 201 is intended for those who have been medically diagnosed with heart failure and would therefore recognise the term. Therefore TGA is of the view that the original advisory statement is more appropriate. However, RASML does allow that “wording of the statements may be varied provided that the intent is not changed.”, therefore products which have advisory statements that uses the term “heart problems” would be considered to be compliant with RASML and the labels would not be required to be amended

Histor

ical

doc

umen

t



Page 28 of 51


friendly terms such as “Do not use if you have heart problems”, or “Do not use if you have a heart condition.”

Outcome 1. Introduce new entry with the condition “when the preparation is indicated for use in children”. 2. Amend statement 192 to “Ask your doctor or pharmacist before use of the medicine in children suffering dehydration through diarrhoea

and/or vomiting”

Potassium chloride



· CHC recommends that the proposed condition “when included in non-prescription medicines for oral ingestion” should be amended to apply only to products for oral rehydration therapy.

· The TGA agrees that amendment should be made to the condition to only apply to products for oral rehydration therapy

Outcome 1. Amend condition to “ When included in Listed medicines for oral rehydration therapy”

Proton pump Inhibitors (Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole)



· PSA points out that the interaction of proton pump inhibitors (PPI) with Clopidogrel should warrant consideration of inclusion of a warning statement to seek health professional advice if using blood thinning medicines.

· TGA considers that it would be misleading if consumers are only warned about this particular interaction and not to other interactions and may assume that they do not need to check if they are not taking Clopidogrel. Therefore the TGA is of the opinion that the advisory statement 223 is sufficient in addressing the issue of all possible interactions between PPIs and Clopidogrel.


Histor

ical

doc

umen

t



Page 29 of 51

Psyllium



· CHC notes that the advisory statement for Psyllium would include all Listed medicines for oral ingestion, and should only apply to these products when they provide a dose for children

· The TGA agrees that the condition for Psyllium be amended.

Outcome 1. Amend condition to “When included in non-prescription medicine for oral ingestion and the product contains dosage instructions for children.”

Pyridoxal, Pyridoxamine, and Pyridoxine



· A stakeholder expresses concerns that the statements would deter consumers from using these products. He argues that there is research to support the use of vitamin B6 in a range of conditions. He states that the label warning should only apply to products that contain more than 100 mg of vitamin B6.

· The quantity restriction is an entry in the SUSMP. The TGA notes that the indications that the stakeholder referred to were not appropriate for Listed medicines.

Outcome 1. Retain condition.

Vasoconstrictor eye drops (Naphazoline, Phenylephrine, Tetrahydrozoline)



· As for comments for Phenylephrine as a nasal decongestant ASMI queries the need for the advisory statement 209.

· ASMI proposes the removal of the requirement for RASML statement 209 to apply to Phenylephrine

· The TGA agrees with ASMI that Phenylephrine in topical preparations would not require advisory statement 209.

Outcome 1. Remove requirement for statement 209 for eye drops containing Phenylephrine

Histor

ical

doc

umen

t



Page 30 of 51

Clarify ‘words to the effect’



· ASMI seeks to clarify that “words to the effect’ were acceptable for all the proposed advisory statements.

· In line with the requirements in the current RASML Edition 1 (including Update 4) that “the wording of the statements may be varied provided that the intent is not changed,” therefore ‘words to the effect’ is acceptable for all advisory statements provided that the intent is not changed.


Package Labelling



· Bayer requests that due consideration be given to allow the required information from the five RASML statements be given the option to be either placed on the product label or the patient information leaflets (PIL), noting that the definition or interpretation of ‘label’ is broader in the Act compared to that in the RASML document or TGO69. Bayer considers that the option to allow RASML statements to be placed in the PIL for S3 products can be legislatively supported.

· A sponsor notes that whilst many patients have access to pharmacists, it is well known that comprehensive information on these products, such as Consumer Medicine Information sheets, are not routinely given to patients with each purchase or use. Therefore, for these products, the sponsor supports the implementation of the advisory statement 180 for the primary packaging. However the sponsor believes that the advisory statement 180 should not be required for primary package labelling if products already contain this same warning in an enclosed Package Insert. The sponsor also argues that the current enclosed package inserts already include the warning in bolded text in the first section, viz. "Always consult your doctor or pharmacist if pain does not improve within 48 hours or if pain worsens after treatment.

· The TGA did not agree with the proposal to allow RASML statements to be given the option to be either placed on the product label or the patient information leaflet for the following reasons: - Inclusion of advisory statements on the outer label

enables consumers, with the direct involvement of a pharmacist, to make an informed decision in self-selecting an appropriate S3 medicine on their own, taking into account their pre-existing condition and the advisory statements on the labels, and to use the medicine safely and effectively.

- Inclusion of advisory statements on the outer labels enables the consumer to read the necessary information before they purchase the product. In the case of the PIL, the consumer will not have access to the information until the product has been

Histor

ical

doc

umen

t



Page 31 of 51


· The sponsor proposes that the imposition of the warning should be restricted to those companies who do not include a registered package insert for their anticholinergic medicines. Moreover for those Companies who have an enclosed registered Package Insert with this warning clearly included, be given the choice about not including the additional warning on the primary packaging.

purchased. - Not all S3 products have PIL inserted in the pack. In

practice, this would cause confusion if one brand of a product with/without a PIL contains all the RASML advisory statements on the label but not on the label of a different brand of product containing the same active.

- Inclusion of advisory statements in PIL instead of labels may dilute the intent of the advisory statements, for example, in the case of sedation/alcohol advisory statements.

- The labels will not comply with the SUSMP, which clearly specifies that advisory statements must be included on the label.

· To cover short-term contingencies the TGA does allow sponsors, where necessary, to over-stick labels (under GMP conditions) with newly required advisory statements.

Outcome 1. The advisory statements must appear on the container label and any primary pack label

Histor

ical

doc

umen

t



Page 32 of 51

Section 2: The wording of the advisory statement(s) · Revised advisory statement 76 · Revised advisory statements 140 and 149 · Advisory statements 178 & 179 · Advisory statement 189 · Advisory statement 191 · Advisory statement 192 · Advisory statements 194 & 195 · Advisory statement 198 · Advisory statements 200 & 201 · Advisory statement 202 · Advisory statement 203 · Advisory statement 204 · Advisory statement 206 · Advisory statement 207 · Advisory statement 208 · Advisory statement 209

· Advisory statement 211 · Advisory statement 214 · Advisory statement 215 · Advisory statement 216 · Advisory statement 217 · Advisory statement 218 · Advisory statement 219 · Advisory statement 222 · Advisory statement 224 · Advisory statement 225 · Advisory statement 229 · Advisory statement 230 · Revision of advisory statements · Consolidating or archiving of advisory statements · Superseded advisory statements

Histor

ical

doc

umen

t



Page 31 of 51

Revised advisory statement 76 “If congestion persist for more than a few days, seek medical or pharmacist advice”



· ASMI states that they are aware that, as part of the registration process, products are required to include a precaution on using for more than a few days and rebound congestion. However, ASMI contends that the change in wording of the current advisory statement does not add anything useful.

· TGA agrees with the proposal that the current RASML statement “If congestion persists, consult your doctor or pharmacist” be maintained.

Outcome 1. Retain the current advisory statement without amendment.

Revised advisory statements 140 “Unless a doctor has told you to, do not use [this product/insert name of product] with other medicines containing other anti-inflammatory medicines or other medicines that you are taking regularly” and 149 “Unless a doctor has told you to, do not use [this product/insert name of product], aspirin or other anti-inflammatory medicines or other medicines that you are taking regularly”



· The Pharmacy Guild proposes that advisory statement 140 and advisory statement 149 be consolidated and to also identify OTC anti-inflammatory. In addition, it should be noted that consumers are more likely to receive advice from pharmacist as from a doctor.

· The Pharmacy Guild proposes two separate statements: 1. Adapted according to the contents: ‘Unless advised by your doctor or

pharmacist, do not use [this product/insert name of product] with other medicines containing aspirin, ibuprofen, naproxen, diclofenac or mefenamic acid [delete as appropriate]

2. ‘Consult your pharmacist or doctor if you take other medicines regularly’. · The Pharmaceutical Society of Australia (PSA) comments that the proposed new

wording for Statement 140 and 149 are unclear. It was noted that there were too many occurrences of “other” and “medicines”

· Note: The TGA notes that the revised advisory statement 140 in the consultation document should have read “Unless a doctor has told you to, do not use [this product/insert name of product] with other medicines containing aspirin or other anti- inflammatory medicines or other medicines that you are taking regularly.

· The TGA considers the consolidation of advisory statement 140 and advisory statement 149 as inappropriate due to advisory statement 140 being only applicable to Aspirin only, whilst advisory statement 149 applies to the rest of the NSAIDS. However, TGA does agree that each statement should be reworded to reduce the use of “other” and “medicines” as well as inclusion of reference to a pharmacist. It should be noted that the RASML does allow “the wording of the statements may be

Histor

ical

doc

umen

t



Page 32 of 51


varied provided that the intent is not changed”

Outcome 1. Amend RASML 140 to “ Unless advised by your doctor or pharmacist, do not use [this product/inset name of product] with other products containing aspirin or anti-inflammatory medicines or with medicines that you are taking regularly”

2. Amend RASML 149 to “Unless advised by your doctor or pharmacist, do not use [this product/insert name of product] with products containing [insert name of substance], aspirin, or other anti-inflammatory medicines or with medicines that you are taking regularly”

Advisory statements 178 “ WARNING – Stop taking this medication if you experience tingling burning or numbness and see your healthcare practitioner as soon as possible” and 179 “ WARNING – Stop taking this medication if you experience tingling, burning, or numbness and see your healthcare practitioner as soon as possible. Contains vitamin B6”



· The CHC proposes a warning statement similar to “WARNING – Exceeding the recommended daily dose of vitamin B6 may be harmful. Consult your healthcare practitioner for advice".

· The Pharmacy Guild proposes the following alternative advisory statements: o For single ingredient products -“WARNING – This medication may be dangerous when used in

large amounts or for a long period. Stop taking this medication if you experience tingling, burning or numbness and see your healthcare practitioner as soon as possible”

o For multi-ingredient products -“WARNING – This product contains vitamin B6 which may be dangerous when used in large amounts or for a long period. Stop taking this medication if you experience tingling, burning or numbness and see your healthcare practitioner as soon as possible"

· The TGA considers that the majority of consumers were unlikely to consult a healthcare practitioner before using a Listed medicine and preferred the wording proposed by the Pharmacy Guild. However, the Pharmacy Guild proposed statements would take up more space on a label than the previous statements particularly if the product is a multi-ingredient one.

Outcome 2. Retain the advisory statements without amendment.

Histor

ical

doc

umen

t



Page 33 of 51

Advisory statement 189 “This product may cause photosensitisation”



· The Pharmacy Guild recommends that the advisory statement 189 ”This product may cause photosensitisation” be amended to "This product may make the skin extra sensitive to sunlight - use appropriate precautions if exposed" or words to that effect.

· In a review of the requirement for an advisory statement to apply to Psoralea corylifolia, the TGA considers that it need not be implemented.

Outcome 1. Requirement for the advisory statement 189 for Psoralea corylifolia not to be implemented for this update

Advisory statement 191“There is no benefit from taking more than 3 g/ day of phytosterols from all sources”



· CHC recommends that the advisory statement 191 be amended as the wording ‘no benefit’ is inaccurate. The CHC also considers clarification should be given between phytosterols and phytosterols ester dose limits. Wording similar to – ‘There is minimal benefit from taking more than 3g/day of phytosterols and 5g/day of phytosterols esters, from all sources’ would be more accurate.

· The advisory statement 191 cannot be altered due to it being a requirement as set out in Therapeutic Goods (Listing) Notice 2008 (No. 6).

Outcome 1. Retain the advisory statement 191 without amendment


· A sponsor observes that he Listing Notice 2010 (No.1) does not include ‘For lowering cholesterol uptake’, therefore it should be removed from the advisory statement 191.

· The TGA agrees, there was an error in the advisory statement 191 contained in the consultation document.

Outcome 1. Correction of advisory statement 191 to as per Listing Notice 2010 (No.1)

Histor

ical

doc

umen

t



Page 34 of 51

Advisory statement 192 “Ask your doctor or pharmacist before use if you are dehydrated, or have diarrhoea or vomiting”



· A sponsor alludes to the requirement for a similar warning specifically on children’s products by Medsafe. The Medsafe warning relates to children suffering dehydration through diarrhoea and/or vomiting. Since children and babies are most vulnerable to rapid dehydration due to their large surface area:volume ratio, the sponsor believes that the Medsafe warning is more specific and adoption of the Medsafe warning would also allow alignment with Australian/New Zealand labelling.

· The TGA agrees that the advisory statement 192 should only be applied to NSAIDS which have paediatric doses and agrees to amend the wording of the statement to align with the Medsafe requirements (See Section 1: Application of advisory statement to medicines: Non steroidal anti-inflammatory drugs (NSAIDs) (Benzydamine, Diclofenac, Flurbiprofen, Ibuprofen, Indomethacin, Ketoprofen, Naproxen, Mefenamic acid))

Outcome 1. Amend statement 192 to “Ask your doctor or pharmacist before use of the medicine in children suffering dehydration through diarrhoea and/or vomiting”

Advisory statements 194 “This product may make your skin more sensitive to sunlight” and 195 “Sun exposure should be limited by using a sunscreen and by wearing protective clothing”



· The Pharmacy Guild contends that the advisory Statement 194 and advisory statement 195 are duplications of advisory statement 70 “Avoid excessive exposure to sunlight and other sources of ultra violet light” and advisory statement 93 “Application to skin may increase sensitivity to sunlight”

· The Pharmacy Guild recommends consolidating advisory statements 70, 93 & 194 then using with advisory statement 195 as appropriate. ‘This product may make your skin more sensitive to sunlight or other sources of UV light’ is proposed as the consolidated advisory statement.

· The TGA does not agree that the advisory statements 70, 93 and 194 can be consolidated at this time. Advisory statement 70 applies to orally ingested medicines which can cause photosensitivity whilst advisory statement 93 and 194 applies to products for topical use. However for consistency, the TGA considers that the advisory statement 194 should be amended to reflect the wording of advisory statement 70 with the view that the advisory statement 194 and 195 replace advisory statement 93 in the future update of the RASML.

Outcome 1. Amend statement 194 to “This product may make your skin more sensitive to sunlight or other sources of UV light”.

Histor

ical

doc

umen

t



Page 35 of 51

Advisory statement 198 “If diarrhoea persists seek medical advice”



· The Pharmacy Guild asserts that this may be confusing and is inconsistent with other terminology referring to doctor/pharmacist. Suggest replacement with doctor and/or pharmacist as appropriate

· The advisory statement 198 is set out in accordance with the Listing Notice 2009 (No. 3), therefore it cannot be amended.

Outcome 1. Retain the advisory statement without amendment

Advisory statements 200 “Do not use if you have impaired kidney function” and 201 “Do not use if you have heart failure”



· The Pharmacy Guild maintains that blood pressure may also be affected by NSAIDs due to sodium & fluid retention from NSAID-induced reduction in glomerular filtration rate & renal blood flow. In addition, the Pharmacy Guild also notes that the advisory statements 200 and 201 duplicates intention of advisory statement 166 “If you have kidney disease or are taking heart or blood pressure medicine, consult your doctor or pharmacist before use.

· The Pharmacy Guild proposes using the advisory statement 166 instead of the advisory statements 200 and 201.

· The TGA does not agree that the advisory statements 200 and 201 can be substituted by advisory statement 166. The introduction of these statements is to advise those who have impaired kidney functions and heart failure to not use NSAIDS at all. Advisory statement 166 (which currently applies to Glucosamine and Potassium Chloride) advises the patient to consult a doctor or pharmacist prior to use and does not imply that it cannot be used at all. Therefore, it would not be appropriate to apply advisory statement 166 for NSAIDs

Outcome 1. Retain the advisory statements without amendment

Histor

ical

doc

umen

t



Page 36 of 51

Advisory statement 202 “Unless a doctor has told you to, do not use [this product/product name] with other medicines that you are taking regularly”



· The Pharmacy Guild observes that consumers are as or more likely to receive advice from a pharmacist as a doctor. It would be more appropriate to refer consumers to the pharmacist as well as the doctor to facilitate health professional intervention.

· The TGA agrees that the advisory statement 202 be amended to included reference to a pharmacist

Outcome 1. Amend advisory statement 202 to “Unless a doctor or a pharmacist has told you to, do not use [this product/product name] with other medicines that you are taking regularly”

Advisory statement 203 “Do not take hot food or drink soon after using this product because it may burn your mouth”



· CHF recommends that the advisory statement 203 should provide consumers with an indication of how long they should refrain from eating or drinking hot foods and beverages, as “soon after” is insufficiently specific. If it is not possible to provide this information on the label, consumers should be advised to consult their doctor or pharmacist.

· The TGA agrees with CHF. However there are no data to indicate a quantifiable time that a person will need to refrain from eating and drinking hot foods. Therefore, an alternative wording of the statement is provided.

Outcome 1. Amend advisory statement 203 to “Do not take hot food or drink if the mouth feels numb after taking this product as it may burn the mouth”

Advisory statement 204 “Do not give to children under 6 years of age, unless recommended by a doctor, pharmacist or dental professional”



· The Pharmacy Guild notes that the advisory statement duplicates the intent of advisory statement 131 “Unless a doctor has told you to, do not use [this product/insert name of product] in children 6 years of age or less” and advisory statement 150 “Do not use this [product/insert name of product] in children 6 years

· The TGA does not agree with the proposal to consolidate the statements. Although the advisory statement 204 appears to be similar to advisory statement 113, it advises consumers that the anaesthetic lozenge may be

Histor

ical

doc

umen

t



Page 37 of 51


of age or less”. · The Pharmacy Guild proposes that these advisory statements are consolidated and to

reference one only as well as using “dentist” instead of “dental professional”.

given on advice from a doctor, pharmacist or a dental professional. To amend statement 131 to include dental profession will result in a warning statement that would be inappropriate for ibuprofen, to which statement 131 applies. Advisory statement 150 advises that the product should not be given to children under 6 years of age under any circumstances, therefore it would be inappropriate to consolidate this statement with others.

· The TGA agrees with the Pharmacy Guild that the advisory statement refers to “dentist” instead of “dental profession”

Outcome 1. Amend advisory statement 204 to “Do not give to children under 6 years of age, unless recommended by a doctor, pharmacist or dentist”

Advisory statement 206 “This product is for temporary use”



· The Pharmacy Guild contends that ‘temporary use’ should be defined and that the advisory statement 206 duplicates the intent of advisory statement 128 “Unless a doctor has told you to, do not use [this product/insert name of product] for more than a few days at a time” and advisory statement 144 “Do not take this medicine for longer than a few days at a time unless advised to by a doctor”.

· The Pharmacy Guild proposes the consolidation of the advisory statements 128, 144 & 206 to “This product is intended for short-term use only of [not more than a few days / or X days]”. Then use with advisory statement 226 “Prolonged use may be harmful”.

· The TGA agrees with the Pharmacy Guild that statement 206 should be amended to be more appropriately defined. However, it would be inappropriate to consolidate the advisory statement 206 with advisory statements 128 and 144 as both these advisory statements are specifically applicable to medicines which differ from each other in safety profiles and has the intention of advising that the consumers can take the medicine for longer than a few days on advice from a doctor.

Outcome 1. Amend advisory statement 206 to “Do not take this medicines for more than a few days”

Histor

ical

doc

umen

t



Page 38 of 51

Advisory statement 207 “Do not use for prolonged periods except on the advice of a doctor” Consultation Description of issue(s) TGA consideration


· The Pharmacy Guild contends that ‘Prolonged period’ should be defined and that the advisory statement duplicates the intent of advisory statements 55 “Warning – Not for prolonged use”, 61 “Prolonged use without medical supervision can be harmful” and 62 “Prolonged use or excessive use without medical supervision could be harmful”

· The Pharmacy Guild proposes the consolidation of statements 55, 61, 62 & 207 with a more defined ‘prolonged period’ as well as inclusion of reference to seeking advice from both a pharmacist and a doctor.

· The TGA considers that the context in which statement 207 is placed on the label along with directions and recommended dose would allow consumers to determine an appropriate definition of prolonged use of coal tar. However, the TGA agrees that the advisory statement be amended to include reference to a pharmacist.

Outcome 1. Amend advisory statement 207 to “Do not use for prolonged periods except on the advice of a doctor or pharmacist”.

Advisory statement 208 “See your doctor before taking this product if you have high blood pressure or heart problems or are taking antidepressant medication”



· The Pharmacy Guild observes that consumers are as or more likely to receive advice from a pharmacist as a doctor (even for referral). In addition, if reference to antidepressants is specifically for MAO-Inhibitors which are not commonly used, this could be alarming for consumers taking more commonly used antidepressants such as SSRIs.

· The Pharmacy Guild recommends revising the statement into two parts for better clarification for consumer; “See your doctor or pharmacist before taking this product if you have high blood pressure or heart problems” and “Do not take if you are also taking the antidepressant medicines Phenelzine or Tranylcypromine.”

· The TGA agrees that the advisory statement 208 should be amended to include reference to a pharmacist.

· The TGA considers that interactions with antidepressants belonging to other therapeutic classes can also occur, therefore it would be inappropriate to amend advisory statement to specifically refer to Phenelzine or Tranylcypromine only.

Outcome 1. Amend advisory statement 208 to “See your doctor or pharmacist before taking this product if you have high blood pressure or heart problems or are taking antidepressant medication”

Histor

ical

doc

umen

t



Page 39 of 51

Advisory statement 209 “[This product/Product name] may cause sleeplessness if it is taken up to several hours before going to bed”



· CHF raises the concern that the advisory statement is not specific enough and should be revised to contain more detailed information. CHF proposes an indication of how long it will be before normal sleeping patterns resume should be provided as well as identifying a recommended time of day to use these products.

· The TGA does not agree with CHF that the advisory statement 209 should indicate how long it will be before normal sleeping patterns resume. The purpose of the advisory statement is to advise consumers that the product may cause sleeplessness if it is taken up to several hours before going to bed. Depending on the use of the product and individual’s reaction, it would be difficult to establish a suitable timeframe in which normal sleeping patterns would resume. In addition, as Pseudoephedrine can be included in cold and flu products which already generally have directions to take in the morning and in the afternoon, TGA considers that it would be redundant to include a recommended time of day to use the products in the advisory statement.

Outcome 1. Retain advisory statement 209 without amendment

Advisory statement 211 “Long term and repeated use should be avoided because darkening of the skin could occur”



· The Pharmacy Guild questions whether ‘long term’ use will be readily understood and suggests that a more defined terminology is used.

· The TGA notes the comment from Pharmacy Guild with respect to the understanding of the words “long term” by the consumers. Therefore to be consistent with words used in other similar advisory statements, the TGA agrees that the advisory statement 211 be amended. The TGA also considers that the context in which statement 211 is placed on the label along with directions and recommended dose would allow consumers to determine

Histor

ical

doc

umen

t



Page 40 of 51


an appropriate definition of prolonged use of hydroquinone.

Outcome 1. Amend advisory statement 211 to “Do not exceed recommended dose. Excessive or prolonged use should be avoided because darkening of the skin can occur”

Advisory statement 214 “Transient stinging or irritation may occur when using this product. If irritation persists, discontinue use”



· The Pharmacy Guild contends that the advisory statement 214 duplicates the intent of advisory statement 114 “Mild irritation may occur; stop use if it becomes severe”.

· The Pharmacy Guild recommends consolidation of advisory statement 114 and advisory statement 214 into one statement.

· The advisory statements are taken from ARGOM 2003 which set outs the requirements for warning statements in relation to the product based on the assessment by the TGA and Medicines Evaluation Committee.

· The TGA considers that the advisory statement 214 has a different intention to that of advisory statement 114 i.e. for advisory statement 214, consumers are warned that stinging and irritation that may occur are of a transient nature, and that if the irritation continues beyond the temporary period, they are advised to stop. Whereas, advisory statement 114 advises consumers to cease using if severe irritation occurs. In addition, a consolidated statement will result in an advisory statement that would be inappropriate for hydroquinone, which advisory statement 114 currently applies to. Therefore, the TGA does not agree that the advisory statement 114 and the advisory statement 214 can be consolidated

Outcome Not outcome action

Histor

ical

doc

umen

t



Page 41 of 51

Advisory statement 215 “May be irritant to the eyes (or words to that effect)”



· The Pharmacy Guild notes that the advisory statement duplicates the intent of advisory statements 79 “Avoid contact with eyes”, 80 “Do not use in the eyes”, 83 “Do not use near the eyes”, and 84 “Keep out of eyes”.

· The Pharmacy Guild proposes that these statements are consolidated into one “Keep out of eyes - may irritate”.

· The requirement for the advisory statement 215 is not to be implemented in this update (see Section 1: Application of advisory statement(s) to the medicine, Excipients).

Outcome 1. The advisory statement not to be implemented

Advisory statement 216 “Will irritate the eyes”



· The Pharmacy Guild points out that the advisory statement 216 is not referenced. · The TGA notes that this advisory statement was included in error.

Outcome 1. Remove advisory statement 216 from the RASML document

Advisory statement 217 “If skin irritation occurs, discontinue use and seek medical advice”



· The Pharmacy Guild asserts that “medical advice” may be confusing and is inconsistent with other terminology referring to doctor/pharmacist. Suggest replacement with doctor and/or pharmacist as appropriate

· The TGA agrees that the advisory statement 217 be amended to refer to a doctor or a pharmacist instead of “medical advice”.

Outcome 1. Amend advisory statement 217 to “If skin irritation occurs, discontinue use and seek advice from your doctor or pharmacist”

Histor

ical

doc

umen

t



Page 42 of 51

Advisory statement 218 “Not recommended for use on children and infants. Age needs to be defined – child could be anything from 2 years to 15 years”



· The Pharmacy Guild considers the advisory statement 218 duplicates the intent from other statements such as #2, #3, #4, #5, #6, #8 & #9

· At the time of assessment of advisory statements required for alpha hydroxy acids, there was no data to support a defined age group. Therefore, the TGA considers that it would not be appropriate to consolidate the advisory statement 218 with other advisory statements (#2, #3, #4, #5, #6, and #8) which specifies an age limit.

Outcome 1. Retain the advisory statement 218 without amendment.

Advisory statement 219 ‘If skin irritation occurs, discontinue use immediately’



· Both CHC and a sponsor notes that the advisory statement 219 is not consistent with the current ARGOM and MEC guidelines and recommends that it should be updated to ‘If skin irritation or rash occurs, discontinues use immediately’

· The TGA concurs with the proposal by CHC and the sponsor that the advisory statement should be consistent with the current ARGOM guidelines.

Outcome 1. Amend advisory statement 219 to “If skin irritation or rash occurs, discontinue use immediately “

Advisory statement 222 “Do not apply to infants under 12 months of age except on the advice of a doctor”



· The Pharmacy Guild observes that consumers are as or more likely to receive advice from a pharmacist as a doctor (even for referral).

· The TGA agrees that the advisory statement 222 should be amended to include reference to a pharmacist.

Histor

ical

doc

umen

t



Page 43 of 51


Outcome 1. Amend advisory statement 222 to “Do not apply to infants under 12months of age except on the advice of a doctor or pharmacist”.

Advisory statement 224 “This preparation should be used with caution on infants, small children and pregnant or lactating women”



· The Pharmacy Guild asserts that ‘Breast-feeding’ may be better understood than ‘lactating’

· The TGA agrees that the word “lactating” should be changed to “breast feeding”

Outcome 1. Amend advisory statement 222 to “This preparation should be used with caution on infants, small children and pregnant or breastfeeding women”.

Advisory statement 225 “Medical advice should be sought before use”



· The Pharmacy Guild questions whether the phrase ‘medical advice’ will be readily understood. The advisory statement 225 duplicates the intent of advisory statement 64 “Ask your doctor or pharmacist before taking” which is only used for astemizole & terfenadine which are proposed for archiving.

· The TGA agrees that advisory statement 64, which is only used for astemizole and terfenadine (which are proposed to be archived) should replace statement 225. However the advisory statement will need to be amended to also include the word “using” before it can be applied to Lindane.

Outcome 1. Amend advisory statement 64 to ‘Ask your doctor or pharmacist before taking/(or)(using)”. 2. Amend requirements for Lindane to “64, 224”

Histor

ical

doc

umen

t



Page 44 of 51

Advisory statement 229 “If symptoms persist, consult a doctor”



· The Pharmacy Guild observed that consumers are as or more likely to receive advice from a pharmacist as a doctor (even for referral). The Pharmacy Guild proposes amendment to “If symptoms persist, consult a doctor or pharmacist”.

· The TGA agrees with the Pharmacy Guild

Outcome 1. Amend advisory statement 229 to “If symptoms persist, consult a doctor or pharmacist”.”

Advisory statement 230 “Do not exceed the recommended dose. Excessive or prolonged use can be harmful”



· The Pharmacy Guild observes that ‘excessive’ and ‘prolonged’ may need greater definition in the advisory statement 230 and that it duplicates the intent of advisory statement 62 “Prolonged or excessive use without medical supervision could be harmful”

· The Pharmacy Guild recommends consolidating advisory statement 62 with the advisory statement 230 with greater definition for ‘excessive’ and ‘prolonged’. Or alternatively, consolidate & use with revised statement for duration (e.g. advisory statements 128 “Unless a doctor has told you to, do not use [this product/insert name of product] for more than a few days”, 144 “Do not take this medicine for longer than a few days at a time unless advised to by a doctor” or 160 “Do not use for more than a few days at a time unless a doctor has told you to. Do not exceed the recommended dose. Excessive use can be harmful”)

· The TGA does not agree that statement 62 and 230 can be consolidated. The purpose of statement 230 is to emphasise that consumers should not exceed the recommended dose for choline salicylate even in circumstances where there is medical supervision. Therefore, it would be inappropriate to use advisory statements 62 128, 144 and 160 which advises that the medicine can be used for longer periods when advised or under the supervision of the doctor.

· The TGA considers that the context in which statement 230 is placed on the label along with directions and recommended dose would allow the consumers to determine an appropriate definition of excessive and prolonged use of choline salicylate.

Outcome 1. Retain advisory statement 230 without amendment.

Histor

ical

doc

umen

t



Page 45 of 51

Revision of advisory statements



· The Pharmacy Guild notes the many inconsistencies in the terminology used in advisory statements and recommends revising the current statements to ensure consistency in terminology and using words that are more readily understood.

· The Pharmacy Guild proposes revision of a number of advisory statements (see submission) for consistency or better comprehension

· The Pharmacy Guild observed that a lot of statements refer the patient to the doctor if symptoms persist and asserts that pharmacists are the most accessible health professional for advice. Therefore it would be it would be more appropriate to refer consumers to the pharmacist as well as the doctor to facilitate health professional intervention. In addition, for serious matters, the pharmacist’s triage may facilitate earlier medical intervention.

· The Pharmacy Guild proposes a revision of referral options for a number of advisory statements (see submission) to include both the pharmacist and doctor

· The TGA notes the comments provided and proposal of the revision of advisory statements for consistency or better comprehension.

· Recommendations to revise advisory statements (198, 202, 204, 206, 207, 208, 217, 218, 222, 224 and 225) introduced in RASML 6 have been addressed elsewhere in this document. It should be noted that recommendations which require substantial amendments to advisory statements which are currently in use and were not introduced in RASML Update 6 consultation could not be considered and be acted upon as these were not part of the consultation. However, these comments have been noted down to be reviewed and considered for in future consultations for updating RASML.


Consolidating or archiving of advisory statements



· The Pharmacy Guild notes that there are a number of statements, both current and proposed, which appear to have a duplication of intent. The Pharmacy recommends reviewing current advisory statements and consideration of consolidating, revising or archiving as appropriate to streamline the list.

· It should be noted that recommendations which require amending advisory statements which are currently in use and were not introduced in RASML Update 6 consultation could not be given consideration as these were not part of the consultation. However, the TGA notes the merits of these comments and will consider the recommendations for inclusion in future consultations.

Histor

ical

doc

umen

t



Page 46 of 51


· TGA is mindful of the fact that, although there appears to be duplication due to similar wordings in the advisory statements, each of the advisory statements is applied to specific medicines in a specific context. Therefore consolidation of the advisory statements may result in the statement that is not applicable to some of the medicines that require the initial specific statement. In addition, the consolidated statement may be incompatible with other required advisory statements for that particular medicine.


Superseded advisory statements



· The Pharmacy Guild proposes that the following statements appear not to be referenced by any drugs and could be archived:

o #39 Warning – Can cause elevated blood pressure and interact adversely with other medication

o #45 This preparation should be part of an overall treatment plan regularly assessed with your doctor

o #104 Warning – Do not use on face or anal or genital areas o #42 Warning – Can react with other medicines appears to only be referenced by

astemizole & terfenadine which are being archived [Ref Section 6 of paper]. This statement could also be archived or revised.

o #68 is only referenced by hypericum. It could be archived & could be replaced by a revised #64

· The TGA does not agree that the advisory statements 45 or 104 can be archived as advisory statement 45 still applies to Ipratropium bromium, Salbutamol, Terbutaline; and advisory statement 104 applies to Podophyllin amd Podophyllotoxin.

· The TGA does not agree advisory statement 68 can archived until the next consultation when advisory statement 64 is proposed to replace advisory statement 68.

· However, the TGA agrees that the advisory statements 39, 42 can be archived as Astemizole, Terfenadine and medicines which are in Schedule 4 of the SUSMP are proposed to be archived.

Histor

ical

doc

umen

t



Page 47 of 51


Outcome 1. Advisory statements 39, 42 to be included in the archive section.

Histor

ical

doc

umen

t



Page 48 of 51

Section 3 – General comments Consultation Description of issue(s) TGA consideration


· ASMI suggests that broad consultation should occur when the need for an advisory statement is first perceived, rather than when it is a fait accompli.

· Where there are no safety concerns, ASMI members are requesting that the implementation period for existing periods be changed from a 12-month period to no longer than 24 months after the date of gazettal, or at least 24 months. This is mainly due to resources, costs and timeliness from labelling changes, especially for products manufactured overseas, where small changes may take at least 6-8 months, often longer.

· The TGA acknowledges that there would be a benefit in a formalised process of informing stakeholders of the introduction of new advisory statements when the need arises prior to the update of the RASML document.

· The TGA notes these comments for consideration but is of the opinion that, at this time, the RASML has sufficient lead-in times for transition to the new arrangements.

· In addition, there is a need to ensure that medicines labels are updated whenever new information about medicines that is essential for its safe and effective use comes to light.


· A sponsor asserts that the impact of the implementing the change will be costly, as the company will need to repack stock to meet the implementation deadline (of one year post gazettal). In addition, to include a warning on the carton that is already included in the enclosed package insert for the anticholinergic products, would be an unnecessary financial burden to the company.

· The TGA notes the comments from the sponsor with respect to the impact on the company. The TGA proposes to review the transition time frame to the new arrangements to assist in minimising the impact. However the TGA must also ensure that the TGA’s responsibility in ensuring the safety of products available to the public would not be compromised as a consequence of the extension of the transition time frame.

· It should be noted that to cover short-term contingencies the TGA does allow sponsors, where necessary, to over-stick labels (under GMP conditions) with newly required advisory statements.

· In addition, Section 14 exemptions are available for sponsors to apply for circumstances and particularly

Histor

ical

doc

umen

t



Page 49 of 51


for products with changes requiring approvable variation where printing of revised labels cannot commence until the TGA approval is received.


· Bayer supports a 2 years implementation timeline for any new or updated advisory statements. This will allow sufficient time to update ARTG entries and labelling as many globally sourced products have length lead time. Bayer also suggests that broad consultation to occur when the need for an advisory statement is first perceived, rather than when it is a fait accompli.

· ASMI in expressing their concerns with the practicality and the cost of implementing so many artwork changes in the space of one year proposes: 1. An extension of the transition time frame from 12 months to 18 months 2. Recognition that ASMI members will still need to apply for some Section 14

exemptions, particularly for products with changes requiring approvable variation where printing of revised labels cannot commence until the TGA approval is received.

3. Consideration of establishing a priority evaluation for RASML only approvable variations.

· The TGA notes the comments from Bayer and ASMI and are currently reviewing the request with respect to increasing transition time frame to the new arrangements. However the TGA must also ensure that the TGA’s responsibility in ensuring the safety of products available to the public would not be compromised as a consequence of the extension of the transition time frame. In addition, it is noted that most of the advisory statements in the consultation document are already currently being applied under the Listing Notices, ARGOM and ELF prior to the update of the current RASML document.

· Section 14 exemptions are available for sponsors to apply for circumstances and particularly for products with changes requiring approvable variation where printing of revised labels cannot commence until the TGA approval is received.

· The TGA acknowledges that there would be a benefit in a formalised process of informing stakeholders of the introduction of new advisory statements when the need arises prior to the update of the RASML document.

· The TGA hopes the proposal of a new process in updating RASML will address the issue that has been raised with respect to the consultation process.

· CHF recommends an inclusion of a guideline requiring all medicines labels to include clear directions for use. Both the directions for use and the advisory statements should

· The comments and recommendation from CHF regarding use of larger font size for advisory

Histor

ical

doc

umen

t



Page 50 of 51


be distinguished from the remainder of the label through the use of larger font size. Suggested that direction for twice daily should be “take one tablet in the morning and another one in the evening. Positive message such as taken on empty stomach.

statements and directions for use will be forwarded to the working group in the TGA who are undertaking a labelling and packaging review.

· The TGA also notes the comments with respect to the wording of direction of use, but proposes that this issue is separately addressed during the evaluation process.

Histor

ical

doc

umen

t

Therapeutic Goods Administration PO Box 100 Woden ACT 2606 Australia

Email: [email protected] Phone: 1800 020 653 Fax: 02 6232 8605 www.tga.gov.au

Histor

ical

doc

umen

t

required advisory statements for medicine labels updates ... · (excluding atropine methonitrate),...

Documents