Required Advisory Statements for Medicine Labels updates TGA response to submissions
Version 3.0, April 2012
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Historical
Therapeutic Goods Administration
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.
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Copyright © Commonwealth of Australia 2011 HistoricalThis 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
Required Advisory Statements for Medicine Labels updates: Page i TGA response to submissions, V2.0 November 2011
Therapeutic Goods Administration
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: OTCME 24 November 2011 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 outcomedocument 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 Historicalgrammatical errors were corrected
Required Advisory Statements for Medicine Labels updates: Page 1 of 51 TGA response to submissions, V2.0 November 2011
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V3.0 page 7 – Advisory statement 180 – Correction of statement OTCME 21 May 2012 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
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Required Advisory Statements for Medicine Labels updates: Page 2 of 51 TGA response to submissions, V2.0 November 2011
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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
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Required Advisory Statements for Medicine Labels updates: Page 3 of 51 TGA response to submissions, V2.0 November 2011
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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.
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 document 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 Historical5. Pharmacy Guild of Australia 6. Apotex Pty Ltd 7. Colgate-Palmolive (Australia) Pty Limited 8. Consumers Health Forum 9. Complementary Health Council
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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. 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.
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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 document
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.
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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 Pyridoxal, Pyridoxine, Pyridoxamine healthcare practitioner as soon as possible.
179 WARNING – Stop taking this medication if you experience tingling, burning or numbness and see your Pyridoxal, Pyridoxine, Pyridoxamine healthcare practitioner as soon as possible. Contains vitamin B6.
180 If the [condition/insert type of condition] persists after two days of treatment, seek medical advice as Anticholinergics, Atropa Belladona, Atropine Compounds, soon as possible. (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 Chitosan medication. document 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 Folic acid defect/spina bifida, seek specific medical advice.
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 Hydroxyanthracene derivatives pregnant or breast feeding, seek the advice of a healthcare professional before taking this product.
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
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No Advisory statement Medicines to which the statement will apply
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 documentPollen 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
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No Advisory statement Medicines to which the statement will apply
202 Unless a doctor has told you to, do not use [this product / product name] with other medicines that you Diclofenac, Ibuprofen, Indomethacin, Ketoprofen (dermal are taking regularly 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 Benzocaine Lignocaine lozenge professional.
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 Phenylephrine, Pseudoephedrine taking antidepressant medication. document
209 [This product/Product name] may cause sleeplessness if it is taken up to several hours before going to Phenylephrine, Pseudoephedrine bed.
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 Chlorhexidine occurs.
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
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No Advisory statement Medicines to which the statement will apply
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 Antihistamine including Diphenhydramine, Doxylamine, operate machinery. Avoid alcohol. Promethazine
222 Do not apply to infants under 12 months of age except on the advice of a doctor. documentCamphor
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 Lindane women.
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
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No Advisory statement Medicines to which the statement will apply
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
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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 document · 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
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Alphahydroxy acids (glycollic acid, lactic acid, citric acid and other fruit acids)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · ACCORD and another sponsor argues that the proposed warnings are inappropriate · The TGA acknowledges that low concentrations of AHAs (2011) for products containing alphahydroxy acids (AHA) in low concentrations, such as are used as buffers in certain formulations. Therefore when included for their buffering capacity. Therefore the advisory statements 194 & TGA agrees with the proposal that the advisory 195 should be confined to products that contain AHAs at sufficiently high statements 194, 195 213 and 214 will only be applied to concentrations, and in formulations that are designed to remove dead skin cells. those topical products which include alpha hydroxy acid Equally, the advisory statements 213 & 214 are formulation dependent and are only as active ingredients. appropriate for products with higher concentrations of AHAs and low pH. · However, TGA does not agree with limiting to the specific · ASMI further suggests that the advisory statements be applied only when alpha indication “to remove dead skin cells” as alpha hydroxy hydroxy acids are included as active ingredients and specifying the indication “when acid may be used to treat other conditions such as acne used in topical products to remove dead skin cells”. 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” document Anaesthetics, dermal (Amethocaine, Benzocaine, Cinchocaine, Lignocaine)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · Both a sponsor and ASMI point out that the advisory statement 205 is not currently · The TGA acknowledges that advisory statement 205 is (2011) required in the current Australian Regulatory Guideline for OTC Medicine (ARGOM not currently required in the current ARGOM 2003. 2003) but was newly introduced in the draft update of ARGOM which has not been However it is consistent with current practice during finalized. evaluation of applications and reflected in the draft update of ARGOM. Outcome 2. Retain the advisory statement 205 without amendment
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Anaesthetics, dermal (Amethocaine, Benzocaine, Lignocaine)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · ASMI raises the concern that the condition proposed for the RASML entry extends the · The TGA agrees with the suggestions put forward by (2011) requirement to both dermal and topical use whilst the draft update of ARGOM ASMI. 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. 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 exclusiondocument 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)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · A sponsor does not support the application of the advisory statement 205 to · The TGA notes the issue raised by the stakeholders with (2011) haemorrhoidal products, as these are used only on the rectal area and are sold with respect to confusion caused by advisory statement 205 applicators for use for internal haemorrhoids. The sponsor points out that inclusion for haemorrhoidal products. The TGA acknowledges that of the proposed warning on the pack would carry with it the implication that the the condition for Cinchocaine is incorrect and accepts the product might be able to be used on large areas and it might possibly cause confusion suggestion put forward by ASMI to rephrase the for consumers. condition · 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
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Consultation Description of issue(s) TGA consideration
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) Consultation Description of issue(s) documentTGA consideration RASML Update 5 · The Pharmacy Guild notes an inconsistency with other related products for diarrhoea · In relation to duration of use, the intent of advisory (2009) such as Loperamide or Diphenoxylate, both of which require RASML statement 17: statement 17 (in part) “Do not use beyond 48 hours... “Do not use beyond 48 hours or in pregnancy or lactating women except on doctor’s except on doctor’s advice” and 180 “If the condition advice.” Products containing Diphenoxylate also contain a small amount of Atropine persists after two days of treatment, seek medical advice sulphate, which has little therapeutic significance but is added to discourage as soon as possible” is the same. Thus, for combination excessive self-medication. These combination products will thus require both RASML products containing Diphenoxylate and Atropine which statements 17 - “Do not use beyond 48 hours or in pregnancy or lactating women will require both RASML statements 17 (for except on doctor’s advice”) for Diphenoxylate, and the warning statement “If the Diphenoxylate) and 180 (for Atropine), the products will condition persists after two days of treatment, seek medical advice as soon as possible” have complied with Required Advisory Statement for for Atropine. In this regard, the Guild suggests that it would be more appropriate to Medicine Labels (RASML). This is also consistent with have consistent labelling requirements for all Over the counter (OTC) the section on combination statements in the RASML antispasmodic/antidiarrhoeal products relating to duration of treatment and use document which states that “Where more than one during pregnancy and lactation. statement is required, they may be combined to form · With respect to use in pregnancy, the Guild highlights that Atropine and Hyoscine are simple sentences where appropriate, provided that the both classified as pregnancy Category A, Loperamide is Category B3 while intent of each of the statements is not changed and any
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Consultation Description of issue(s) TGA consideration
Diphenoxylate is Category C. Therefore the Pharmacy Guild suggests that all OTC additional requirements are also met.” antispasmodic/antidiarrhoeals should have the advisory statement “If the condition · In relation to use in pregnancy, the TGA notes that while persists after two days of treatment, seek medical advice as soon as possible”) and that Atropine and Hyoscine are both classified as pregnancy either RASML statement 15 (“Not recommended for use by pregnant or lactating Category A, Hyoscyamine is in Category B2. These three women”) or a new RASML in the manner of “Do not use during pregnancy or lactation substances currently do not have any advisory without the advice of your doctor or pharmacist” be used for Loperamide and statements. However, the current Australian Regulatory Diphenoxylate. 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 documentthat 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.
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Aspartame
Consultation Description of issue(s) TGA consideration
RASML Update 6 · ASMI questions the need for more stringent warning given that Aspartame is included · Given the known safety concerns related to use of (2011) in the first schedule of Therapeutic Goods Order (TGO) 69 which requires Aspartame particular substances by phenylketonurics, the TGA is of (and Phenylalanine) to be declared on label. Additionally, the Required Advisory the opinion that individuals with this condition would Statements for Medicine Labels (RASML 2008) currently states that unless otherwise want/need to be advised of all possible sources. specified in column 2 of the table in section 1, the requirements apply only if the · Electronic Listing Facility (ELF) has required that substance is included in the medicine as an active ingredient. As Aspartame is only products containing Aspartame (as active or excipient) used as an excipient in Over-the-counter and Listed medicines, and it is already include the advisory statement 193 since 2001. declared on labels, ASMI questions the entry in the consultation which has created a Therefore, the TGA is of the view that there has been no concern of whether the scope of RASML is changing. change in the requirements in relation to the use of this · ASMI suggests deleting the entry. 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. document· 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
Consultation Description of issue(s) TGA consideration
RASML Update 6 · ASMI notes the inappropriateness of including advisory statement 128 on products · The TGA agrees with ASMI that the advisory statement (2011) indicated for the prevention of cardiovascular disease or for the inhibition of platelet 128 would be inappropriate for products which are aggregation as these products are intended for longer term use for this indication. indicated solely for prevention of cardiovascular disease ASMI points out that it will create confusion for consumers to read that these or for the inhibition of platelet aggregation. 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
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Consultation Description of issue(s) TGA consideration
indicated exclusively for cardiovascular use is deleted. Outcome 1. Remove the requirement of statement 128 from Aspirin Entries 2, 3 and 4
Chlorhexidine
Consultation Description of issue(s) TGA consideration
RASML Update 5 · ASMI raises the concern that the recommendations by the MEC and the proposal to · The TGA considers that consumers should be adequately (2009) require advisory statements are not in accordance with NDPSC recommendations by advised to discontinue use if skin irritation is severe, and not including a 1% cut-off for Chlorhexidine products. ASMI also points out that the to rinse the product out of the eyes if necessary. The MEC NDPSC exempted solid dosage formulations of Chlorhexidine from the SUSMP on the did not recommend the inclusion of any cut-off basis that these formulations would not present an eye irritancy hazard to the user, percentage for the requirements of applying advisory and that the NDPSC did not recommend the need for warning statements for those statements, the TGA considers those susceptible to products in S5, S6 and S7. ASMI considers that the proposal to requiredocument advisory Chlorhexidine may experience skin/eye irritation statements 79, 85 and 114 should not apply to products containing <1% regardless of its concentration. Any topical products Chlorhexidine and requests the TGA to reconsider previous recommendations. containing Chlorhexidine, regardless of strength and use, · Bayer requests that further consideration of a cut-off level, i.e. 1% concentration may have the potential to cause irritation to the skin above which the advisory statements should apply, and that the appropriateness of and/or eyes (e.g. accidental contact with the eyes after each statement should also be considered against dosage form, strength and use. topical application of Chlorhexidine cream on the hands/fingers). Outcome 1. Retain current condition for Chlorhexidine
RASML Update 6 · Colgate Palmolive asserts that there are many mouth rinses/gels that contain · The record of decisions from the meetings of the NDPSC (2011) Chlorhexidine that are supplied in the Australian marketplace which are not has been published since 1999 and is available on the regulated as medicines, and these products would not be subject to any warnings TGA website. The decision made by NDPSC to include imposed by the Required Advisory Statements for Medicine Labels (RASML). Chlorhexidine in Schedule 7 of the SUSMP with a cut-off Therefore Colgate Palmolive advocates that risk assessment of Chlorhexidine when to Schedule 6 for preparations containing 7% or less, used in topical products should be the appropriate criteria for determining the use of Schedule 5 for 3% or less and an exemption to the warnings statements on labelling. unscheduled for 1% or less or when in solid
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
· Colgate Palmolive suggests that the SUSMP is the appropriate risk assessment preparations; was made on the basis of the potential for process for consideration of a warning statement for Chlorhexidine, as the SUSMP inhalational toxicity and severe eye irritancy. The NDPSC applies to all Chlorhexidine containing products with participation by the Industry for also “noted that Chlorhexidine was not listed in the consideration of any toxicologically supported concentration thresholds Required Advisory Statements for Medicine Labels · ACCORD asserts that the TGA’s proposal to apply advisory statements to (RASML). The NDPSC considered referring the issue of Chlorhexidine is inconsistent with international regulatory approaches, which are labelling of Chlorhexidine for human use to the OTC supported by expert reviews of the safety and toxicology of Chlorhexidine. For Section”. Consequently, advice was sought from the Chlorhexidine which is used in products that can be registered as a medicine, but also Medicines Evaluation Committee on appropriate sold as a consumer product (e.g. mouthwash) there has been no scientific justification advisory statements to be applied. RASML statements 79 for stating that all Chlorhexidine containing medicines will require mandatory “avoid contact with eyes” and 85 “if in eyes, rinse well statements, when these statements are not required for similar consumer products. with water” were proposed by MEC to be included in the In particular, cut-off percentages for the proposed labelling requirements have not RASML document. been provided. · At the same time, the MEC was advised of the Adverse · ACCORD also proposes that the SUSMP is the appropriate forum to evaluate the risk Drug Reactions Advisory Committee (ADRAC) review of assessment of Chlorhexidine when used in topical products to determine the reported adverse reactions to products containing appropriate criteria and cutoffs for warnings statements on labelling,document and Chlorhexidine. It was noted that the adverse reaction recommends TGA refer this substance to the scheduling process. reports did not distinguish a particular concentration of Chlorhexidine that resulted in adverse reactions · ASMI contends that the NDPSC did not recommend the need for warning statements, experienced. Consequently, the MEC did not recommend even for those Chlorhexidine products included in Schedules 5, 6 and 7. In addition, the inclusion of any cut-off percentage for the ASMI express concerns that the MEC’s recommendations and therefore the advisory requirement of applying advisory statements. 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 TGA considers those susceptible to Chlorhexidine the advisory statements for products containing < 1% Chlorhexidine are required. may experience skin/eye irritation regardless of its concentration. Any topical products containing · ASMI proposes changing the condition to “When included in topical products for Chlorhexidine, regardless of strength and use, may have human use containing 1% or more of Chlorhexidine.” the potential to cause irritation to the skin and/or eyes · ASMI suggest a separate line entry for requiring the new advisory statement 212, as it (e.g. accidental contact with the eyes after topical is only intended to apply to products used on mucosal surfaces. It is proposed that the application of Chlorhexidine cream on the new entry for Chlorhexidine have the condition set out as “When containing hands/fingers). Due to potential safety concerns, the TGA Chlorhexidine and included in preparations for topical use on mucosal surfaces.” considered that the advisory statements should apply to · ASMI further suggests that when the advisory statement 212 is required, then it may all topical products containing Chlorhexidine.
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
not be necessary to include advisory statement 114, as it is unreasonable to expect a · However, TGA agrees with the comments from ASMI and consumer to be able to differentiate between an ‘irritancy’ and an ‘allergic reaction’. the Pharmacy Guild that having both advisory statements Both advisory statements are very similar and both require treatment to stop in case 114 and 212 would be incongruous and lead to of a severe reaction. Therefore delete requirement for advisory statement 114. confusion. Therefore the TGA propose inclusion of a new · The Pharmacy guild notes that advisory statemet114 should not be needed with entry for products containing Chlorhexidine. advisory statement 212 and proposes that only advisory statement 212 be required for 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 Consultation Description of issue(s) documentTGA consideration
RASML Update 6 · Dr Ken Harvey submitted an article which raising his concern that both the old · The proposal that both the dose and duration of use for (2011) “stated dose” and the proposed “recommended dose” label warnings are ambiguous these products be better defined, relates specifically to and unhelpful. He proposes that both the dose and duration of use for these products the ambiguity of the recommended dose and duration of be better defined. 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
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Therapeutic Goods Administration
Decongestant, oral (Phenylephrine, Pseudoephedrine)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · ASMI points out that sponsors currently apply “May cause sleeplessness” to labels of · The TGA agrees with ASMI that the advisory statement (2011) Phenylephrine products and that Phenylephrine has an approximate 2.5 hour half life, 209 should only apply to Pseudoephedrine. Therefore a compared with a 6 hour half-life for Pseudoephedrine. Therefore ASMI contends that new statement is to be introduced to apply to products it is unnecessary to specify ‘up to several hours before going to bed’ as they are not containing Phenylephrine. 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”. 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, Stearyldocument dimethicone, Sucrose polycottonseedate) Consultation Description of issue(s) TGA consideration
RASML Update 6 · ACCORD would support the consideration of the substances proposed by TGA as eye · The advisory statements 79 and 215 are currently (2011) irritants to be assessed by the scheduling process, with the ACCS & ACMS to make incorporated in ELF as required statements for these recommendations on appropriate scheduling cutoffs, rather than RASML ingredients, and this has been the case since these implementing warnings for the list of substances proposed, without consideration of ingredients were approved for use in listed medicines. threshold limits below which no eye irritancy occurs. For those substances that · However, the concerns expressed in the consultation already have applicable schedule entries (e.g. quaternary ammonium compounds warrants further review by the TGA. Further comment on such as Stearamidopropyl PGdimonium chloride phosphate), ACCORD suggests that the toxicological assessment process for new topical RASML adopts the SUSMP entry. 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.
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Therapeutic Goods Administration
Fluorides
Consultation Description of issue(s) TGA consideration
RASML Update 6 · Colgate-Palmolive queries the justification for the new advisory statements for · The TGA considers the comments from the various (2011) Fluoride, which go beyond the SUSMP Fluoride entry requirements. stakeholders and agrees that the proposed condition text · ACCORD does not support the addition of new advisory statements for Fluoride was insufficient to differentiate Fluoride products which containing medicines which have not been justified from a risk perspective. ACCORD would require the warning statements. Therefore the believes that the SUSMP is the appropriate control mechanism for safety related TGA accepts the proposal from the sponsor and ASMI. 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 Fluoridedocument 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.
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
· 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
Consultation Description of issue(s) TGA consideration
RASML Update 5 · Bayer does not support the proposal that the advisory statement 183document be required for · The TGA considers it an appropriate advisory statement (2009) all non-prescription folic acid containing products as there is no need for OTC or for expectant mothers taking Folic acid supplement registered complementary medicines which require evaluation to carry the same medicines specifically indicated to reduce the risk of warning statements. spina bifida/neural tube defects, particularly if they have · Bayer recommends exemption be given to products that have undergone evaluation previously had a child with these conditions. The by the TGA 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
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Therapeutic Goods Administration
Hydrolysed milk protein - alpha casozepine enriched
Consultation Description of issue(s) TGA consideration
RASML Update 5 · CHC notes that the transition period for this substance should be amended to · The TGA agrees with CHC (2009) "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. Outcome 1. Transition period for this substance amended to “immediate”
Hypericum Perforatum
Consultation Description of issue(s) TGA consideration
RASML Update 5 · The Pharmacy Guild notes that consumers are as or more likely to receive advice · The TGA notes the merit of this recommendation and (2009) from a pharmacist as a doctor (even for referral), therefore proposes replacing propose consideration be given to presenting them for advisory statement 68 “Consult your doctor” with a revised advisorydocument statement 64 the next future consultation for updating RASML. Outcome No outcome action
Imidazoles (Butoconazole, Clotrimazole, Econazole, Miconazole, Oxiconazole, Tioconazole)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · Apotex notes that the advisory statement 75 refers patient to see a doctor or dentist. · It should be noted that advisory statement 75 applies to (2011) Apotex proposes removal of advisory statement 75 as OTC Clotrimazole not likely to imidazole fungal preparation, nystatin and triamcinolone. be used in any dental procedures and so would not be initiated by a dentist. Triamcinolone can be prescribed by dentist to treat · Bayer does not support the inclusion of RASML statement 13. Bayer argues that mouth ulcers. The advisory statement places the word vaginal candidiasis is a common infection during pregnancy leaving topical anti- “dentist” in brackets to indicate that sponsors have the fungal imidazoles the most common form of treatment during pregnancy. Therefore flexibility of removing reference to dentist if the product for Clotrimazole to be contraindicated in pregnant women would leave no other is not being used in dental procedures. Therefore the
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
efficacious medicines available to treat women during pregnancy. TGA does not agree that there is a need to remove · Bayer proposes that Schedule 3 imidazole vaginal products should not be required to advisory statement 75 have advisory statement 13 and to reinstate the requirement for advisory statement · The TGA concurs with the comments from the various 16 instead. stakeholders, and agrees with the proposal to remove the · ASMI shared similar concerns and does not support the new RASML statement 13 for requirement for advisory statement 13 to apply to the ingredients belonging to the imidazole class. Clotrimazole, Econazole and Miconazole; and to only apply advisory statement 16 to these ingredients. · 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. Outcome 1. Delete requirement for statement 13 for Clotrimazole, Econazole and Miconazole in vaginal preparation when included in Schedule 3 of the SUSMP. document 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)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · Roche comments on the inconsistency between the information in the SUSMP with · The TGA notes that the comments from Roche. As this (2011) respect to the NSAIDs which has the result of implying that some of the NSAIDs need relates to changes to the SUSMP, no further action is to comply with RASML even when scheduled in Schedule 4. E.g. Aspirin, Ibuprofen required. In addition, it should be noted that recent both require compliance with RASML in SUSMP Schedule 2 entry. Diclofenac, changes to the Therapeutic Goods Act has resulted in
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
Indomethacin and Naproxen does not require compliance with RASML in SUSMP RASML being only applicable to non prescription Schedule 2 entry. medicines. · Roche proposes that for clarity and consistency, the Schedule 2 SUSMP entry for all · The TGA is aware of the interaction of NSAIDs with NSAIDs that are also included in Schedule 4 should state “Compliant with the thiazide diurectics. However, as NSAIDS can potentially requirements of the RASML” which would preclude the medicines when packaged interact with many medicines, it may be inappropriate to and presented as prescription products from the requirements of RASML only single out thiazide diuretics. TGA considers that the · The Pharmaceutical Society of Australia (PSA) observes that due to interaction of proposal to amend advisory statement 149 “Unless a NSAIDs and thiazide diuretics, consideration should be given to including a statement doctor has told you to, do not use [this product/insert alerting consumers to see a doctor before taking an NSAID if they are being treated name of product] with medicines containing [insert name for high blood pressure or taking diuretics. of substance], aspirin, or other anti-inflammatory medicines or with medicines that you are taking · PSA propose that a new statement with additional cautionary wording be included. regularly” can address the issue of potential interactions Advisory statement 192 between NSAIDS and all other medicines. · A sponsor observes that the advisory statement 192 is not specific to children, nor Advisory statement 192 does it specify use as an analgesic therefore the sponsor believes it is unnecessarily document· The TGA agrees that the advisory statement 192 should broad. The sponsor also argues that it should not be a requirement to include this only be applied to NSAIDS which have paediatric doses warning on products containing ibuprofen that are indicated for cold and flu or sinus, and agrees to amend the wording of the statement to since these are usually used for short term relief of symptoms related to self limiting align with the Medsafe requirements colds or flu rather than pain. · However, the TGA does not agree that Flurbiprofen · 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 should be exempt from the requirement for advisory dehydration through diarrhoea and/or vomiting. Since children and babies are most statement 192. Although Flurbiprofen is available as a vulnerable to rapid dehydration due to their large surface area:volume ratio, the lozenge form for topical use to treat sore throats, it can sponsor believes that the Medsafe warning is more specific and adoption of the be swallowed orally and therefore have the same adverse Medsafe warning would also allow alignment with Australian/New Zealand labelling effects as other oral forms of NSAIDs. The argument put forward by ASMI regarding the unlikeliness that the · Therefore the sponsor suggests, in alignment with Medsafe requirements, the products will be used if already suffering from vomiting advisory statement 192 should apply only to ibuprofen products for use in children or diarrhoea or that it is difficult for consumer to and to analgesic products containing ibuprofen and to exclude cold & flu preparations determine if they are dehydrate also extends to other containing ibuprofen. oral forms of NSAIDs, therefore Flurbiprofen cannot be · In addition to not supporting the advisory statement to apply both adults and singled out as being unique to be exempt from the
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
children, ASMI further observes that wording of the warning does not provide requirement. guidance to consumers that vomiting and diarrhoea are examples of when they might Advisory statement 201 be dehydrated. ASMI queries a consumer’s ability to determine if they are dehydrated. · TGA considers the proposal put forward by ASMI to · ASMI notes that in New Zealand a similar statement is required on liquid amend the words “heart failure” to “heart problems” or preparations for paediatric use. ASMI believes that that the Medsafe wording for “heart conditions” would capture a much broader liquid paediatric products “Use of the medicine without a doctor’s advice is population and may exclude those patients who could contraindicated in children suffering dehydration through diarrhoea and/or otherwise take OTC NSAIDs. In addition, the advisory vomiting” is more helpful in explaining to consumers that vomiting and diarrhoea statement 201 is intended for those who have been may lead to dehydration. medically diagnosed with heart failure and would therefore recognise the term. Therefore TGA is of the · Therefore ASMI proposes that the advisory Statement 192 should be applied only to view that the original advisory statement is more paediatric dose products. The wording should be amended consistent with the more appropriate. However, RASML does allow that “wording consumer friendly Medsafe wording - “Ask your doctor or pharmacist before use of of the statements may be varied provided that the intent is the medicine in children suffering dehydration through diarrhoea and/or vomiting” not changed.”, therefore products which have advisory · In addition, ASMI does not consider that the advisory statement 192document is required for statements that uses the term “heart problems” would be lozenges containing Flurbiprofen, especially as the sugar in the product may in itself considered to be compliant with RASML and the labels cause diarrhoea. ASMI contends that it is unlikely the products will be used if already would not be required to be amended 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 Advisory statement 201 · 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
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
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
Consultation Description of issue(s) TGA consideration
RASML Update 5 · CHC recommends that the proposed condition “when included in non-prescription · The TGA agrees that amendment should be made to the (2009) medicines for oral ingestion” should be amended to apply only to products for oral condition to only apply to products for oral rehydration rehydration therapy. therapy Outcome 1. Amend condition to “ When included in Listed medicines for oraldocument rehydration therapy”
Proton pump Inhibitors (Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · PSA points out that the interaction of proton pump inhibitors (PPI) with Clopidogrel · TGA considers that it would be misleading if consumers (2011) should warrant consideration of inclusion of a warning statement to seek health are only warned about this particular interaction and not professional advice if using blood thinning medicines. 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. Outcome No outcome action
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Therapeutic Goods Administration
Psyllium
Consultation Description of issue(s) TGA consideration
RASML Update 5 · CHC notes that the advisory statement for Psyllium would include all Listed · The TGA agrees that the condition for Psyllium be (2009) medicines for oral ingestion, and should only apply to these products when they amended. provide a dose for children 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
Consultation Description of issue(s) TGA consideration
RASML Update 5 · A stakeholder expresses concerns that the statements would deter consumers from · The quantity restriction is an entry in the SUSMP. The (2009) using these products. He argues that there is research to support the use of vitamin TGA notes that the indications that the stakeholder B6 in a range of conditions. He states that the label warning should documentonly apply to referred to were not appropriate for Listed medicines. products that contain more than 100 mg of vitamin B6. Outcome 1. Retain condition.
Vasoconstrictor eye drops (Naphazoline, Phenylephrine, Tetrahydrozoline)
Consultation Description of issue(s) TGA consideration
RASML Update 6 · As for comments for Phenylephrine as a nasal decongestant ASMI queries the need · The TGA agrees with ASMI that Phenylephrine in topical (2011) for the advisory statement 209. preparations would not require advisory statement 209. · ASMI proposes the removal of the requirement for RASML statement 209 to apply to Phenylephrine Outcome 1. Remove requirement for statement 209 for eye drops containing Phenylephrine
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Therapeutic Goods Administration
Clarify ‘words to the effect’
Consultation Description of issue(s) TGA consideration
RASML Update 5 · ASMI seeks to clarify that “words to the effect’ were acceptable for all the proposed · In line with the requirements in the current RASML (2009) advisory statements. 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. Outcome No outcome action
Package Labelling
Consultation Description of issue(s) TGA consideration
RASML Update 5 · Bayer requests that due consideration be given to allow the requireddocument information · The TGA did not agree with the proposal to allow RASML (2009) from the five RASML statements be given the option to be either placed on the statements to be given the option to be either placed on product label or the patient information leaflets (PIL), noting that the definition or the product label or the patient information leaflet for the interpretation of ‘label’ is broader in the Act compared to that in the RASML following reasons: document or TGO69. Bayer considers that the option to allow RASML statements to - Inclusion of advisory statements on the outer label be placed in the PIL for S3 products can be legislatively supported. enables consumers, with the direct involvement of a · A sponsor notes that whilst many patients have access to pharmacists, it is well pharmacist, to make an informed decision in self- known that comprehensive information on these products, such as Consumer selecting an appropriate S3 medicine on their own, Medicine Information sheets, are not routinely given to patients with each purchase taking into account their pre-existing condition and or use. Therefore, for these products, the sponsor supports the implementation of the the advisory statements on the labels, and to use the advisory statement 180 for the primary packaging. However the sponsor believes medicine safely and effectively. that the advisory statement 180 should not be required for primary package labelling - Inclusion of advisory statements on the outer labels if products already contain this same warning in an enclosed Package Insert. The enables the consumer to read the necessary sponsor also argues that the current enclosed package inserts already include the information before they purchase the product. In the warning in bolded text in the first section, viz. "Always consult your doctor or case of the PIL, the consumer will not have access to pharmacist if pain does not improve within 48 hours or if pain worsens after treatment. the information until the product has been
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Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
· The sponsor proposes that the imposition of the warning should be restricted to purchased. those companies who do not include a registered package insert for their - Not all S3 products have PIL inserted in the pack. In anticholinergic medicines. Moreover for those Companies who have an enclosed practice, this would cause confusion if one brand of a registered Package Insert with this warning clearly included, be given the choice product with/without a PIL contains all the RASML about not including the additional warning on the primary packaging. 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. document· 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
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Therapeutic Goods Administration
Section 2: The wording of the advisory statement(s)
· Revised advisory statement 76 · Advisory statement 211 · Revised advisory statements 140 and 149 · Advisory statement 214 · Advisory statements 178 & 179 · Advisory statement 215 · Advisory statement 189 · Advisory statement 216 · Advisory statement 191 · Advisory statement 217 · Advisory statement 192 · Advisory statement 218 · Advisory statements 194 & 195 · Advisory statement 219 · Advisory statement 198 · Advisory statement 222 · Advisory statements 200 & 201 · Advisory statement 224 · Advisory statement 202 · Advisory statement 225 · Advisory statement 203 · Advisory statement 229 · Advisory statement 204 · Advisory statement 230 · Advisory statement 206 document· Revision of advisory statements · Advisory statement 207 · Consolidating or archiving of advisory statements · Advisory statement 208 · Superseded advisory statements · Advisory statement 209
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Therapeutic Goods Administration
Revised advisory statement 76 “If congestion persist for more than a few days, seek medical or pharmacist advice”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · ASMI states that they are aware that, as part of the registration process, products are · TGA agrees with the proposal that the current RASML (2011) required to include a precaution on using for more than a few days and rebound statement “If congestion persists, consult your doctor or congestion. However, ASMI contends that the change in wording of the current pharmacist” be maintained. advisory statement does not add anything useful. 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” Consultation Description of issue(s) documentTGA consideration RASML Update 6 · The Pharmacy Guild proposes that advisory statement 140 and advisory statement · Note: The TGA notes that the revised advisory statement (2011) 149 be consolidated and to also identify OTC anti-inflammatory. In addition, it should 140 in the consultation document should have read be noted that consumers are more likely to receive advice from pharmacist as from a “Unless a doctor has told you to, do not use [this doctor. product/insert name of product] with other medicines · The Pharmacy Guild proposes two separate statements: containing aspirin or other anti- inflammatory medicines or other medicines that you are taking regularly. 1. Adapted according to the contents: ‘Unless advised by your doctor or pharmacist, do not use [this product/insert name of product] with other · The TGA considers the consolidation of advisory medicines containing aspirin, ibuprofen, naproxen, diclofenac or mefenamic statement 140 and advisory statement 149 as acid [delete as appropriate] inappropriate due to advisory statement 140 being only 2. ‘Consult your pharmacist or doctor if you take other medicines regularly’. applicable to Aspirin only, whilst advisory statement 149 applies to the rest of the NSAIDS. However, TGA does · The Pharmaceutical Society of Australia (PSA) comments that the proposed new agree that each statement should be reworded to reduce wording for Statement 140 and 149 are unclear. It was noted that there were too the use of “other” and “medicines” as well as inclusion of many occurrences of “other” and “medicines” reference to a pharmacist. It should be noted that the RASML does allow “the wording of the statements may be
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Consultation Description of issue(s) TGA consideration
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”
Consultation Description of issue(s) TGA consideration
RASML Update 5 · The CHC proposes a warning statement similar to “WARNING – Exceeding the recommended · The TGA considers that the majority of (2009) daily dose of vitamin B6 may be harmful. Consult your healthcare practitioner for advice". consumers were unlikely to consult a · The Pharmacy Guild proposes the following alternative advisory statements:document healthcare practitioner before using a Listed
medicine and preferred the wording proposed For single ingredient products -“WARNING – This medication may be dangerous when used in o by the Pharmacy Guild. However, the large amounts or for a long period. Stop taking this medication if you experience tingling, Pharmacy Guild proposed statements would burning or numbness and see your healthcare practitioner as soon as possible” take up more space on a label than the o For multi-ingredient products -“WARNING – This product contains vitamin B6 which may be previous statements particularly if the product dangerous when used in large amounts or for a long period. Stop taking this medication if you is a multi-ingredient one. experience tingling, burning or numbness and see your healthcare practitioner as soon as possible" Outcome 2. Retain the advisory statements without amendment.
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Advisory statement 189 “This product may cause photosensitisation”
Consultation Description of issue(s) TGA consideration
RASML Update 5 · The Pharmacy Guild recommends that the advisory statement 189 ”This product may · In a review of the requirement for an advisory statement (2009) cause photosensitisation” be amended to "This product may make the skin extra to apply to Psoralea corylifolia, the TGA considers that it sensitive to sunlight - use appropriate precautions if exposed" or words to that effect. 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”
Consultation Description of issue(s) TGA consideration
RASML Update 5 · CHC recommends that the advisory statement 191 be amended as the wording ‘no · The advisory statement 191 cannot be altered due to it (2009) benefit’ is inaccurate. The CHC also considers clarification should be given between being a requirement as set out in Therapeutic Goods phytosterols and phytosterols ester dose limits. Wording similar to – ‘There is (Listing) Notice 2008 (No. 6). minimal benefit from taking more than 3g/day of phytosterols and document5g/day of phytosterols esters, from all sources’ would be more accurate. Outcome 1. Retain the advisory statement 191 without amendment
RASML Update 6 · A sponsor observes that he Listing Notice 2010 (No.1) does not include ‘For lowering · The TGA agrees, there was an error in the advisory (2011) cholesterol uptake’, therefore it should be removed from the advisory statement 191. statement 191 contained in the consultation document.
Outcome 1. Correction of advisory statement 191 to as per Listing Notice 2010 (No.1)
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Advisory statement 192 “Ask your doctor or pharmacist before use if you are dehydrated, or have diarrhoea or vomiting”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · A sponsor alludes to the requirement for a similar warning specifically on children’s · The TGA agrees that the advisory statement 192 should (2009) products by Medsafe. The Medsafe warning relates to children suffering dehydration only be applied to NSAIDS which have paediatric doses through diarrhoea and/or vomiting. Since children and babies are most vulnerable to and agrees to amend the wording of the statement to rapid dehydration due to their large surface area:volume ratio, the sponsor believes align with the Medsafe requirements (See Section 1: that the Medsafe warning is more specific and adoption of the Medsafe warning Application of advisory statement to medicines: Non would also allow alignment with Australian/New Zealand labelling. 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” document Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild contends that the advisory Statement 194 and advisory · The TGA does not agree that the advisory statements 70, (2011) statement 195 are duplications of advisory statement 70 “Avoid excessive exposure 93 and 194 can be consolidated at this time. Advisory to sunlight and other sources of ultra violet light” and advisory statement 93 statement 70 applies to orally ingested medicines which “Application to skin may increase sensitivity to sunlight” can cause photosensitivity whilst advisory statement 93 · The Pharmacy Guild recommends consolidating advisory statements 70, 93 & 194 and 194 applies to products for topical use. However for then using with advisory statement 195 as appropriate. ‘This product may make your consistency, the TGA considers that the advisory skin more sensitive to sunlight or other sources of UV light’ is proposed as the statement 194 should be amended to reflect the wording consolidated advisory statement. 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”.
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Advisory statement 198 “If diarrhoea persists seek medical advice”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild asserts that this may be confusing and is inconsistent with other · The advisory statement 198 is set out in accordance with (2011) terminology referring to doctor/pharmacist. Suggest replacement with doctor and/or the Listing Notice 2009 (No. 3), therefore it cannot be pharmacist as appropriate 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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild maintains that blood pressure may also be affected by NSAIDs · The TGA does not agree that the advisory statements 200 (2011) due to sodium & fluid retention from NSAID-induced reduction in glomerular and 201 can be substituted by advisory statement 166. filtration rate & renal blood flow. In addition, the Pharmacy Guild also notes that the The introduction of these statements is to advise those advisory statements 200 and 201 duplicates intention of advisory statementdocument 166 “If who have impaired kidney functions and heart failure to you have kidney disease or are taking heart or blood pressure medicine, consult your not use NSAIDS at all. Advisory statement 166 (which doctor or pharmacist before use. currently applies to Glucosamine and Potassium · The Pharmacy Guild proposes using the advisory statement 166 instead of the Chloride) advises the patient to consult a doctor or advisory statements 200 and 201. 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
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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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild observes that consumers are as or more likely to receive advice · The TGA agrees that the advisory statement 202 be (2011) from a pharmacist as a doctor. It would be more appropriate to refer consumers to amended to included reference to a pharmacist the pharmacist as well as the doctor to facilitate health professional intervention. 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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · CHF recommends that the advisory statement 203 should provide consumers with an · The TGA agrees with CHF. However there are no data to (2011) indication of how long they should refrain from eating or drinking hotdocument foods and indicate a quantifiable time that a person will need to beverages, as “soon after” is insufficiently specific. If it is not possible to provide this refrain from eating and drinking hot foods. Therefore, an information on the label, consumers should be advised to consult their doctor or alternative wording of the statement is provided. pharmacist. 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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild notes that the advisory statement duplicates the intent of · The TGA does not agree with the proposal to consolidate (2011) advisory statement 131 “Unless a doctor has told you to, do not use [this the statements. Although the advisory statement 204 product/insert name of product] in children 6 years of age or less” and advisory appears to be similar to advisory statement 113, it statement 150 “Do not use this [product/insert name of product] in children 6 years advises consumers that the anaesthetic lozenge may be
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Consultation Description of issue(s) TGA consideration
of age or less”. given on advice from a doctor, pharmacist or a dental · The Pharmacy Guild proposes that these advisory statements are consolidated and to professional. To amend statement 131 to include dental reference one only as well as using “dentist” instead of “dental professional”. 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” document Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild contends that ‘temporary use’ should be defined and that the · The TGA agrees with the Pharmacy Guild that statement (2011) advisory statement 206 duplicates the intent of advisory statement 128 “Unless a 206 should be amended to be more appropriately doctor has told you to, do not use [this product/insert name of product] for more defined. However, it would be inappropriate to than a few days at a time” and advisory statement 144 “Do not take this medicine for consolidate the advisory statement 206 with advisory longer than a few days at a time unless advised to by a doctor”. statements 128 and 144 as both these advisory · The Pharmacy Guild proposes the consolidation of the advisory statements 128, 144 statements are specifically applicable to medicines which & 206 to “This product is intended for short-term use only of [not more than a few differ from each other in safety profiles and has the days / or X days]”. Then use with advisory statement 226 “Prolonged use may be intention of advising that the consumers can take the harmful”. 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”
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Advisory statement 207 “Do not use for prolonged periods except on the advice of a doctor”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild contends that ‘Prolonged period’ should be defined and that the · The TGA considers that the context in which statement (2011) advisory statement duplicates the intent of advisory statements 55 “Warning – Not 207 is placed on the label along with directions and for prolonged use”, 61 “Prolonged use without medical supervision can be harmful” recommended dose would allow consumers to determine and 62 “Prolonged use or excessive use without medical supervision could be an appropriate definition of prolonged use of coal tar. harmful” However, the TGA agrees that the advisory statement be · The Pharmacy Guild proposes the consolidation of statements 55, 61, 62 & 207 with a amended to include reference to a pharmacist. more defined ‘prolonged period’ as well as inclusion of reference to seeking advice from both a pharmacist and a doctor. 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” document Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild observes that consumers are as or more likely to receive advice · The TGA agrees that the advisory statement 208 should (2011) from a pharmacist as a doctor (even for referral). In addition, if reference to be amended to include reference to a pharmacist. antidepressants is specifically for MAO-Inhibitors which are not commonly used, this · The TGA considers that interactions with antidepressants could be alarming for consumers taking more commonly used antidepressants such belonging to other therapeutic classes can also occur, as SSRIs. therefore it would be inappropriate to amend advisory · The Pharmacy Guild recommends revising the statement into two parts for better statement to specifically refer to Phenelzine or clarification for consumer; “See your doctor or pharmacist before taking this product Tranylcypromine only. if you have high blood pressure or heart problems” and “Do not take if you are also taking the antidepressant medicines Phenelzine or Tranylcypromine.” 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”
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Advisory statement 209 “[This product/Product name] may cause sleeplessness if it is taken up to several hours before going to bed”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · CHF raises the concern that the advisory statement is not specific enough and should · The TGA does not agree with CHF that the advisory (2011) be revised to contain more detailed information. CHF proposes an indication of how statement 209 should indicate how long it will be before long it will be before normal sleeping patterns resume should be provided as well as normal sleeping patterns resume. The purpose of the identifying a recommended time of day to use these products. 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 documentday 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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild questions whether ‘long term’ use will be readily understood and · The TGA notes the comment from Pharmacy Guild with (2011) suggests that a more defined terminology is used. 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
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Consultation Description of issue(s) TGA consideration
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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild contends that the advisory statement 214 duplicates the intent · The advisory statements are taken from ARGOM 2003 (2011) of advisory statement 114 “Mild irritation may occur; stop use if it becomes severe”. which set outs the requirements for warning statements · The Pharmacy Guild recommends consolidation of advisory statement 114 and in relation to the product based on the assessment by the advisory statement 214 into one statement. TGA and Medicines Evaluation Committee. · The TGA considers that the advisory statement 214 has a documentdifferent 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
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Advisory statement 215 “May be irritant to the eyes (or words to that effect)”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild notes that the advisory statement duplicates the intent of · The requirement for the advisory statement 215 is not to (2011) advisory statements 79 “Avoid contact with eyes”, 80 “Do not use in the eyes”, 83 “Do be implemented in this update (see Section 1: Application not use near the eyes”, and 84 “Keep out of eyes”. of advisory statement(s) to the medicine, Excipients). · The Pharmacy Guild proposes that these statements are consolidated into one “Keep out of eyes - may irritate”. Outcome 1. The advisory statement not to be implemented
Advisory statement 216 “Will irritate the eyes”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild points out that the advisory statement 216 is notdocument referenced. · The TGA notes that this advisory statement was included (2011) 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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild asserts that “medical advice” may be confusing and is · The TGA agrees that the advisory statement 217 be (2011) inconsistent with other terminology referring to doctor/pharmacist. Suggest amended to refer to a doctor or a pharmacist instead of replacement with doctor and/or pharmacist as appropriate “medical advice”. Outcome 1. Amend advisory statement 217 to “If skin irritation occurs, discontinue use and seek advice from your doctor or pharmacist”
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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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild considers the advisory statement 218 duplicates the intent from · At the time of assessment of advisory statements (2011) other statements such as #2, #3, #4, #5, #6, #8 & #9 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’ Consultation Description of issue(s) documentTGA consideration
RASML Update 6 · Both CHC and a sponsor notes that the advisory statement 219 is not consistent with · The TGA concurs with the proposal by CHC and the (2011) the current ARGOM and MEC guidelines and recommends that it should be updated to sponsor that the advisory statement should be consistent ‘If skin irritation or rash occurs, discontinues use immediately’ 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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild observes that consumers are as or more likely to receive advice · The TGA agrees that the advisory statement 222 should (2011) from a pharmacist as a doctor (even for referral). be amended to include reference to a pharmacist.
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Consultation Description of issue(s) TGA consideration
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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild asserts that ‘Breast-feeding’ may be better understood than · The TGA agrees that the word “lactating” should be (2011) ‘lactating’ 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” document Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild questions whether the phrase ‘medical advice’ will be readily · The TGA agrees that advisory statement 64, which is only (2011) understood. The advisory statement 225 duplicates the intent of advisory statement used for astemizole and terfenadine (which are proposed 64 “Ask your doctor or pharmacist before taking” which is only used for astemizole & to be archived) should replace statement 225. However terfenadine which are proposed for archiving. 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”
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Advisory statement 229 “If symptoms persist, consult a doctor”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild observed that consumers are as or more likely to receive advice · The TGA agrees with the Pharmacy Guild (2011) from a pharmacist as a doctor (even for referral). The Pharmacy Guild proposes amendment to “If symptoms persist, consult a doctor or pharmacist”. 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”
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild observes that ‘excessive’ and ‘prolonged’ may need greater · The TGA does not agree that statement 62 and 230 can (2011) definition in the advisory statement 230 and that it duplicates the intent of advisory be consolidated. The purpose of statement 230 is to statement 62 “Prolonged or excessive use without medical supervision could be emphasise that consumers should not exceed the harmful” documentrecommended dose for choline salicylate even in · The Pharmacy Guild recommends consolidating advisory statement 62 with the circumstances where there is medical supervision. advisory statement 230 with greater definition for ‘excessive’ and ‘prolonged’. Or Therefore, it would be inappropriate to use advisory alternatively, consolidate & use with revised statement for duration (e.g. advisory statements 62 128, 144 and 160 which advises that the statements 128 “Unless a doctor has told you to, do not use [this product/insert name medicine can be used for longer periods when advised or of product] for more than a few days”, 144 “Do not take this medicine for longer than under the supervision of the doctor. a few days at a time unless advised to by a doctor” or 160 “Do not use for more than a · The TGA considers that the context in which statement few days at a time unless a doctor has told you to. Do not exceed the recommended 230 is placed on the label along with directions and dose. Excessive use can be harmful”) 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.
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Revision of advisory statements
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild notes the many inconsistencies in the terminology used in · The TGA notes the comments provided and proposal of (2011) advisory statements and recommends revising the current statements to ensure the revision of advisory statements for consistency or consistency in terminology and using words that are more readily understood. better comprehension. · The Pharmacy Guild proposes revision of a number of advisory statements (see · Recommendations to revise advisory statements (198, submission) for consistency or better comprehension 202, 204, 206, 207, 208, 217, 218, 222, 224 and 225) · The Pharmacy Guild observed that a lot of statements refer the patient to the doctor if introduced in RASML 6 have been addressed elsewhere symptoms persist and asserts that pharmacists are the most accessible health in this document. It should be noted that professional for advice. Therefore it would be it would be more appropriate to refer recommendations which require substantial consumers to the pharmacist as well as the doctor to facilitate health professional amendments to advisory statements which are currently intervention. In addition, for serious matters, the pharmacist’s triage may facilitate in use and were not introduced in RASML Update 6 earlier medical intervention. consultation could not be considered and be acted upon as these were not part of the consultation. However, · The Pharmacy Guild proposes a revision of referral options for a number of advisory these comments have been noted down to be reviewed statements (see submission) to include both the pharmacist and doctor documentand considered for in future consultations for updating RASML. Outcome No outcome action
Consolidating or archiving of advisory statements
Consultation Description of issue(s) TGA consideration
RASML Update 6 · The Pharmacy Guild notes that there are a number of statements, both current and · It should be noted that recommendations which require (2011) proposed, which appear to have a duplication of intent. The Pharmacy recommends amending advisory statements which are currently in use reviewing current advisory statements and consideration of consolidating, revising or and were not introduced in RASML Update 6 consultation archiving as appropriate to streamline the list. 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.
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Consultation Description of issue(s) TGA consideration
· 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. Outcome No outcome action
Superseded advisory statements Consultation Description of issue(s) documentTGA consideration
RASML Update 6 · The Pharmacy Guild proposes that the following statements appear not to be referenced · The TGA does not agree that the advisory statements (2011) by any drugs and could be archived: 45 or 104 can be archived as advisory statement 45 o #39 Warning – Can cause elevated blood pressure and interact adversely with still applies to Ipratropium bromium, Salbutamol, other medication Terbutaline; and advisory statement 104 applies to o #45 This preparation should be part of an overall treatment plan regularly Podophyllin amd Podophyllotoxin. assessed with your doctor · The TGA does not agree advisory statement 68 can #104 Warning – Do not use on face or anal or genital areas o archived until the next consultation when advisory #42 Warning – Can react with other medicines appears to only be referenced by o statement 64 is proposed to replace advisory astemizole & terfenadine which are being archived [Ref Section 6 of paper]. This statement 68. statement could also be archived or revised. · However, the TGA agrees that the advisory o #68 is only referenced by hypericum. It could be archived & could be replaced by a revised #64 statements 39, 42 can be archived as Astemizole, Terfenadine and medicines which are in Schedule 4 of the SUSMP are proposed to be archived.
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Consultation Description of issue(s) TGA consideration
Outcome 1. Advisory statements 39, 42 to be included in the archive section.
document
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Section 3 – General comments
Consultation Description of issue(s) TGA consideration
RASML Update 5 · ASMI suggests that broad consultation should occur when the need for an advisory · The TGA acknowledges that there would be a benefit (2009) statement is first perceived, rather than when it is a fait accompli. in a formalised process of informing stakeholders of · Where there are no safety concerns, ASMI members are requesting that the the introduction of new advisory statements when the implementation period for existing periods be changed from a 12-month period to no need arises prior to the update of the RASML longer than 24 months after the date of gazettal, or at least 24 months. This is mainly due document. to resources, costs and timeliness from labelling changes, especially for products · The TGA notes these comments for consideration but manufactured overseas, where small changes may take at least 6-8 months, often longer. 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 documentuse comes to light. RASML Update 5 · A sponsor asserts that the impact of the implementing the change will be costly, as the · The TGA notes the comments from the sponsor with (2009) company will need to repack stock to meet the implementation deadline (of one year respect to the impact on the company. The TGA post gazettal). In addition, to include a warning on the carton that is already included in proposes to review the transition time frame to the the enclosed package insert for the anticholinergic products, would be an unnecessary new arrangements to assist in minimising the impact. financial burden to the company. 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
Required Advisory StatementsHistorical for Medicines Labels updates: Page 48 of 51 TGA response to submissions, V1.0 October 2011
Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
for products with changes requiring approvable variation where printing of revised labels cannot commence until the TGA approval is received. RASML Update 6 · Bayer supports a 2 years implementation timeline for any new or updated advisory · The TGA notes the comments from Bayer and ASMI (2011) statements. This will allow sufficient time to update ARTG entries and labelling as many and are currently reviewing the request with respect globally sourced products have length lead time. Bayer also suggests that broad to increasing transition time frame to the new consultation to occur when the need for an advisory statement is first perceived, rather arrangements. However the TGA must also ensure than when it is a fait accompli. that the TGA’s responsibility in ensuring the safety of · ASMI in expressing their concerns with the practicality and the cost of implementing so products available to the public would not be many artwork changes in the space of one year proposes: compromised as a consequence of the extension of the transition time frame. In addition, it is noted that 1. An extension of the transition time frame from 12 months to 18 months most of the advisory statements in the consultation 2. Recognition that ASMI members will still need to apply for some Section 14 document are already currently being applied under exemptions, particularly for products with changes requiring approvable variation the Listing Notices, ARGOM and ELF prior to the where printing of revised labels cannot commence until the TGA approval is update of the current RASML document. received. document · Section 14 exemptions are available for sponsors to 3. Consideration of establishing a priority evaluation for RASML only approvable apply for circumstances and particularly for products variations. 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 · The comments and recommendation from CHF clear directions for use. Both the directions for use and the advisory statements should regarding use of larger font size for advisory
Required Advisory StatementsHistorical for Medicines Labels updates: Page 49 of 51 TGA response to submissions, V1.0 October 2011
Therapeutic Goods Administration
Consultation Description of issue(s) TGA consideration
be distinguished from the remainder of the label through the use of larger font size. statements and directions for use will be forwarded to Suggested that direction for twice daily should be “take one tablet in the morning and the working group in the TGA who are undertaking a another one in the evening. Positive message such as taken on empty stomach. 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.
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Required Advisory StatementsHistorical for Medicines Labels updates: Page 50 of 51 TGA response to submissions, V1.0 October 2011
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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