CMEC 58

COMPLEMENTARY
MEDICINES
EVALUATION
COMMITTEE
E xtr acted R atified M inutes
F ifty-eighth M eeting
18 A ugust 2006
Abbreviations:
ADR
Adverse Drug Reaction
ADRAC
Adverse Drug Reactions Advisory Committee
ADRU
Adverse Drug Reactions Unit
AHS
Approved Herbal Substance
ANZTPA
Australia New Zealand Therapeutic Products Authority
ARGCM
Australian Regulatory Guidelines for Complementary Medicines
ARTG
Australian Register of Therapeutic Goods
BP
British Pharmacopeia
BW
Body Weight
CMEC
Complementary Medicines Evaluation Committee
DHA
Docosahexaenoic Acid
DOHA
Department of Health and Aging
EMEA
European Medicines Agency
EPA
Eicosapentaenoic Acid
ELF
Electronic Lodgement Facility
FSANZ
Food Standards Australia New Zealand
GMP
Good Manufacturing Practice
HDL
High Density Lipoprotein
IARC
International Agency on Research in Cancer
LDL
Low Density Lipoprotein
MDO
Managing Director’s Order
MEC
Medicines Evaluation Committee
MHRA
Medicines and Healthcare products Regulatory Agency

CMEC - Extracted Ratified Minutes

1

30 a. Members of CMEC present were: Professor Tony Smith (Chair) Professor Alan Bensoussan Professor Stephen Myers Professor Gillian Shenfield Associate Professor Douglas Moore Dr Vicki Kotsirilos Dr John Ryan Mr Kevin Ryan Present from the Therapeutic Goods Administration (TGA) were: Dr David Briggs Dr Rohan Hammett Dr John Hall Dr Andrea Hinschen Ms Michelle McLaughlin (afternoon session) Present as an expert advisor (for one item): Dr Susan James CMEC . Melbourne. to 3. from 9.m.NDPSC NHMRC NPS OCM OICG SCWA SUSDP TGA TMEC UK UV National Drugs and Poisons Schedule Committee National Health and Medical Research Council National Prescribing Service Office of Complementary Medicines OCM Industry Consultation Group Sugar Cane Wax Alcohols Standard for the Uniform Scheduling of Drugs and Poisons Therapeutic Goods Administration Traditional Medicines Evaluation Committee United Kingdom Ultraviolet The Complementary Medicines Evaluation Committee (CMEC) held its fifty-eighth meeting in the Mornington Room.m.Extracted Ratified Minutes 2 . Melbourne Airport. on Friday 9th June 2006.50 p. Hilton Hotel.

1. to ensure that all plant parts available for selection for a listable herbal species are relevant. R ecommendation 58. 3 GUIDELINES ON LEVELS AND KINDS OF EVIDENCE TO SUPPORT CLAIMS FOR THERAPEUTIC GOODS (GUIDELINES) CMEC did not consider any matters under this agenda item. CMEC . and are those on which a history of safe use of the plant has been based. 9 J une 2006). 4 JOINT AUSTRALIAN / NEW ZEALAND THERAPEUTIC PRODUCTS AGENCY MATTERS 4.H er bal mater ials with potential safety issues Background A TGA Officer introduced this item.1 Opening of M eeting The Chair opened the meeting at 9.1 Plant par ts pr oject .Extracted Ratified Minutes 3 .30 am and welcomed CMEC Members and TGA staff.4 C umulative index of issues consider ed at C M E C meetings Members noted the revised CMEC index.3 C onflict of I nter est Members submitted conflict of interest declarations specific to agenda items for this meeting to the Chair.1 PROCEDURAL MATTERS 1. CMEC Members were asked to review the regulatory status of a number of herbal species. ar e a tr ue and accur ate r ecor d of that meeting. and reminded Members that the basis for eligibility for many herbs in the list of permitted ingredients for use in Listed or "low-risk" medicines was a history of safe use.2 A pologies The CMEC Secretariat recorded the following apologies: Professor Bill Webster Associate Professor Heather Yeatman 1.1 C M E C confir ms that the dr aft M inutes of its pr evious meeting (C M E C 57. 2 CONFIRMATION OF MINUTES OF CMEC 57 (9 JUNE 2006) Members accepted. 1. without amendment. the minutes of the fifty-seventh meeting of CMEC as an accurate record of proceedings.

additional regulatory controls may need to be considered. if a batch came in within CMEC . equivalence. Members were advised of the proposed approach to the standardisation of herbal-derived ingredients which the OCM understands has been agreed to. particularly those commonly used in other traditional paradigms. 4. For example. at this point in time. However. based upon CMEC and OICG recommendations to date. the analytical range for the component is broad).Extracted Ratified Minutes 4 . this could result in a much more variable dose. if the expected herbal component range is 76-93mg. there was considerable discussion. However. on a number of previous occasions. and acceptable ranges for ingredients in medicines. and some disagreement on this matter. It is anticipated that this matter will be resolved at the next meeting of the OICG. quantification. and the OCM Industry Consultation Group (OICG). the Officer noted that if the amount of the herbal component in the product varies significantly (i. The Officer noted that recent discussions with industry have identified ‘acceptable ranges and limits for quantifying standardised ingredients’ as the main area of contention.2 Pr oposed appr oach to the standar disation of her bal-der ived ingr edients Background A TGA Officer noted that issues relating to standardisation of ingredients that have been extracted from herbal materials have been considered by both the CMEC. Members agreed that the OCM should determine meeting dates . In considering this paper. and the product is quantified with a 'not less than' value. This may have been partly due to the complexity of standardisation as an issue. Members further agreed that expertise in western herbal medicine and Ayurvedic herbs would be beneficial in reviewing the nominated herbs. in consultation with working group members. Discussion Members generally agreed that the issue of standardisation had been sufficiently considered by the CMEC on previous occasions. and the label states that a product contains 75mg of the component (the ‘not less than’ value). at the May OICG9 meeting. the TGA Officer advised Members that.2 C M E C r ecommends that a wor king gr oup be established to r eview the safety of cer tain her bal mater ials for continued use in L isted medicines. Discussion Members agreed that the formation of a herbal working party was the most appropriate strategy to manage this task. R ecommendation 58. in part.Members noted that for some herbal materials.e. ‘quantified by input’. The use of consistent analytical methods will assist consumers to better compare dosages in products. The TGA Officer explained that the proposed approach to standardisation was. analytical precision was raised as a potential area of concern.on an ‘as needs basis’. to ensure that quantification of herbal components is consistent industry-wide. and the overlap with several other herbal issues yet to be fully resolved such as naming.

4 I nfor mation sessions: Pr oposed r egulation of homoeopathic and anthr oposcophic medicines. Members noted that different solvents. anthroposophic and essence preparations. solvent concentrations and extraction methodology may result in preparations with different safety and efficacy profiles.htm 4. 4. These meetings provided an opportunity for individuals and groups to gain a more comprehensive understanding. including manufacturers.Extracted Ratified Minutes 5 . but also of the views held by other stakeholders. practitioners. should be permitted for extracts of the same herbal material. These monographs are the default standards for such ingredients when included in medicines supplied in Australia. may need to be revisited. the consumer would be receiving a considerably higher dose than is recorded on the label. permitted ingredients for products containing homoeopathic. evidentiary requirements to support indications and claims. not only of the proposed approach to the regulation of these products. Members considered numerous factors that could affect the equivalence of herbal extracts. CMEC Members were provided with an attachment. both in terms of composition as well as quantity of the native extract. and essences in the proposed Australia New Zealand joint regulatory scheme. and attended by a wide range of stakeholders. and to raise any other matters of concern. Members CMEC . and essences A TGA Officer advised the Committee that information sessions have recently been held in Auckland and Sydney. The TGA Officer also noted that the issue of acceptable limits for standardised ingredients. Members endorsed the proposed approach to the standardisation of herbal ingredients. when finalised. The Committee endorsed the guideline in its current form. consumer groups and educators. 4.5 H er bal mater ials with a B r itish Phar macopoeia monogr aph A TGA Officer asked the Committee to note that the current edition of the British Pharmacopoeia (BP) includes. which listed those monographs included in the current edition of the BP relating to herbal ingredients. Members noted that these sessions were well-received. to explain the proposed approach to the regulation of homoeopathic and anthroposophic medicines. Overall. sponsors.org/cm/0607pres-is-hae. particularly where due to inherent assay variability. will form an adjunct guideline to the Australian Regulatory Guidelines for Complementary Medicines (ARGCM). Attendees were given the opportunity to discuss issues of quality standards. This attachment also included a list of herbal substance (AHS) names that have been approved for use in medicines. a number of monographs which pertain to herbal preparations. and were asked to consider what variation. if any.3 E quivalence of extr acts: Dr aft guideline A TGA Officer noted that at CMEC 56 (April 2006). which.anztpa. including good manufacturing practice (GMP). or references. Members were requested to consider the draft guideline: Guidance on Equivalence of Herbal Extracts.limits at 93mg. Members noted that a copy of the meeting presentations is located on the Australia New Zealand Therapeutic Products Authority (ANZTPA) website at: http://www.

Reconfiguration of the fish oil starting material to create the material known as omega-3marine triglycerides occurs via hydrolysation of the fish oil. The TGA Officer also noted that earlier this year.Extracted Ratified Minutes 6 . The standard for omega-3-marine triglycerides specifies an eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content of not less than 45%. CMEC . Any ingredient that complies with the definition included in a BP monograph is required to meet the quality standards of that particular monograph. to ensure that the linked pharmacopoeial monograph for each AHS is appropriate. and these were outlined in the attachment.were reminded that the AHS name is a 'complete' name. which in turn outlines the permitted species. has a minimum omega-3 content of 28%. together with the associated AHS name. which includes a minimum EPA and DHA content of 22% (as per the adopted BP monograph of the same name). 5 ACTION ARISING FROM PREVIOUS MEETINGS: CMEC 57 CMEC considered several matters under this agenda item. which is characterised by a monograph in the British Pharmacopeia (BP). With the increase in the number of applicable BP monographs. from which the fatty acids are separated out. 6 EVALUATION OF NEW SUBSTANCES 6. Rich in Omega-3 Acids) presented as a 'For information' paper at CMEC 57. will be brought to the attention of stakeholders via the TGA website. they need to consume large amounts of fish oil. di and triglycerides and is essentially a reconstituted fish oil. Members were advised that once reviewed. the National Health and Medical Research Council (NHMRC) had recommended that Australians and New Zealanders increase their dietary intake of omega-3 fatty acids through the consumption of fish.1 Omega-3-mar ine tr iglycer ides Background A TGA Officer introduced the new substance. This has been a driving force for concentrating the omega-3 fatty acids. with a total omega-3 content of not less than 60%. which has found that in order for consumers to get the required dose of omega-3 fatty acids. this manufacturing process has had the added effect of eliminating some of the problems associated with fishy flavour and contaminants that are often found in fish products. The Committee was reminded that 'refined' or 'natural' fish oils (Fish oil. The omega-3 fatty acid content is concentrated by the removal of some of the other fatty acids and these are then re-esterified to form mainly triglycerides. The Officer indicated that this substance is comprised of a mixture of mono. which links to a pharmacopoeial monograph. In addition. some interesting overlaps have been created. The Officer indicated that there is increasing interest from industry in this growing worldwide market. plant part and preparation. Members were advised that a review of this overlap is required. Members were advised that in the past there was not always a relevant BP monograph with which to link an AHS name. the list of herbal preparations which are covered by a BP monograph. with the source of the fatty acids originating from the oil from a variety of families of fish.

Given the presence of an associated BP monograph. respectively in the briefing paper. They noted that this balance has formed the basis for many discussions on the particular benefits of these types of substances for people prone to coagulant arteriopathy. CMEC . another Member indicated that human cells already contain components of the oil (fatty acids) in their membrane and that this was different to the situation for other ingredients which. some of the concentrated fish oil products are already on the market. The TGA Officer indicated that the Committee may also wish to consider another option such as setting an upper limit on EPA and DHA content. are not naturally occurring constituents of human cells. On this basis. Nonetheless. and appears related to total dosage of omega-3 fatty acids. noting its defined monograph. few safety studies per se could be identified.A search of the ARTG by the TGA examining the fish oils currently on the market suggests that. Members were satisfied that this substance was adequately defined from a compositional point of view. One Member also considered the increased bleeding time at high doses may be related in part to the therapeutic response. Thus. they considered fish oil. on the basis of the EPA and DHA content. the biggest difficulty in the evaluation was determining the identity of the fish oil used in the study in order to make an informed safety assessment. despite the limited safety data. However. by comparison. The Member was concerned that if this substance was just fish. However. one Member considered whether it was worthwhile having a label warning to advise consumers against concomitantly having a fish rich diet. while the safety evaluation performed has raised some issues concerning increased bleeding time and effects on glycaemic control with high intakes of EPA and DHA. it was noted that sponsors may have difficulties meeting some of these specifications. Members noted the increased risk of bleeding and alteration of glycaemic control at high EPA and DHA doses. One Member suggested that it probably represented a balance between platelet aggregation and disaggregation prostaglandin. In response.mediated processes. Discussion Characterisation: Members were asked to consider whether this substance was adequately characterised. it would be unlikely that fish oil supplements would be taken if the diet was rich in fish. worldwide consumption and absence of remarkable safety concerns as reasons underlying this decision. a more favourable option for people taking fish oils compared to that currently available. despite the extensive global use of fish oils.Extracted Ratified Minutes 7 . Members voted unanimously in favour of option 1. The Committee was asked to consider whether the substance 'omega-3-marine triglycerides' was suitable or not for use as an ingredient in Listed Medicines as indicated by options 1 and 2. Members considered this evaluation part of an inevitable process in the emerging role for fish oils. Overall. Members considered that the increased bleeding was likely related to a prostaglandin-mediated process. The Officer noted that while there was such a vast amount of available literature on fish oils. Safety: Members considered the critical issue was that of safety and risk of toxicity. this is likely to occur regardless of the source of the oil. Members came to the view that there were no safety concerns with this substance. generally the whole fish would be consumed whereas there are significant modifications to the oil occurring. considering omega-3-marine triglycerides suitable for use as an ingredient in Listed Medicines. in the form omega-3-marine triglycerides.

The TGA commissioned a consultancy to address these issues and to update an earlier 1998 detailed review of chemistry. which included their regulatory history and recent developments surrounding their regulatory status. In December 2005. as well as products to aid slimming. and • regarding the adoption or need for amendment of the draft Guidelines developed in 1998. A TGA Officer provided an overview of these products. had previously looked at the regulation of these substances after concerns that there were no consistent labelling rules about potential problems associated with their use.R ecommendation 58. Hydroxyanthracene derivatives are present in herbs including Senna.e. pharmacology and pharmacokinetics. Rhubarb and Buckthorn. The Committee was also being asked. CMEC .1 H ydr oxyanthr acene der ivatives Background CMEC was asked to advise the TGA on the safety of hydroxyanthracene derivatives as supplied in complementary medicines and whether there was any need for a change to the way they are currently regulated. Aloe. CMEC and its predecessor committee. depending on the outcome of these discussions. the Traditional Medicines Evaluation Committee (TMEC). to endorse the Draft Guidelines developed by the OCM for these substances. but CMEC were concerned about the safety associated with prolonged use and abuse potential of these products.2 CMEC considered one matter under this agenda item. 7 SAFETY OR EFFICACY REVIEWS 7. however it is important to note that the principles of these guidelines form the essence of the electronic lodgement facility (ELF) rules which apply to products going on to the ARTG as Listed medicines. • on how these products should be supplied and regulated in the future. Cascara.Extracted Ratified Minutes 8 . particularly when used other than as laxatives (i.3 C M E C r ecommends to the T G A that omega-3-mar ine tr iglycer ides (B r itish Phar macopoeia) is suitable for use as an ingr edient in or al L isted medicines. Frangula. slimming products). and the acceptable time limit that these products could be used and therefore recommended that an updated safety review be conducted to allow them to make recommendations: • on their continued suitability for use in Listed medicines. They act as stimulant laxatives and are present in many Listed products including those indicated for constipation. 6. Draft Guidelines were prepared but never finalised or incorporated into the TGA legislation. the TGA requested the Committee’s comments and endorsement of these guidelines.

CMEC . pregnancy and lactation. or habituation/tolerance. which must comply with the ELF rules reflected in the draft Guidelines currently awaiting CMEC endorsement. cathartic colon. while some evidence or argument has been published since 1998 suggesting that there may not be an association between hydroxyanthracene derivative laxatives and either colorectal carcinoma.This review found that there was very little information available regarding the acute or subacute toxicity of hydroxyanthracene derivatives. The Report that has been prepared summarises the range of regulatory approaches taken by other countries to these substances which vary from no regulation to requiring advisory statements and setting dose limits. The Committee was asked to consider the following options: • to recommend to the TGA that hydroxyanthracene derivatives continue to be permitted for use in Listed Medicines providing they comply with the current ELF rules based on the draft guidelines. Discussion Study quality . Animal studies have not shown an increase in carcinogenicity after Senna administration. and sometimes demonstrating an apparent protective effect against genotoxicity. The overall genotoxicity of herbal preparations containing hydroxyanthracene derivatives appears complex. much the same as the ELF and the draft Guidelines require. habituation/tolerance or colorectal carcinoma. Standard animal carcinogenicity studies have not been conducted on other anthranoid laxatives. However. and tumour promotion studies have demonstrated conflicting results. In addition. or • to recommend tighter controls for these substances to the TGA. They considered that the various sorts of studies.confounding factors and evaluation outcomes: Members noted that their attention was focussed on the studies performed since 1998. the data have not confirmed the suggested association between hydroxyanthracene laxatives and cathartic colon. However. There are currently over 400 products listed on the ARTG for oral use that contain one or more of the anthranoid-containing herbs. gave a range of different answers and that there was not a clear case for a causal relationship. however. such as case controls. There was very little evidence on the effects of anthranoid laxatives on fertility. even though there was some suggestion of increased colorectal cancer risk with hydroxyanthracene derivatives. with particular interest in the relationship between hydroxyanthracenes and colorectal cancer. The clinical data available since 1998 has not revealed any previously unidentified adverse events associated with the acute or chronic use of hydroxyanthracene derivatives. with the preparations sometimes demonstrating greater genotoxicity than the purified chemicals. these substances are no longer present in any of the hydroxyanthracene products sold in Australia. Herbal preparations containing hydroxyanthracene derivatives are contained in laxative preparations as well as diet aids and more general herbal supplements. but danthron (1. the overall body of data published to date does not conclusively confirm or refute the associations. and • to consider whether they wished to adopt the draft Guidelines for incorporation into the Australian Regulatory Guidelines for Complementary Medicines (ARGCM). cohort analyses etc. there does not seem to be any evidence to suggest specific concerns.Extracted Ratified Minutes 9 .8-hydroxyanthraquinone) and l-hydroxyanthraquinone have been shown to be carcinogenic in animals.

and that if these substances are going to be used. Label warnings . as they would with any stimulant laxative. The Member indicated that they were inclined to support use of a warning statement about the long-term use of hydroxyanthracenes. A Member noted the current ELF warning label which states "Drink plenty of water” and commented that a consumer might interpret this statement to mean to drink plenty of water with the medicine. and if the studies were not restricted to hydroxyanthracenes. It was also noted that the International Agency on Research in Cancer (IARC) examined the carcinogenicity of these substances in 2002 and had concluded there was insufficient evidence to make a definitive recommendation. A Member commented favourably on the succinct labelling requirements taken by both the Swiss regulator ("Long-term regular use of stimulant laxatives is generally to be avoided. they should only be used short-term. which lists the current label warnings applicable in ELF for anthranoid laxatives. A Member noted that commonly used products such as detoxification preparations and slimming agents contain stimulant laxatives and that it was important for consumers to be aware that they were taking stimulant laxatives. CMEC . it was very difficult to claim that hydroxyanthracenes are the cause of any identified problems. The Member considered that what the statement was really trying to say was that not drinking enough water is the most common cause of constipation in the community and that this in itself.needs and current warnings: A Member noted a patient they had seen had developed melanosis coli following consumption of aloe vera juice for many years for the treatment of chronic constipation. Members further noted considerable differences in the quality of the studies performed. the substance actually being examined. A Member queried whether there were currently any label warnings for these substances. in addition to the confounding factors inherent in these studies. and who had not realised that there may be consequences associated with long-term use. It was noted that laxatives are a very large group of substances. The Officer referred Members to page 59 of the evaluation report.Extracted Ratified Minutes 10 . more importantly. the absence of long-term safety data suggests erring on the side of caution. A TGA Officer noted that while available data suggests these substances are safe. The biggest problem identified in these studies was distinguishing causes of the constipation from the effects of the medicines used. This was considered an argument in support of labelling with wording suggested such as "These substances are known to have a stimulant effect on the bowel". as this can lead to habituation and increased hypoactivity of the intestines. The studies had not adequately examined the effects of hydroxyanthracenes and had often failed to adequately account for confounding factors. there was insufficient data for a consistent picture to emerge from which a clear recommendation for regulatory change could be made. while some looked at constipation and laxatives. A TGA Officer confirmed there were but that they did not contain advice about duration of use.") and the EMEA ("For short term use in cases of occasional constipation"). Some studies examined the effects of laxatives overall (were not restricted to just hydroxyanthracenes or stimulant laxatives). Overall. may be alternative to taking the preparation.Members acknowledged that there were not just problems with the different types of studies performed but.

they cannot really know whether they should be changed or not. Members were in favour of limiting the treatment duration in some way and several Members considered 2 weeks a reasonable maximum duration.focus groups: Two Members indicated that they would like to see the formation of focus groups to test the consumer understanding of warning statements. Few new conclusions could be drawn from the current safety review and no major safety concerns were identified that would necessitate the need for regulatory intervention. namely: F or all pr oducts making a laxative claim and with a daily dose of 10 mg or mor e der ived fr om hydr oxyanthr acene der ivatives: ‘ Dr ink plenty of water ’ (or wor ds to that effect) ‘ Pr olonged use may cause ser ious bowel pr oblems’ (or wor ds to that effect) CMEC .Extracted Ratified Minutes 11 . while single chemical entity type stimulant laxatives are sold only in pharmacies in New Zealand. The majority of Members favoured recommending that hydroxyanthracene derivatives continue to be permitted for use in Listed medicines.1 T hat existing r egulator y ar r angements for ingr edients used in L isted medicines that contain hydr oxyanthr acene der ivatives ar e appr opr iate. The Committee considered the key issue in deciding this was whether there was sufficient scientific evidence to support any recommended duration of use. such as "Prolonged use may cause serious bowel problems". Members also endorsed adoption of the draft guidelines. in much the same way other European agencies had done. having considered a safety review of ingredients permitted in Listed medicines that contain hydroxyanthracene derivatives. They were further concerned that the term "prolonged-use" could be widely interpreted and there was no indication how statements like these were being perceived by consumers.maximum duration: A Member queried how the maximum duration of 14 days was chosen by the Swiss regulator for its label warning statement and suspected that this was an arbitrary figure. One Member suggested use of an alternative statement such as "For intermittent use only" or "Not for long-term use". While the Committee favoured limiting the maximum treatment duration to avoid prolonged use.5. without any new regulatory or label warning changes. They considered that until the Committee is able to get some idea of what consumers understand of these statements. Alignment with New Zealand: A Member queried how these products were aligned with New Zealand. Label warnings . herbal-type products such as those containing anthranoid compounds are sold as dietary supplements and are currently unregulated. including the cur r ent labelling r equir ements. the Committee felt that there was fairly compelling evidence for not changing the way hydroxyanthracene derivatives are currently regulated.Label warnings . A TGA Officer indicated that. CMEC. they did not feel justified in setting a figure without supporting scientific data. Overall. made the following recommendations to the TGA: R ecommendation 58.

R ecommendation 58.’ (or wor ds to that effect) ‘ Use in childr en under 12 year s is not r ecommended’ ‘ I f symptoms per sist consult your health car e pr actitioner ’ (or wor ds to that effect) F or all pr oducts NOT making a laxative claim and with a daily dose of 10 mg or mor e der ived fr om hydr oxyanthr acene der ivatives: ‘ Pr olonged use may cause ser ious bowel pr oblems’ (or wor ds to that effect) ‘ Do not use when abdominal pain. I f you ar e pr egnant or br east feeding. or if you develop diar r hoea.’ ‘ Use in childr en under 12 year s is not r ecommended’ ‘ I f symptoms per sist consult your health car e pr actitioner ’ (or wor ds to that effect) F or all pr oducts making a laxative claim and with a daily dose of less than 10 mg der ived fr om hydr oxyanthr acene der ivatives: ‘ Dr ink plenty of water ’ (or wor ds to that effect) ‘ Pr olonged use may cause ser ious bowel pr oblems’ (or wor ds to that effect) ‘ Use in childr en under 12 year s is not r ecommended’ ‘ I f symptoms per sist consult your health car e pr actitioner ’ (or wor ds to that effect) F or all pr oducts NOT making a laxative claim and with a daily dose of less than 10 mg der ived fr om hydr oxyanthr acene der ivatives: L abel war nings as r equir ed by other ingr edients in the pr oduct.5. I f you ar e pr egnant or br east feeding.‘ Do not use when abdominal pain. seek health pr actitioner advice befor e taking this pr oduct. seek health pr actitioner advice befor e taking this pr oduct. nausea or vomiting ar e pr esent.’ (or wor ds to that effect) ‘ T his pr oduct may have a laxative effect’ ‘ T his pr oduct contains [name of her b(s) or chemical component(s)]. or if you develop diar r hoea. CMEC .2 T hat T he G uidelines for Or al Pr oducts C ontaining H ydr oxyanthr acene Der ivatives be incor por ated into the A ustr alian R egulator y G uidelines for C omplementar y M edicines (A R G C M ) as an adjunct guideline.Extracted Ratified Minutes 12 . nausea or vomiting ar e pr esent. 8 REGISTRATION APPLICATIONS CMEC did not consider any matters under this agenda item.

and the other.1 A dver se Dr ug R eactions A dvisor y C ommittee (A DR A C ) M eeting 293 A CMEC Member introduced this item to the Committee. CMEC . a vitamin E paper. Complementary medicine issues The Member outlined complementary medicines issues of interest. Members noted the adverse drug reaction reports involving complementary medicines from the 293rd meeting of ADRAC. which were limited to two published papers.9 VARIATION TO A REGISTERED PRODUCT CMEC did not consider any matters under this agenda item. which was briefly discussed. 10. Members also noted the most recent ADRAC bulletin. one a single case report of warfarin interactions with Matricaria chamomilla. Case reports Members also discussed current case reports and updates on previous case reports in detail.3 CMEC considered one matter under this agenda item. 10. 10 MATTERS REFERRED FROM WITHIN TGA 10. Details on the use of the herb were provided in the papers given to Members.1 Safety concer ns for Polygonum multiflor um Background A TGA Officer introduced this item advising Members that this matter would be considered by ADRAC at its next meeting. the TGA counterpart in the UK. The ADRU has received only one adverse reaction relating to P.2 CMEC considered one matter under this agenda item. with a welldocumented use in traditional Chinese medicine as a liver and kidney tonic. multiflorum on the ARTG with seven products containing P. multiflorum as the sole active. multiflorum in a 46 year-old female and the symptoms were suggestive of acute hepatitis. the Medicines and Healthcare products Regulatory Agency (MHRA). Members were advised that after receiving seven suspected hepatic adverse reaction reports associated with Polygonum multiflorum. 11 FOR INFORMATION 11. The Officer noted that there are 79 products containing P. which was noted.Extracted Ratified Minutes 13 . posted a safety alert on its website.

Extracted Ratified Minutes 14 . Another Member queried whether any other Members had prescribed this substance. all black cohosh products should have this warning.H er bal mater ials with potential safety issues Recommendation 58.There are also reports of 8 cases of hepatotoxicity with one or other forms of the herb in the published literature and no further literature was able to be sourced by an independent search conducted by the TGA Library. 12 SPONSOR REPRESENTATIONS TO CMEC CMEC did not consider any matters under this agenda item. a Member indicated that this was a commonly used and widely available herb and that it was among the top 40 commonly used Chinese herbs.2 CMEC . CMEC was asked to note the MHRA action and the fact that the ADRAC will pick the issue up at its next meeting in September. I tem 4. 14 RECOMMENDATION RECORD I tem 2 C onfir mation of Dr aft M inutes of C M E C 57 (9 J une 2006) Recommendation 58. after reviewing the safety of black cohosh. As of February this year. recommended that a warning statement be included in product labelling advising patients of the risk of liver toxicity. all new black cohosh products will be required to have the warning statement with a 12 month compliance period given to all other products.2 A TGA Officer reminded Members that both the CMEC and ADRAC.1 Plant par t pr oject . 9 June 2006). are a true and accurate record of that meeting. In response. By early 2007. Members were asked to note that sponsors of all black cohosh products were told of the new labelling requirement in February this year and that legislation had now been put in place to mandate this. Discussion Several Members queried whether the results of the ADRAC deliberations on this issue would be fed back to the Committee and a TGA Officer confirmed this would be the case. Members noted this item. E ur opean M edicines A gency (E M E A ) stance on pr oducts containing C imicifugae r acemosus r hizhome (black cohosh.1 CMEC confirms that the draft Minutes of its previous meeting (CMEC 57. They also commented on the relatively few cases of reported ADRs relative to its high usage. 13 OTHER BUSINESS CMEC did not consider any matters under this agenda item. r oot) 11.

O mega-3-mar ine tr iglycer ides Recommendation 58. including the current labelling requirements. If you are pregnant or breast feeding.1 E valuation of New Substances .1 Safety or E fficacy R eviews . I tem 7.H ydr oxyanthr acene der ivatives CMEC.CMEC recommends that a working group be established to review the safety of certain herbal materials for continued use in Listed medicines. or if you develop diarrhoea. makes the following recommendations to the TGA: Recommendation 58. nausea or vomiting are present. I tem 6. seek health practitioner advice before taking this product.’ (or words to that effect) ‘Use in children under 12 years is not recommended’ ‘If symptoms persist consult your health care practitioner’ (or words to that effect) For all products NOT making a laxative claim and with a daily dose of 10 mg or more derived from hydroxyanthracene derivatives: ‘Prolonged use may cause serious bowel problems’ (or words to that effect) ‘Do not use when abdominal pain. If you are pregnant or breast feeding.1 That existing regulatory arrangements for ingredients used in Listed medicines that contain hydroxyanthracene derivatives are appropriate. nausea or vomiting are present.5.3 CMEC recommends to the TGA that omega-3-marine triglycerides (British Pharmacopoeia) is suitable for use as an ingredient in oral Listed medicines.’ (or words to that effect) ‘This product may have a laxative effect’ ‘This product contains [name of herb(s) or chemical component(s)]. namely: For all products making a laxative claim and with a daily dose of 10 mg or more derived from hydroxyanthracene derivatives: ‘Drink plenty of water’ (or words to that effect) ‘Prolonged use may cause serious bowel problems’ (or words to that effect) ‘Do not use when abdominal pain.’ ‘Use in children under 12 years is not recommended’ ‘If symptoms persist consult your health care practitioner’ (or words to that effect) For all products making a laxative claim and with a daily dose of less than 10 mg derived from hydroxyanthracene derivatives: ‘Drink plenty of water’ (or words to that effect) ‘Prolonged use may cause serious bowel problems’ (or words to that effect) CMEC .Extracted Ratified Minutes 15 . having considered a safety review of ingredients permitted in Listed medicines that contain hydroxyanthracene derivatives. seek health practitioner advice before taking this product. or if you develop diarrhoea.

Recommendation 58. The Chair closed the meeting at 3:50 pm.2 That The Guidelines for Oral Products Containing Hydroxyanthracene Derivatives be incorporated into the Australian Regulatory Guidelines for Complementary Medicines (ARGCM) as an adjunct guideline.‘Use in children under 12 years is not recommended’ ‘If symptoms persist consult your health care practitioner’ (or words to that effect) For all products NOT making a laxative claim and with a daily dose of less than 10 mg derived from hydroxyanthracene derivatives: Label warnings as required by other ingredients in the product. CMEC .5.Extracted Ratified Minutes 16 .