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 Directors Order
MEC
Medicines Evaluation Committee
MHRA
Medicines and Healthcare products Regulatory Agency

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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, Hilton Hotel, Melbourne Airport, Melbourne, from 9.30 a.m. to
3.50 p.m. on Friday 9th June 2006.
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

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PROCEDURAL MATTERS

1.1

Opening of M eeting

The Chair opened the meeting at 9.30 am and welcomed CMEC Members and TGA staff.
1.2

A pologies

The CMEC Secretariat recorded the following apologies:

Professor Bill Webster
Associate Professor Heather Yeatman
1.3

C onflict of I nter est

Members submitted conflict of interest declarations specific to agenda items for this meeting
to the Chair.
1.4

C umulative index of issues consider ed at C M E C meetings

Members noted the revised CMEC index.

CONFIRMATION OF MINUTES OF CMEC 57 (9 JUNE 2006)

Members accepted, without amendment, the minutes of the fifty-seventh meeting of CMEC as
an accurate record of proceedings.
R ecommendation 58.1
C M E C confir ms that the dr aft M inutes of its pr evious meeting (C M E C 57, 9 J une 2006),
ar e a tr ue and accur ate r ecor d of that meeting.

GUIDELINES ON LEVELS AND KINDS OF EVIDENCE TO SUPPORT

CLAIMS FOR THERAPEUTIC GOODS (GUIDELINES)

CMEC did not consider any matters under this agenda item.

JOINT AUSTRALIAN / NEW ZEALAND THERAPEUTIC PRODUCTS

AGENCY MATTERS

4.1

Plant par ts pr oject - H er bal mater ials with potential safety issues

Background
A TGA Officer introduced this item, 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.
CMEC Members were asked to review the regulatory status of a number of herbal species, to
ensure that all plant parts available for selection for a listable herbal species are relevant, and
are those on which a history of safe use of the plant has been based.

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Members noted that for some herbal materials, particularly those commonly used in other
traditional paradigms, additional regulatory controls may need to be considered.
Discussion
Members agreed that the formation of a herbal working party was the most appropriate
strategy to manage this task. Members further agreed that expertise in western herbal
medicine and Ayurvedic herbs would be beneficial in reviewing the nominated herbs.
Members agreed that the OCM should determine meeting dates - on an as needs basis, in
consultation with working group members.
R ecommendation 58.2
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.

4.2

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, and the OCM
Industry Consultation Group (OICG), on a number of previous occasions.
Members were advised of the proposed approach to the standardisation of herbal-derived
ingredients which the OCM understands has been agreed to, at this point in time, based upon
CMEC and OICG recommendations to date.
In considering this paper, the TGA Officer advised Members that, at the May OICG9
meeting, there was considerable discussion, and some disagreement on this matter. This may
have been partly due to the complexity of standardisation as an issue, and the overlap with
several other herbal issues yet to be fully resolved such as naming, quantification,
equivalence, quantified by input, and acceptable ranges for ingredients in medicines.
The Officer noted that recent discussions with industry have identified acceptable ranges and
limits for quantifying standardised ingredients as the main area of contention. It is
anticipated that this matter will be resolved at the next meeting of the OICG.
Discussion
Members generally agreed that the issue of standardisation had been sufficiently considered
by the CMEC on previous occasions. However, analytical precision was raised as a potential
area of concern.
The TGA Officer explained that the proposed approach to standardisation was, in part, to
ensure that quantification of herbal components is consistent industry-wide. The use of
consistent analytical methods will assist consumers to better compare dosages in products.
However, the Officer noted that if the amount of the herbal component in the product varies
significantly (i.e. the analytical range for the component is broad), and the product is
quantified with a 'not less than' value, this could result in a much more variable dose. For
example, if the expected herbal component range is 76-93mg, and the label states that a
product contains 75mg of the component (the not less than value), if a batch came in within

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limits at 93mg, the consumer would be receiving a considerably higher dose than is recorded
on the label. The TGA Officer also noted that the issue of acceptable limits for standardised
ingredients, particularly where due to inherent assay variability, may need to be revisited.
Overall, Members endorsed the proposed approach to the standardisation of herbal
ingredients.
4.3

E quivalence of extr acts: Dr aft guideline

A TGA Officer noted that at CMEC 56 (April 2006), Members considered numerous factors
that could affect the equivalence of herbal extracts, both in terms of composition as well as
quantity of the native extract.
Members noted that different solvents, solvent concentrations and extraction methodology
may result in preparations with different safety and efficacy profiles, and were asked to
consider what variation, if any, should be permitted for extracts of the same herbal material.
Members were requested to consider the draft guideline: Guidance on Equivalence of Herbal
Extracts, which, when finalised, will form an adjunct guideline to the Australian Regulatory
Guidelines for Complementary Medicines (ARGCM).
The Committee endorsed the guideline in its current form.
4.4
I nfor mation sessions: Pr oposed r egulation of homoeopathic and
anthr oposcophic medicines, and essences
A TGA Officer advised the Committee that information sessions have recently been held in
Auckland and Sydney, to explain the proposed approach to the regulation of homoeopathic
and anthroposophic medicines, and essences in the proposed Australia New Zealand joint
regulatory scheme.
Members noted that these sessions were well-received, and attended by a wide range of
stakeholders, including manufacturers, sponsors, practitioners, consumer groups and
educators. These meetings provided an opportunity for individuals and groups to gain a more
comprehensive understanding, not only of the proposed approach to the regulation of these
products, but also of the views held by other stakeholders.
Attendees were given the opportunity to discuss issues of quality standards, including good
manufacturing practice (GMP); permitted ingredients for products containing homoeopathic,
anthroposophic and essence preparations; evidentiary requirements to support indications and
claims, and to raise any other matters of concern.
Members noted that a copy of the meeting presentations is located on the Australia New
Zealand Therapeutic Products Authority (ANZTPA) website at:
http://www.anztpa.org/cm/0607pres-is-hae.htm
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, or references, a number of monographs which pertain to
herbal preparations. These monographs are the default standards for such ingredients when
included in medicines supplied in Australia.
CMEC Members were provided with an attachment, which listed those monographs included
in the current edition of the BP relating to herbal ingredients. This attachment also included a
list of herbal substance (AHS) names that have been approved for use in medicines. Members

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were reminded that the AHS name is a 'complete' name, which links to a pharmacopoeial
monograph, which in turn outlines the permitted species, plant part and preparation.
Members were advised that in the past there was not always a relevant BP monograph with
which to link an AHS name. With the increase in the number of applicable BP monographs,
some interesting overlaps have been created, and these were outlined in the attachment.
Any ingredient that complies with the definition included in a BP monograph is required to
meet the quality standards of that particular monograph. Members were advised that a review
of this overlap is required, to ensure that the linked pharmacopoeial monograph for each AHS
is appropriate.
Members were advised that once reviewed, the list of herbal preparations which are covered
by a BP monograph, together with the associated AHS name, will be brought to the attention
of stakeholders via the TGA website.

ACTION ARISING FROM PREVIOUS MEETINGS: CMEC 57

CMEC considered several matters under this agenda item.

EVALUATION OF NEW SUBSTANCES

6.1

Omega-3-mar ine tr iglycer ides

Background
A TGA Officer introduced the new substance, which is characterised by a monograph in the
British Pharmacopeia (BP). The Officer indicated that this substance is comprised of a
mixture of mono, di and triglycerides and is essentially a reconstituted fish oil, with the
source of the fatty acids originating from the oil from a variety of families of fish.
The standard for omega-3-marine triglycerides specifies an eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) content of not less than 45%, with a total omega-3 content of
not less than 60%.
The Committee was reminded that 'refined' or 'natural' fish oils (Fish oil, Rich in Omega-3
Acids) presented as a 'For information' paper at CMEC 57, has a minimum omega-3 content
of 28%, which includes a minimum EPA and DHA content of 22% (as per the adopted BP
monograph of the same name).
Reconfiguration of the fish oil starting material to create the material known as omega-3marine triglycerides occurs via hydrolysation of the fish oil, from which the fatty acids are
separated out. 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 TGA Officer also noted that earlier this year, 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. The Officer indicated
that there is increasing interest from industry in this growing worldwide market, which has
found that in order for consumers to get the required dose of omega-3 fatty acids, they need to
consume large amounts of fish oil. This has been a driving force for concentrating the
omega-3 fatty acids. In addition, 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.

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A search of the ARTG by the TGA examining the fish oils currently on the market suggests
that, on the basis of the EPA and DHA content, some of the concentrated fish oil products are
already on the market.
The Officer noted that while there was such a vast amount of available literature on fish oils,
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. Thus, despite the extensive global use
of fish oils, few safety studies per se could be identified.
Nonetheless, 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,
this is likely to occur regardless of the source of the oil, and appears related to total dosage of
omega-3 fatty acids.
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, respectively in the briefing paper. 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.
Discussion
Characterisation: Members were asked to consider whether this substance was adequately
characterised. Given the presence of an associated BP monograph, Members were satisfied
that this substance was adequately defined from a compositional point of view. However, it
was noted that sponsors may have difficulties meeting some of these specifications.
Safety: Members considered the critical issue was that of safety and risk of toxicity.
Members noted the increased risk of bleeding and alteration of glycaemic control at high EPA
and DHA doses. Members considered that the increased bleeding was likely related to a
prostaglandin-mediated process. One Member suggested that it probably represented a
balance between platelet aggregation and disaggregation prostaglandin- mediated processes.
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.
Members came to the view that there were no safety concerns with this substance, despite the
limited safety data. One Member also considered the increased bleeding time at high doses
may be related in part to the therapeutic response.
On this basis, one Member considered whether it was worthwhile having a label warning to
advise consumers against concomitantly having a fish rich diet. However, it would be
unlikely that fish oil supplements would be taken if the diet was rich in fish. The Member was
concerned that if this substance was just fish, generally the whole fish would be consumed
whereas there are significant modifications to the oil occurring. In response, 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, by
comparison, are not naturally occurring constituents of human cells.
Members considered this evaluation part of an inevitable process in the emerging role for fish
oils. Overall, they considered fish oil, in the form omega-3-marine triglycerides, a more
favourable option for people taking fish oils compared to that currently available.
Members voted unanimously in favour of option 1, considering omega-3-marine triglycerides
suitable for use as an ingredient in Listed Medicines, noting its defined monograph,
worldwide consumption and absence of remarkable safety concerns as reasons underlying this
decision.

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R ecommendation 58.3
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.

6.2
CMEC considered one matter under this agenda item.

SAFETY OR EFFICACY REVIEWS

7.1

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. The Committee was also being asked, depending on the
outcome of these discussions, to endorse the Draft Guidelines developed by the OCM for
these substances.
A TGA Officer provided an overview of these products, which included their regulatory
history and recent developments surrounding their regulatory status.
Hydroxyanthracene derivatives are present in herbs including Senna, Aloe, Cascara, Frangula,
Rhubarb and Buckthorn. They act as stimulant laxatives and are present in many Listed
products including those indicated for constipation, as well as products to aid slimming.
CMEC and its predecessor committee, the Traditional Medicines Evaluation Committee
(TMEC), 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,
particularly when used other than as laxatives (i.e. slimming products).
Draft Guidelines were prepared but never finalised or incorporated into the TGA legislation,
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.
In December 2005, the TGA requested the Committees comments and endorsement of these
guidelines, but CMEC were concerned about the safety associated with prolonged use and
abuse potential of these 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;

on how these products should be supplied and regulated in the future; and

regarding the adoption or need for amendment of the draft Guidelines developed in 1998.

The TGA commissioned a consultancy to address these issues and to update an earlier 1998
detailed review of chemistry, pharmacology and pharmacokinetics.

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This review found that there was very little information available regarding the acute or
subacute toxicity of hydroxyanthracene derivatives.
The overall genotoxicity of herbal preparations containing hydroxyanthracene derivatives
appears complex, with the preparations sometimes demonstrating greater genotoxicity than
the purified chemicals, and sometimes demonstrating an apparent protective effect against
genotoxicity.
Animal studies have not shown an increase in carcinogenicity after Senna administration, but
danthron (1,8-hydroxyanthraquinone) and l-hydroxyanthraquinone have been shown to be
carcinogenic in animals. However, these substances are no longer present in any of the
hydroxyanthracene products sold in Australia. Standard animal carcinogenicity studies have
not been conducted on other anthranoid laxatives, and tumour promotion studies have
demonstrated conflicting results.
There was very little evidence on the effects of anthranoid laxatives on fertility, pregnancy
and lactation, however, there does not seem to be any evidence to suggest specific concerns.
The clinical data available since 1998 has not revealed any previously unidentified adverse
events associated with the acute or chronic use of hydroxyanthracene derivatives. In addition,
the data have not confirmed the suggested association between hydroxyanthracene laxatives
and cathartic colon, habituation/tolerance or colorectal carcinoma. However, 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,
cathartic colon, or habituation/tolerance, the overall body of data published to date does not
conclusively confirm or refute the associations.
There are currently over 400 products listed on the ARTG for oral use that contain one or
more of the anthranoid-containing herbs, which must comply with the ELF rules reflected in
the draft Guidelines currently awaiting CMEC endorsement. Herbal preparations containing
hydroxyanthracene derivatives are contained in laxative preparations as well as diet aids and
more general herbal supplements.
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, much the same as the ELF and the draft Guidelines require.
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; or

to recommend tighter controls for these substances to the TGA; and

to consider whether they wished to adopt the draft Guidelines for incorporation into the
Australian Regulatory Guidelines for Complementary Medicines (ARGCM).

Discussion
Study quality - confounding factors and evaluation outcomes: Members noted that their
attention was focussed on the studies performed since 1998, with particular interest in the
relationship between hydroxyanthracenes and colorectal cancer. They considered that the
various sorts of studies, such as case controls, cohort analyses etc, gave a range of different
answers and that there was not a clear case for a causal relationship, even though there was
some suggestion of increased colorectal cancer risk with hydroxyanthracene derivatives.

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Members acknowledged that there were not just problems with the different types of studies
performed but, more importantly, the substance actually being examined. Some studies
examined the effects of laxatives overall (were not restricted to just hydroxyanthracenes or
stimulant laxatives), while some looked at constipation and laxatives. The biggest problem
identified in these studies was distinguishing causes of the constipation from the effects of the
medicines used. It was noted that laxatives are a very large group of substances, and if the
studies were not restricted to hydroxyanthracenes, it was very difficult to claim that
hydroxyanthracenes are the cause of any identified problems. The studies had not adequately
examined the effects of hydroxyanthracenes and had often failed to adequately account for
confounding factors.
Overall, there was insufficient data for a consistent picture to emerge from which a clear
recommendation for regulatory change could be made. 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.
Members further noted considerable differences in the quality of the studies performed, in
addition to the confounding factors inherent in these studies.
Label warnings - 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, and who had not realised that there may be consequences
associated with long-term use. The Member indicated that they were inclined to support use
of a warning statement about the long-term use of hydroxyanthracenes, as they would with
any stimulant laxative.
A TGA Officer noted that while available data suggests these substances are safe, the absence
of long-term safety data suggests erring on the side of caution, and that if these substances are
going to be used, they should only be used short-term.
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, as
this can lead to habituation and increased hypoactivity of the intestines.") and the EMEA
("For short term use in cases of occasional constipation").
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. 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".
A Member queried whether there were currently any label warnings for these substances. A
TGA Officer confirmed there were but that they did not contain advice about duration of use.
The Officer referred Members to page 59 of the evaluation report, which lists the current label
warnings applicable in ELF for anthranoid laxatives.
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. 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, may be alternative to taking the preparation.

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10

Label warnings - 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.
Members were in favour of limiting the treatment duration in some way and several Members
considered 2 weeks a reasonable maximum duration. The Committee considered the key
issue in deciding this was whether there was sufficient scientific evidence to support any
recommended duration of use.
One Member suggested use of an alternative statement such as "For intermittent use only" or
"Not for long-term use".
Label warnings - focus groups: Two Members indicated that they would like to see the
formation of focus groups to test the consumer understanding of warning statements, such as
"Prolonged use may cause serious bowel problems". They considered that until the
Committee is able to get some idea of what consumers understand of these statements, they
cannot really know whether they should be changed or not. 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.
Alignment with New Zealand: A Member queried how these products were aligned with
New Zealand. A TGA Officer indicated that, while single chemical entity type stimulant
laxatives are sold only in pharmacies in New Zealand, herbal-type products such as those
containing anthranoid compounds are sold as dietary supplements and are currently
unregulated.
Overall, the Committee felt that there was fairly compelling evidence for not changing the
way hydroxyanthracene derivatives are currently regulated. 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. While the Committee favoured limiting the
maximum treatment duration to avoid prolonged use, in much the same way other European
agencies had done, they did not feel justified in setting a figure without supporting scientific
data.
The majority of Members favoured recommending that hydroxyanthracene derivatives
continue to be permitted for use in Listed medicines, without any new regulatory or label
warning changes. Members also endorsed adoption of the draft guidelines.
CMEC, having considered a safety review of ingredients permitted in Listed medicines that
contain hydroxyanthracene derivatives, made the following recommendations to the TGA:
R ecommendation 58.5.1
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, including the cur r ent labelling
r equir ements, 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)

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11

 Do not use when abdominal pain, nausea or vomiting ar e pr esent, or if you develop
diar r hoea. I f you ar e pr egnant or br east feeding, seek health pr actitioner advice befor e
taking this pr oduct. (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, nausea or vomiting ar e pr esent, or if you develop
diar r hoea. I f you ar e pr egnant or br east feeding, seek health pr actitioner advice befor e
taking this pr oduct. (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)].
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.

R ecommendation 58.5.2
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.

REGISTRATION APPLICATIONS

CMEC did not consider any matters under this agenda item.

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12

VARIATION TO A REGISTERED PRODUCT

CMEC did not consider any matters under this agenda item.

10

MATTERS REFERRED FROM WITHIN TGA

10.1

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.

Members noted the adverse drug reaction reports involving complementary medicines from
the 293rd meeting of ADRAC.
Complementary medicine issues
The Member outlined complementary medicines issues of interest, which were limited to two
published papers, one a single case report of warfarin interactions with Matricaria
chamomilla, which was briefly discussed, and the other, a vitamin E paper, which was noted.
Case reports
Members also discussed current case reports and updates on previous case reports in detail.
Members also noted the most recent ADRAC bulletin.

10.2
CMEC considered one matter under this agenda item.

10.3
CMEC considered one matter under this agenda item.

11

FOR INFORMATION

11.1

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.
Members were advised that after receiving seven suspected hepatic adverse reaction reports
associated with Polygonum multiflorum, the Medicines and Healthcare products Regulatory
Agency (MHRA), the TGA counterpart in the UK, posted a safety alert on its website.
Details on the use of the herb were provided in the papers given to Members, with a welldocumented use in traditional Chinese medicine as a liver and kidney tonic.
The Officer noted that there are 79 products containing P. multiflorum on the ARTG with
seven products containing P. multiflorum as the sole active.
The ADRU has received only one adverse reaction relating to P. multiflorum in a 46 year-old
female and the symptoms were suggestive of acute hepatitis.

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13

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.
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.
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.
Another Member queried whether any other Members had prescribed this substance. In
response, 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. They also commented on the
relatively few cases of reported ADRs relative to its high usage.
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, r oot)
11.2

A TGA Officer reminded Members that both the CMEC and ADRAC, after reviewing the
safety of black cohosh, recommended that a warning statement be included in product
labelling advising patients of the risk of liver toxicity.
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. As of February this year, all new black cohosh products will be required to
have the warning statement with a 12 month compliance period given to all other products.
By early 2007, all black cohosh products should have this warning.

12

SPONSOR REPRESENTATIONS TO CMEC

CMEC did not consider any matters under this agenda item.

13

OTHER BUSINESS

CMEC did not consider any matters under this agenda item.

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 58.1
CMEC confirms that the draft Minutes of its previous meeting (CMEC 57, 9 June 2006), are a
true and accurate record of that meeting.
I tem 4.1

Plant par t pr oject - H er bal mater ials with potential safety issues

Recommendation 58.2

CMEC - Extracted Ratified Minutes

14

CMEC recommends that a working group be established to review the safety of certain herbal
materials for continued use in Listed medicines.
I tem 6.1

E valuation of New Substances - O mega-3-mar ine tr iglycer ides

Recommendation 58.3
CMEC recommends to the TGA that omega-3-marine triglycerides (British Pharmacopoeia)
is suitable for use as an ingredient in oral Listed medicines.
I tem 7.1

Safety or E fficacy R eviews - H ydr oxyanthr acene der ivatives

CMEC, having considered a safety review of ingredients permitted in Listed medicines that
contain hydroxyanthracene derivatives, makes the following recommendations to the TGA:
Recommendation 58.5.1
That existing regulatory arrangements for ingredients used in Listed medicines that contain
hydroxyanthracene derivatives are appropriate, including the current labelling requirements,
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, nausea or vomiting are present, or if you develop
diarrhoea. If you are pregnant or breast feeding, 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, nausea or vomiting are present, or if you develop
diarrhoea. If you are pregnant or breast feeding, seek health practitioner advice before taking
this product. (or words to that effect)
This product may have a laxative effect
This product contains [name of herb(s) or chemical component(s)].
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)

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15

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.
Recommendation 58.5.2
That The Guidelines for Oral Products Containing Hydroxyanthracene Derivatives be
incorporated into the Australian Regulatory Guidelines for Complementary Medicines
(ARGCM) as an adjunct guideline.

The Chair closed the meeting at 3:50 pm.

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16