Derechos de Publicación 2008 Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 7 (6), 312 - 331
Revisión | Review Especial sobre Interacción de Productos Naturales y Fármacos / Special Issue on Natural Products and Drug Interactions An overview on safety issues of interactions between traditional herbal medicines and pharmaceutical medicines
[Una apreciación global sobre la seguridad de las interacciones entre las medicinas herbarias tradicionales y los
Kelvin CHAN School of Applied Sciences, University of Wolverhampton,Wolverhampton WV1 1LY, United Kingdom
Submitted March 17, 2008; Accepted May 20, 2008; Published Online 15 October 2008
Abstract
The increasing popularity world-wide of using herbal medicinal materials (HMM) from ethnic traditional medicine such as the widely used Chinese materia medica (CMM) or other ethnic herbal medicines and related proprietary health products (PHP), functional food and prescription herbal medicines has raised concerns over their concomitant use with pharmaceutical medicines (PHARMED) and the consequential adverse effects. In most cases the alleged causes of adverse effects are linked with herbal substances, although the authoritive information on the interactions between HMM/PHP and PHARMED is not plentiful in the literature. There is an urgent need for such a data base. In the 21st century, the public are more informed, from the Internet, about health and medical products and become more knowledgeable about matters relating to their health conditions and well-being in curing and preventing illnesses. They often self-medicate themselves with various health products as well as those over-the-counter (OTC) PHARMED. Some of theses products may have doubtful quality control and contain harmful additives or unchecked ingredients. The future professionals in health and medical care should be knowledgeable or aware of what their patients have been taking or given. Their combining medications may be involved with possible outcomes of adverse reactions or beneficial effects. In actual practice the patients may receive both treatments intentionally or unintentionally, with or without the awareness of the practitioner. In these situations an available authoritive database for interactions between HMM/PHP or prescribed PHARMED will be extremely useful for consultation when treatment problems appear or during emergency situations. Such a database will be welcomed by both practitioners of herbal medicines and orthodox medicine (OM) practitioners. The author has been involved in various research projects of basic and clinical aspects in mainly Chinese medicines among other herbal and pharmaceutical medicines hence examples will be given largely on those related to these disciplines as illustrations in this overview. It is envisaged that some of the safety issues and all other aspects discussed in the following texts are also relevant to other traditional or ethnic medicines. Keywords: Principles of interactions, Safety issues, Pharmaceutical medicines, Chinese medicinal materials, Traditional herbal medicines, Adverse reactions, Beneficial effects.
El incremento de la popularidad mundial del uso de los materiales medicinales herbarios (HMM), de la medicina étnica tradicional, tales como la ampliamente usada materia médica china (CMM) u otras medicinas étnicas herbarias y productos propios de salud (PHP) relacionados, alimento funcional y la prescripción de las medicinas herbarias, han aumentado las preocupaciones sobre sus usos concomitantes con los fármacos (PHARMED) y los efectos adversos consiguientes. En la mayoría de los casos, las causas alegadas de efectos adversos están vinculadas con sustancias herbarias, aunque la información autorizada sobre las interacciones entre HMM/PHP y PHARMED no es abundante en la literatura. Existe una necesidad urgente por semejante base de datos. En el siglo XXI, el público está más informado, del Internet, sobre la salud y los productos medicinales y se ha vuelto más conocedor sobre las materias que relacionan a sus condiciones de salud y bienestar, curando y previniendo enfermedades. Frecuentemente, ellos se auto-administran con varios productos de salud como también con productos PHARMED over-the-counter (OTC). Algunos de estos productos pueden tener dudoso control de la calidad y contener aditivos dañinos o ingredientes no chequeados. Los futuros profesionales en salud y el cuidado médico deben conocer o estar conscientes de lo que han estado tomando o han dado a sus pacientes. La combinación de sus medicamentos puede estar involucrada con posibles reacciones adversas o efectos beneficiosos. En la práctica real los pacientes pueden recibir ambos tratamientos intencionalmente o involuntariamente, con o sin el conocimiento del practicante. En estas situaciones será sumamente útil para la consulta una base de datos disponible autorizada para analizar las interacciones entre HMM/PHP o PHARMED prescritos cuando aparecen las reacciones al tratamiento o durante las situaciones de emergencia. Semejante base de datos será bienvenida tanto por practicantes de medicinas herbarias como de la medicina ortodoxa. El autor de esta revisión ha estado involucrado en varios proyectos de investigación de aspectos básicos y clínicos en medicinas chinas principalmente, entre otras medicinas herbarias y farmacéuticas. En esta apreciación global se darán amplios ejemplos en aquéllos casos relacionados a estas disciplinas. Se enfatiza que algunos de los problemas de seguridad y todos los otros aspectos discutidos en los textos siguientes también son pertinentes a otras medicinas tradicionales o étnicas.
Palabras clave: Principios de interacciones, Seguridad, Medicamentos, Materiales medicinales chinos, medicinas herbales tradicionales, Reacciones adversas, Efectos beneficiosos.
Interactions between traditional herbal medicines & pharmaceutical medicines
Abbreviation list: ADRAC- Adverse Drug Reactions Advisory Committee
MHRA- Medicine and Healthcare products Registration Agency
ADROIT- Adverse Drug Reactions On-line Information Tracking
MFC- Methotrexate, fluorouracil combinations
MFV- Methotrexate, fluorouracil, vinblastin
INTRODUCTION
Herbs and herbal products, known as botanicals in
1.1. Observation on the simultaneous
some regions of the world such as North America,
consummation of Chinese Materia Medica
play an important role in the healthcare of nearly
(Chinese medicinal materials, CMM) and
80% of the world population particularly in
Pharmaceutical Medicines (PHARMED)
developing countries (Akerele, 1993). For example,
Chinese medicine (CM), one of the world's oldest
Chinese medicinal materials (CMM) and their
continuous surviving traditions (Zhen, 1995), has
manufactured products as well as Ayurvedic
been practiced to maintain good health and treat
medicines have been used for thousands of years
diseases in the Chinese communities and recently by
(Table 1) for prevention and treatment of diseases in
other ethnic groups worldwide (Chan, 2004). CMM
China and in India, respectively, apart from relatively
and other natural substances and products,
recent introduced synthetic pharmaceuticals in
acupuncture and related physical therapies and
orthodox medical (OM) practice in the late 1800s.
special life style are often used together in the
Without any doubts, all medicinal products used in
practice, co-existing with orthodox medicine (OM) in
human and animals should have proven quality,
China and some regions in the Far East (Chan, 2005).
safety and efficacy (QSE). Problems and difficulties
However in the west increasing uses of CM have
arise in the quality assurance of herbal medicinal
created both scepticism and support of CM practice
products because there are so many unidentified
that have been the major debate since the successful
chemical entities in the finished products, and the
randomized clinical trial on the use of 10 CMM
actual bioactive components are seldom known. The
prescription on atopic eczema was published in 1992
physico-chemical properties and mechanisms of
(Atherton et al., 1992). However available in the
actions of herbal products are quite different from
market are CMM products adulterated with
pharmaceutical medicines (Table 2). Most of the
pharmaceutical drugs and wrongly supplied crude
herbal products from practice of traditional medicine
CMM with liver and kidney toxicity. These
are prescribed using a number of herbal mixtures.
unprofessional practices from commercial
Recent advances in analytical chemistry and
organizations do not give CM the right reputation and
bimolecular techniques and related disciplines have
recognition. It is emphasized that government
regulatory agencies should set up harmonized
compositions and bioactivities of these in natural
regulatory control over the import and export of
products research. Thus the safety issues of
natural or herbal products to ensure safety of the
interactions between traditional herbal medicines, or
the newer botanicals, and pharmaceutical medicines can be addressed on according to the following sections in this overview.
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Table 1. Medicinal products from natural sources in various ethnic cultures. Complementary Medicine Natural Sources Recent Turnover Trade
P- Medicinal plants, A- Animal sources, M- Mineral sources (modified from Chan, 2003)
Table 2: Comparisons between properties of Chinese medicinal materials (CMM) and pharmaceutical drugs. Properties Remarks Products Pharmaceutical Physico-chemical Properties Biomedical Properties Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 314
Interactions between traditional herbal medicines & pharmaceutical medicines
Patients in the Far East intentionally or un-
should practitioners from traditional CM and OM be
intentionally may be prescribed CMM and other OTC
working in isolation. Professionals who are
supportive of this concept of integration should also
PHARMED for alleviating their illnesses. In the past
work to find out if there is any benefit at all in
there were practices of incorporating PHARMED
combination treatments. Augmenting OM with
into CMM preparations. The rationale may be that it
acupuncture has been recognized in several areas of
is hoped to reduce side effects of PHARMED, or to
pain relief, drug dependence, etc. in the West.
produce synergistic effects for better treatment
However this overview only concerns with CMM-
outcome. In most cases the pharmacological
PHARMED interactions relating to beneficial
mechanisms of the combinations are not well studied
outcomes or adverse reactions as a consequence of
and exaggerated adverse effects or therapeutic
failures have been observed, although beneficial
In China, increasing attention has turned towards
effects were noted. Patients may also self-medicate
organized scientific research on this aspect of
with CMM tonic preparations, consumed as dietary
interactions with beneficial outcomes. From the diet
soup during convalescence period, while being
and nutrition aspects many Chinese patients in the
treated with PHARMED. It is well documented that
community often self medicate with tonic CMM
when several PHARMED are taken together, drug-
products after serious illnesses or surgical operations
drug interactions with detrimental effects occur (Li &
while they are still on OM medications. They believe
Jurima-Romert, 1997) and the situation becomes
that the herbs will help them to recover rapidly. It is
more complicated when CMM products are taken
normal procedure to carry out diagnosis of the same
simultaneously. Outside the Far East, apart from the
patient using traditional CM procedures and OM
Chinese communities, non-Chinese ethnic patients
modern instruments and techniques in hospital
will probably be exposed to CMM medications
practice in China. Experienced CM and or OM
through increasing popularity. The problems of
practitioners who are knowledgeable of using both
PHARMED-CMM interactions will exist. Therefore
types of medications have prescribed both types for
adverse reactions consequential to CMM products
certain diseases in order to get effective treatments.
may not be as simple as those due allegedly to
The improvement or deterioration of patients’ disease
toxicity of the herbs only (Chan, 2000).
conditions is the measurement of success or failure of treatment. Some of the observations have been
1.2. The Integrative Practice of Traditional
published, mainly in Chinese, in medical journals
Chinese Medicine and Orthodox Medicine in
The integrative practice of traditional Chinese
2. Mechanisms of interactions between herbal
medicine (CM) into orthodox medicine (OM) in
medicines and pharmaceutical medicines
China since the early 1950s has given the opportunity
In general drug interactions (DIs) refer to clinical
to look at the advantages and disadvantages of each
practice and to investigate the benefit from each
pharmacological or therapeutic actions of a drug are
discipline in order to encourage improvement of
altered by the co-administration of other drugs or
healthcare and possibly save treatment costs. China
substances. The consequence can be advantageous if
probably is the only country in the world that has
used properly. But the clinical outcomes can either
developed a healthcare system that incorporates
be an exaggeration of pharmacological or toxic
traditional CM into the healthcare policy for the
effects or a diminished efficacy of drug treatment;
nation. Within the healthcare system the two forms of
leading to therapeutic failure and endanger patients’
medical treatment work along side with each other at
conditions. The relevance of drug interactions
every level of the healthcare structure. In particular,
depends on how clinically significant is the
patients can benefit from preventive medicine,
therapeutic outcomes. Thus we can consider different
reducing side effects from OM or CM medications
categories of drug interactions. Adverse drug
and improved quality of life in terminal cases. To
interactions can be defined as a situation in which
achieve these goals it will take a lot of understanding
one drug interferes with the pharmacokinetics (at
from professionals of both disciplines. No longer
processes involving absorption, distribution,
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Interactions between traditional herbal medicines & pharmaceutical medicines
metabolism and excretion) or pharmacodynamics (at
microcosmic differentiation of disease state,
receptors, enzyme systems or other sites of actions)
quantitative analysis of regional lesions or tissues
of another. The initial drug can modify the effect of
damages, distinction between different disease based
the second drug, and lead to an enhanced effect,
on characteristics of pathogenic factors and pathology
particularly drug toxicity; or a reduced effect,
of lesions. The CM practice on the other hand, deals
particularly lack of efficacy. Thus, drug interactions
with macrocosmic differentiation of syndrome,
may produce enhanced drug effect that is synergistic;
comprehensive qualitative analysis of whole body,
the outcomes of interactions may be beneficial or
distinction between different syndromes based on
harmful. Interactions can be classified on basis of
complex responses to external and internal
their significance as: major when life-threatening or
pathogenic factors. It is logical to combine
permanent damage is involved; moderate if additional
observations from disease differentiation (OM) and
treatment is required; or minor when the therapeutic
syndrome differentiation (CM) of the patient in order
outcome is unnoticeable or not sufficient to affect the
to draw accurate diagnostic conclusion. Treatment
desired therapy goals. Figure 1 (Adopted from Chan
can be derived to target regional lesion or
& Cheung, 2000) illustrates the possible sites of
malfunction of particular receptor or organ (OM) and
imbalance holistic conditions (CM) of the patient. This is one of the principles for integral treatment
2.1. Beneficial interactions between CMM-
based on CM and OM. Modern medical technology
and sophistication will help to make OM differential
The integral treatment of illnesses using
diagnosis while experience and personal approaches
traditional CM and OM medications aims to bring
is needed for accurate CM diagnosis. It is necessary
together the general concepts of syndrome
to relate the relationship of CM principles of Yin and
differentiation of CM with the OM principles of
Yang balance of the body to the OM understanding of
disease differentiation. It is obvious that the two
the inter-play between the body’s nervous-endocrine-
systems vary greatly in approaches of diagnosis and
treatment. For instance, OM concerns with
Figure 1. The fate of a reversely acting drug in the DRUG + MET DRUG IN DOS dru inter Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 316
Interactions between traditional herbal medicines & pharmaceutical medicines
Experience of integrative medical practice in
western medicine combined on analysis of 117 cases
China has observed, through experience of practice
and recorded case studies, beneficial treatment
The 117 patients with acute bacillary dysentery
observation and outcomes with probable explanation
were divided into 3 different treatment groups,
or possible mechanisms of interactions although more
orthodox medication, PHARMED only, sulfa-
experimental research and clinical evidences are
methoxazole (SMZ 40 patients), Chinese Materia
needed to confirm such observations. This is partly
Medica (CMM) prescription 1 (CMM 1, 36 patients),
because the OM gold standard of randomized clinical
and PHARMED plus CMM prescription 2 (SMZ plus
trials is not entirely applicable in the individualized
CMM2, 41 patients). CMM prescription 1 consisted
approaches for treatment in CM practice. The
of 10 CMM herbs: Bai Shao (Radix Paeoniae Alba),
following tentative categories of case studies
Bai Tou Weng (Radix Pulsatillae), Chi Shao (Radix
illustrate synergy effects of treatment consequential
Paeoniae Rubra), Da Fu Pi (Pericarpium Arecae),
to co-administration of OM drugs and CMM
Da Huang (Radix et Rhizoma Rhei), Dang Gui (Radix
medications. These case studies were abstracted from
Angelica Sinenis), Huang Lian (Rhizoma Coptidis),
medical journals published in China and have been
Huang Qin (Radix Scutellariae), Mu Xiang (Radix
translated into English and edited by the authors for
Aucklandiae) and Qin Pi (Cortex Fraxini). CMM
presentation in the text (Chan & Cheung, 2000). The
prescription 2 consisted of 10 CMM herbs: Bai Zhu
information is reproduced here with permission from
(Rhizoma Atractylodis Macrocephalae), Bai Shao
the author for illustration. Yet most of these examples
(Radix Paeoniae Alba), Bing Ling (Semen Arecae),
did not show any of the ‘gold standard of RCT
Chi Shao (Radix Paeoniae Rubra), Dang Gui (Radix
indicated in the practice of orthodox medicine. The
Angelica Sinenis), Fu Ling (Poria), Huang Qin
debating issues will be that these are reported cases
(Radix Scutellariae), Mu Xiang (Radix
as practiced of integrative medical approaches shown
Aucklandiae),Shan Yao (Rhizoma Dioscoreae) and
in China that illustrate the beneficial treatment effects
Sheng Jun (Radix et Rhizoma Rhei). Four herbs were
when CMM and PHARMED are co-administered
combination medication gave the best results than
Category 1: Combining antibiotics with CMM
either of the two groups with single medication
products producing added benefi-
treatment (P< 0.005). Comments from the publication
cial effects
are: the SMZ had strong bacteriostatic action that
Example 1. Trimethoprim (TMP) and Shui Yang
often leads to disproportionate population of
Mei (Adinarubella) in treating typhoid. (Luo, 1982):
intestinal bacteria and dysfunction of the stomach and
A group of 33 patients took part in the studies and
intestine. The CMM medication is not only free of
they were given 30ml of CMM decoction Shui Yang
side effects, it can also increase the body defense
Mei (orally 3 times a day) plus TMP (0.1g, twice
daily) for treating the typhoid. In the control group,
immunological factors, phagocytosis of reticulo-
21 patients were given sulfamethoxazole (SMZ; 1G)
endothelial system, and by activating the kinase
and TMP (0.1g), twice daily for the same infection.
system it increases the amount of bateriophages in
Both groups of patients were all fully recovered with
no recurrence. The curative effects of the two groups
Example 3: Reduction of side effects of
were mostly identical (P>0.05). But the CMM-TMP
Streptomycin by Gan Cao (Radix Glycyrrhiza). (Xu,
group had no noticeable side effects. From laboratory
experimental evidence, 10% Shui Yang Mei aqueous
It is well known that streptomycin can cause
solution showed bacteriostasis to Shigella
damage to the VIIIth cranial nerve and lead to
dysenteriae. This combined CMM-PHARMED
sensorineural deafness. This toxicity of streptomycin
showed synergic effect on Salmonella typhia.
was reduced when it was co-administered with Gan
Example 2: Treatment of acute bacillary
Cao (liquorices root) extract. About 80% of the
dysentery with traditional Chinese medicine and
patients who previously were not able to tolerate the side effects persisted in streptomycin treatment. Gan Cao is a well-known and widely used CMM, often
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Interactions between traditional herbal medicines & pharmaceutical medicines
incorporated in composite herbal mixture in CMM
combination with others for strengthening the Lung
for frequent colds or shortness of breath. It has no demonstrable anti-bacterial effects but it increases the
Category 2: Combating infection with antibiotics
immune system by increasing the number of ‘stem
and immune-strengthening CMM
cell’ in bone marrow and lymph tissues, promoting
products
immune cells from the ‘resting’ state into heightened
In the Chinese integrative medicine approach,
activity and reducing the negative side effects of co-
bacterial infection in the body can be eliminated by
administered steroids on the immune system. Quite a
using PHARMED antibiotics (i.e. the OM region
few of the CMM products in the form of established
treatment approach) while reinforcing the body
proprietary medications or well-tried prescriptions
immuno-function using CMM herbs to strengthen the
have been shown to possess immuno-strenghtening or
body defense system (i.e. traditional CM holistic
modulating properties. In a review on the role of
approach). The body’s immune system recognizes
CMM in chemotherapy of cancer the principles of
and destroys substances foreign to the body,
such integrative approaches was illustrated by Wan in
including bacterial cells, other microbes, and foreign
toxic compounds. The principles of these combinational approaches can be interpreted as
Category 3: Augmenting cardiovascular PHAR-
follows. Cells in the circulatory and the lymphatic
MED treatment with CMM products
systems that recognize and destroy these cells are
Propranolol, a well used PHARMED belonging to
generated in the bone marrow and the lymphatic
the beta-adrenergic blocker group of therapeutics, has
tissue (thymus, lymph nodes, spleen and tonsils),
been co-administered with aqueous extract of Dan
respectively. These ‘stem cells’ when initially
Shen (Radix Salviae Miltiorrhzae) as intravenous
produced are featureless and cannot be distinguished
injection for treating patients suffering acute
as what type of blood cells (erythrocytes or different
myocardial-infarction in Intensive Care Coronary
kinds of white blood cells) they will become. After
Unit in some hospitals in China since the mid 1980s.
their release into the blood stream they are delivered
The combination treatment gives significantly better
to all parts of the body. Some become ‘memory cells’
outcomes than propranolol alone. Dan Shen aqueous
that as the name implies, recognize specific foreign
extracts, among many other pharmacological
cells or chemicals to which they have been exposed,
properties, increase microcirculation, inhibit platelet
and react immediately on the next encountering of
aggregation and have centrally acting anti-anxiety
those compounds. Substances, such as vaccines, that
actions. These may explain the beneficial effects with
effect the ‘memory cells’ stimulate only to one
co-administration of propranolol. Extensive research
disease or antigen. In general, most herbs that contain
works have been carried out over the past 20 years on
so many different chemical compounds, for the
Dan Shen in Shanghai and Hong Kong academic
immune system do not affect ‘memory cells’, but are
research institutes. It is interesting to note that
isolated single chemical entities from Dan Shen roots
immunostimulants. They induce the activities of the
have not produced any useful and marketable
immune system but are not specific to a particular
conventional PHARMED. Apart from injectables
disease or antigen (i.e. the protein against which
other oral preparations of single herb or composite
immune cells act). They increase resistance by
formulae of Dan Shen are available to the public as
mobilising ‘effector cells’ that act against all foreign
preventive remedies against cardiovascular diseases.
particles, rather than one specific type. Thus the
If these products are not used properly, however,
combination of OM antibiotics with CMM products
adverse reactions may result if taken with other
for treating infectious diseases is a logical approach.
PHARMED to produce harmful interactions (See
This may help to reduce bacterial resistance to
Huang Qi (Radix Astragalus), a widely used
CMM often prescribed as an important herbal component in composite prescription formulae,
alone is used as a tonic herb and as medicinal herb in
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Category 4: Augmenting anti-inflammatory action
steroid with a decoction consisting of 10 CMM.
of PHARMED with CMM Products
These were: Dan Shen (Radix Salviae Miltiorrhzae),
Example 1: Lupus nephritis treated with impact
Di Gu Pi (Cortex Lycii Radicis) Gui Ban (Plastrum
therapy of cyclophosphamide and traditional Chinese
Testudinis), Han Lian Cao (Herba Ecliptae) Hong
Hua (Flos Carthami), Nu Zhen Zi (Fructus Ligustri
The seventy-six patients suffering from lupus
Lucidi),Qi Zi (Fructus Lycii), Sheng Di (Radix
nephritis were divided into two treatment groups,
Rehmanneae) and Yi Mu Cao (Herba Leonuri).
PHARMED with cyclophosphamide and steroid (35
The percentage of success from the corticosteroids
treatment and the combined therapy was 56.1% and
decoction of 14 herbs ( 41 patients). The 14 herbs
85.3% respectively and the corresponding
were, Bai Hua She She Cao (Herba Heyotis
percentages for incidence of side effects were 48%
Diffusae), Ban Zhi Lian (Herba Scutellariae
and 14.8%. These observations indicate that
Barbatae), Dan Pi (Cortex Moutan Radicis), Fu Ling
corticosteroid plus CMM decoction of the 10
(Poria), Han Lian Cao (Herba Eclipitae), Ju Hua
components mixture could enhance curative success
(Flos Chrysanthemi), Nui Zhen Zi (Fructus Ligustri
of adult nephritic syndromes with fewer side effects.
Lucidi), Qi Zi (Fructus Lycii), Shan Yao (Rhizoma Dioscororeae), Shan Zhu Yu (Fructus Corni), Shu Di
Category 5: Reducing adverse effects due to
(Radix Rehmanniae Preparata), Wu Gong
PHARMED chemotherapy during
(Scolopendra), Wu Shao She (Zaocys) and Ze Xie treatment of cancers by CMM products
Treatment of cancers (malignant neoplasm or new
therapeutic efficacy was significantly higher in the
growth) using chemotherapeutic agents is often
combination group than the PHARMED medication
started after not so successful of surgical removal, or
in conjunction with, radiation therapy. At this late
cyclophosphamide is itself inactive; after oral
stage patients become physically weak with quite a
administration it is metabolized to active metabolites.
few signs of adverse effects as the treatment used
In OM practice, prednisone (corticosteroid) is often
often affects normal cells. The most severe toxic
used together in order to increase the rate of
effects include bone marrow suppression, and nausea
metabolism of cyclophosphamide; although single
and vomiting apart from impairment of healing,
doses of the steroid will inhibit activation of this
depression of growth, causing sterility and hair loss.
potent immunosuppressant. Cycolphosphamide
Some patients become in tolerable to chemotherapy
causes liver toxicity and long term steroid treatment
and their quality of life is much reduced. Their
also causes systemic side effects. The use of CMM
immune system is highly compromised. The
may help to build up beneficial effects by rectifying
cytotoxic groups for cancer treatment using
the imbalance of the body functions according to
PHARMED of cytotoxic agents, depending on which
traditional CM concepts. Lupus nephritis usually
cancer types and the policy for chemotherapy, often
manifests itself as Liver-Kidney Yin Xu (deficiency)
consists of at least three and more different groups of
with symptoms such as, lassitude of the loin and legs,
anti-neoplasmic agents. They are anti-metabolites
dizziness, tinnitus, dry mouth and throat, deep and
(cytarabine, fluorouracil, methotrexate, and
small pulse, red tongue with a little coating etc. The
mercaptopurine), cytotoxic antibiotics (bleomycin,
14 CMM in the decoction nourish the Liver and
dactinomycin, doxurubicin, epirubicin, and
Kidney, Yin and clear away Heat, according to the
mitomycin), plant derivatives (etoposide, vincristine),
hormones and their antagonists (glucocorticoid,
Example 2: Observation on 134 patients with
oetrogens such as fosfestrol, anti-oestrogen such as
adult primary nephrotic syndrome with combined
tamoxifen, progestrogens such as megestrol, anti-
traditional Chinese medicine and Western medicine
androgen antagonists such as cyproterone and
flutamide, and gonadotrophin-releasing hormone
The 134 patients suffering adult primary nephrotic
such as goserelin, radio-isotopes such as 131I for
syndrome were separated randomly into two groups
thyroid tumours and inhibitors of DNA and RNA
and treated with corticosteroid (66 patients) and
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Chemotherapy treatment of cancers using integral
The clinical observation was complemented with
laboratory experimental studies that indicated the
practiced in some hospitals in China. The concept is
SXT decoction could prolong the life of the S-180
to utilize PHARMED cytotoxic agents to target the
tumour bearing mice undergone chemotherapy.
cancerous cells and CMM medications for restoring imbalances, as diagnosed from clinical picture, due
2.2. Harmful effects of interactions between
either to the neoplasm or chemotherapy. The
CMM-PHARMED
following examples illustrate some of the
Information on harmful interactions between
CMM and PHARMED medications can be obtained
Example: Clinical and experimental studies on
from the literature mainly available in Chinese
chemotherapy combined with Sheng Xue Tang
language. These information were edited and
(SXT) recipe for the treatment of late stage gastric
compiled into Tables reported previously (Chan &
Cheung, 2000). Some clinical observations have been
Eighty-one patients with late-stage gastric cancer
confirmed with experimental investigation. In general
were treated with chemotherapy (MFV, methotrexate,
the mechanisms described for drug-drug interactions
fluorouracil, vinblastin; or MFC, methotrexate,
in for PHARMED are also applicable for the CMM-
fluorouracil combinations). Among them, 63 patients
also took the CMM composite formula, SXT, while
conventional science and medical aspects.
other 18 patients were treated with chemotherapy
Complications arise because of the presence of so
only as control group. The prescription formula
many chemical entities in the single herb or in the
included following eight herbs: Radix Astragalus;
decoction of the composite formulae, and many of
Radix Pseudostellariae; Caulis Spatholobi; Rhizoma
which have not yet be identified. Such observations
Atyractylodis Macrocephalae; Poria; Fructus Lycii;
are also applied to other traditional herbal medicines.
Fructus Ligustri Lucidi and Semen Cuscutae. Clinical
The following categories summarize the likely
observations showed that the CMM prescription
could reduce the side effects caused by chemotherapy
with improved body weight (see following summaries on Tables 3 and 4).
Table 3. A summary of adverse effects during chemotherapy treatment with and without SXT recipe. Chemotherapy plus SXT recipe Chemotherapy only (control) 33 cases (100%) 12 cases (100%) Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 320
Interactions between traditional herbal medicines & pharmaceutical medicines
Table 4. A summary of changes in patients’ body weight (kg) during chemotherapy treatment with and without SXT recipe. Chemotherapy plus SXT recipe Chemotherapy (control) Aurantii), etc. will decrease the antimicrobial
Category 1: Formation of insoluble complexes
activities of the aminoglycoside group of antibiotics.
during absorption phase leading to therapeutic failure
Some CMM medications whether single herbs or
Category 3: Affecting function of PHARMED
composite prescription decoction or proprietary herbal
diuretics and body electrolyte balance
products contain metal ions that may form insoluble
by CMM medications
chelates or complexes with PHARMED Tannic acid
Some PHARMED diuretics such as the potassium-
in some CMM medications can form insoluble
sparing group (amiloride, spironolactone, etc.;
complexes with PHARMED antibiotics and drugs
Stockley, 1996) should not be co-administered with
containing tertiary amine-alkaloids and metal ions.
some CMM medications. These products (Gong,
Alkaloids in CMM medications form precipitates with
1989b; Zhu, 1994) contain potassium ions in various
forms. Hyperkalaemia may result due to accumulation
containing quercetin (phenols with 5-OH and 4-keto
of the ion from the herbal products and retention from
functional groups) can precipitate CMM drugs
the diuretics. A large group of CMM containing
containing aluminium, bismuth, calcium, ferrous, and
potassium was given as examples in the reference
magnesium ions. Gan Cao (Liquorice root, Radix
Glycyrrhizae) interacts with tetracycline group of antibiotics by reduction of their oral absorption. Yin
Category 4: Destroying amylase in some CMM
Chen (Herba Artemisiae Capillaris) forms precipitates
medications by PHARMED anti-
with quinidine and antagonizes chloramphenicol
Amylase contents in some CMM products are
active principles that can be destroyed by PHARMED
Category 2: Affecting transport of drug molecules
such as the antibiotics tertracylines and
in the body by CMM leading to
sulphonamides. Key CMM includes Dan dou Chi
reduced effects
(Semen Soyae Preparatum), Gu Ya (Fructus Oryzae
Some CMM medications have high contents of
Sativae Germinatus), Mai Ya (Fructus Hordei
acids that will alter the physiological pH and thus
Germinatus), Shan Yao (Rhizoma Dioscoreae) etc.
affect the transport mechanisms of PHARMED drug
(Gong, 1989a; Editorial, 1987; Lin, 1990)
molecules leading to reduced actions or physiological precipitation. Similarly some CMM medications
Category 5: Destroying glycosides in some CMM
contain alkali that affect the physiological solubility of
products by acidic PHARMED
the PHARMED drugs thus influencing their excretion
Glycosides in some CMM products may be the
and transport. For examples, the presence of acids in
active ingredients that can be destroyed if acidic
Nu Zhen zi (Fructus Ligustri Lucidi), Shan Zha
PHARMED (Ascorbic acid, nicotinic acid, glutamic
(Fructus Cartaegi), Shan Zhu Yu (Fructus Corni),
acid and drugs containing mineral acid components as
Wu Mei (Fructus Mume), Zhi Qiao (Fructus
salts) are administered concurrently. (Gong, 1989a;b).
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Interactions between traditional herbal medicines & pharmaceutical medicines
Category 6: Releasing toxic cyanide from CMM
interacting drugs. Unfortunately investigations on
medications by PHARMED
interactions between herbal medicines such as CMM
Some CMM herbs, in particular, seeds when co-
administered with PHARMED release hydrocyanic
documentations in literature are not plentiful.
acid that inhibits the respiratory centre. PHARMED
Moreover many drug interactions that have been
such as codeine, morphine, should not be co-
listed in the literature are at times not meaningful nor
administered with CMM such as Bai Guo (Semen
helpful for clinical practice if they are not relevant.
Ginkgo), Ku Xing Ren (Semen Armeniacae) and Tao
This is because some reported interactions are
Ren (Semen Persicae) (Ou 1989; Leng, 1988; 1991).
theoretically possible on the basis of in vitro investigations or animal experimentation that may not
Category 7: Affecting liver metabolizing enzymes
have been studied in patient situation. Some studies
that eliminate PHARMED by CMM
are based on healthy volunteer investigations or at non-therapeutic doses. The following headings
CMM single herb or complex mixture products
describe possible steps one can initiate studies on
may modify the metabolic elimination of PHARMED
leading to reducing activity (enzyme induction) or increasing activity (enzyme inhibition) of
3.1. Criteria for choosing interaction studies of
PHARMED. The pharmacokinetics of warfarin is
clinical relevance
compromised during co-administration with Dan Shen (Radix Salvia Miltiorrhiza) leading to uncontrollable
Initially, the project leaders should ascertain how
steady state of plasma concentration. (Chan et al.,
valid the reported interaction is, and whether it is
1992; 1995) Warfarin is mainly eliminated by the
worthwhile to design a study to verify the importance
liver and has a narrow therapeutic window during
of the reported or suspected interactions.
clinical treatment when chronic anticoagulation
Investigational studies of drug-drug interactions can
administration is needed. If the steady state is affected
be of predictive value if they mimic the clinical
haemorrhagic or clotting episodes will occur. (Lo et
situation and they can be related to drug combinations
al., 1995). The active ingredient of Gan Cao (Radix
and regimen that are practiced in the clinic.
Glycyrrhizae), glycyrrhizin, is an inhibitor of 11 beta-
PHARMED with problematic disposition and
hydroxysteroid dehydrogenase, a major metabolic
pharmacokinetic characteristics and those required for
enzyme of glucocorticoids in the liver. Co-
long-term treatment carry the higher risk of
administration of Gan Cao potentates the action of
occurrence of possible clinically relevant interactions.
Situations when patients self-medicate or are put on multiple drugs regimen also warrant investigations.
3. Approaches on Research into Interactions
The criteria summarized in Table 5 will be helpful to
between herbal medicines and pharmaceutical medicines
Specific studies, based on the relevant criteria
listed in Table 6, can be carried out during the
From the observations listed in the above sections
development of new drugs (or CMM products refer to
the complexity of interactions between herbal
later headings). These may be designed to measure
ingredients and pharmaceutical drugs is indeed
certain biochemical or physiological processes or
enormous. It is crucial to review steps that can be
functions being affected by drug treatment with
planned to investigate such interactions. One
narrow therapeutic ratios. These functions or
appreciates that only the clinically significant
biomarkers consequential to drug or herbal treatment,
interactions are relevant to clinical practice. As a
or a combination of the CMM or PHARMED are
result of the focus on adverse drug interactions over
useful measurements of adverse, beneficial or
the past decades many of the interactions between
synergic effects. Table 6 gives examples of the
drugs of the PHARMED are now predictable and
pharmacological classes of drugs and respective
unwanted reactions using drug combinations can be
avoided by dosage adjustment of one or more of the
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Interactions between traditional herbal medicines & pharmaceutical medicines
Table 5. Criteria considered as potential risks f or occurrence of drug-drug interactions
Drug-drug interactions of 2 or more drugs observed in clinical practice for confirmations
Drugs with steep dose-response curve (a small change in concentration will lead to exaggerated effects)
Drugs with small therapeutic range especially in combination dosage forms
Drugs with problematic disposition or pharmacokinetics
Drugs used for long term treatment having effects on drug accumulation, enzyme induction etc.
Drugs prescribed simultaneously by several physicians intentionally or unintentionally
Drugs showing genetic polymorphism in metabolic elimination (cytochrome P450 CYP2D6, CYP2C19, etc.)
Table 6. Pharmacological classes of drugs with clinical relevant interactions. Pharmacological Class Functions to be monitored Indices/Biomarkers
Inhibition of drug metabolic elimination
Psychotropic agents (particularly lithium, Hypertensive crisis
made to fill the gap of information on the
3.1. Difficulty and barriers towards research in herbal medicine in developed regions
complementary or herbal medicine. In the
In countries where the healthcare system is run by
practice of orthodox medicine, clinical and scientific
research into the efficacy of herbal medicines in
general using conventional methods has met
difficulties (Mills, 1996). Practical obstacles in
2. Herbal medicinal products are complex
pursuing good research for herbal medicines under
mixtures with a vast amount of chemicals
1. To obtain results with sufficient statistical
prescriptions may have different properties
Herbal medicine presently receives little or
from that of the single constituent acting
alone. Acceptable models for investigation
medicine camp are not readily available.
Medicines set up by the National Institute
consider some orthodox models as relevant
of Health in the USA some efforts have be
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Interactions between traditional herbal medicines & pharmaceutical medicines
to assess herbal products that have been
into account and considered the interaction study
design. Consideration should include the traditional
3. The principles and approaches of using
CM information on the CMM medications and their
herbal ingredients and their effects on the
reported conventional pharmacological group
body is not the same as usually understood
functions. Using this approach it is possible to adopt
study design from the drug-drug interaction protocol
only for those needed for patients. It is considered
holistically evoke healing responses in the
unethical to test on healthy volunteers for such study.
body to rebalance body functions rather than to attack symptoms as orthodox
4.1. Design for interaction study between CMM
medications do. Research of these types on
and PHARMED
Using example of Category 5 under Section 2.1,
‘Reducing adverse effects due to PHARMED
Chinese language are plentiful. This gap
chemotherapy during treatment of cancers by CMM
could be reduced in the near future through
products’, it is possible to design a reasonable study.
In the study reported by Rao et al. (1990), the
indications given for significant successful reduction
In his overview on research strategies of herbal
of side effects were the general well being of the
medicines Mills (1996) gave some positive
patients with stomach cancer on combination of
approaches that could help research on herbal
chemotherapy and Sheng Xue Tang, SXT (literally
medicines in the West. However the progress of
means decoction or recipe producing new blood
‘official’ contribution from herbal medicine to the
components). The results as reported could be more
mainstream healthcare in developed regions has been
significant and convincing if other measure outcomes
were explored and included in the trial. This might be
due to the limited design and certain facilities that were not available during that study. It was obvious
4. Proposed designs for study of interactions
that the chemotherapy with MFV (methotrexate,
between CMM and PHARMED
fluorouracil and vinblastine) should not be stopped
Most of the interactions between CMM and
throughout treatment as decided by the oncologist; the
co-administration of SXT would help to alleviate
observations reported from clinical practice. They
syndromes, due to adverse effects of the MFV
come from the integral approach of medical practices
treatment, as diagnosed by the traditional CM
obtain the beneficial effects of combination treatment
and some are adverse effects due to intentional or
If this trial were to be repeated according the
unintentional combination of the two groups of
present suggested design here, it will include several
medications. These observations are published mainly
entry requirements and other outcome measures with
in Chinese language. Information gap exists on herbal
better statistical assessment. The 81 late stage gastric
medicines and their potential for interaction with
cancer patients could be divided into 3 groups of 21
PHARMED medications. Evidently research in these
each for 3 different treatments of MFV chemotherapy,
areas is urgently needed regions where orthodox
MFV chemotherapy plus SXT decoction and MFV
medical practice is the main stream of healthcare
chemotherapy plus placebo decoction respectively.
provider when their patients consume herbal
Details of design consideration are summarized
medications. The most important step is to obtain
reliable sources of case studies. It may be necessary to accept initially the observed effects as suspected
4.1.1. Trial conditions and procedure
interactions and design studies to ascertain the finding
1. Inclusion of a placebo preparation or decoction
by careful follow-up investigations within the patient
should give a better outcome of a controlled trial.
group who needs the combination herb-drug
A decoction similar in color, smell but without the
treatment. All information on the interacting
traditional CM effects could be prepared. The
PHARMED stated in Tables3 and 4 should be taken
successful controlled trial in the atopic eczema
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Interactions between traditional herbal medicines & pharmaceutical medicines
study (Atherton et al., 1992) also included a
placebo to increase the trial’s confidence level of
due to the immuno-protective or -stimulant
2. Entry by randomization of number of patients into
the three treatment groups was a better design.
confidence level of the significance will be
Thus the ‘Chemotherapy plus Sheng Xue Tang’
higher due to the randomization and inclusion
group and the ‘Chemotherapy plus Placebo Tang’
of a placebo. The clinical biochemistry and
could be compared with the Chemotherapy group
function tests and related biomarkers would
3. Pre-chemotherapy profiles of all patients for
clinical biochemistry and hematology and kidney
and liver function should be available and
recorded accordingly together with other
parameters for assessment of well being using
PHARMED cytotoxic drugs could be altered
Quality of Life instruments specifically for cancer
group patients. The well being measurements
should be administered by trained persons based
preparations. This alternation could only be
on properly designed questionnaires. The person
making the assessment should be blinded of both
4. Measurement of adverse effects should also be
4.2. A co-ordinated effort for reporting of
performed with thoroughly designed protocol and
Adverse Drug Reactions (ADRs) involving
recorded without biased remarks or comments.
herbal medicines
Same procedures should be administered for every
Medical practitioners in main stream healthcare
practice in developed countries or regions have
5. Run-in steady state of basic chemotherapy
expressed the concern and fear of herbal
treatment should be achieved by measuring the
medicines and related products causing toxicity
pharmacokinetic parameters of the chemotherapy
and adverse effects. Yet reported cases of toxicity
drugs during the first week before giving the SXT
decoction or Placebo Decoction. Evaluation of
information such as those of the prescribed herbal
pharmacokinetics of the chemotherapy drugs
materials or related products, pre-treatment
clinical profiles of patients’ bio-chemistry,
6. Determination of pharmacodynamics and
hematology, liver and kidney functions and
pharmacokinetics after steady state has attained
PHARMED that were co-administered. This can
should be carried out. Observation of adverse side
only lead to difficulty in drawing clear
effects and improvement or deterioration of blood
conclusions of the significance and relevance of
picture and other related. Indices or other related
the interactions described. Data as mentioned in
biomarkers for cancer progression should be
the Section 4 of the present overview on proposed
design for study of interactions will be needed for consideration. Some other reported cases of toxic
4.1.2. Assessment Outcomes
reactions due to herbal medications or related
The possible outcomes may be as follows:
1. If the SXT decoction is effective to reduce
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Interactions between traditional herbal medicines & pharmaceutical medicines
Figure 2. Study design for drug interaction studies in cancer patients Run-in phase pharmacodynam n cal measurement pharmacokinetics pharmacokinetics pharmacokinetics in c mbina i h placebo *** tie t No. w A sessment of clinical and other measuremen Outcomes assessment
have involved unqualified practitioners or the
quality information to make decision on all
products that were adulterated with PHARMED.
medications regarding restriction in use, reduction in
These can be related to poor documentation of
dose, or special warnings and precautions.
reporting incidents of adverse reactions. Moreover rarely are reported of the beneficial effects resulting
4.2.1. The Yellow Card Scheme
from the intentional co-administration of both CMM
Working with the Medicine and Healthcare
and PHARMED in integrative medical practice.
products Registration Agency (MHRA) the UK
Proper evidence-base investigations are essential for
Committee on Safety of Medicines has established the
further development. Contributions from these
Yellow Card Scheme (Rawlins, 1988, 1988a) for
practices are urgently needed to enlighten the benefit
reporting adverse reactions of medications since 1964.
of complementary medicine towards healthcare world-
The system receives reports of suspected ADRs
directly from doctors, dentists, coroners, pharmacists
In handling adverse reactions of PHARMED, well-
and other health professionals and indirectly through
established reporting schemes have been in operation
pharmaceutical companies. It is the UK Adverse Drug
in some developed regions. The author is familiar with
Reactions Reporting Scheme that these received
schemes operating in the UK and Australia. The
reports are placed on a specialized computer system,
intention is to describe briefly here such that by
Adverse Drug Reactions On-line Information
modifying and adopting these two schemes it is
Tracking (ADROIT), to facilitate rapid processing and
possible to use the principles behind for recording and
analysis. The scheme has been critically important in
reporting adverse reactions involving CMM or other
monitoring drug safety for all PHARMED in normal
herbal medicines with PHARMED interactions. A
clinical practice, increasing knowledge about known
centralized co-ordinating effort will be needed for
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Interactions between traditional herbal medicines & pharmaceutical medicines
adverse reactions, and acting as an early warning
including herbal, traditional or alternative remedies.
system for the identification of previously un-
Regular Australian Adverse drug Reactions Bulletin is
recognized adverse reactions. The organization and
distributed to appropriate healthcare professionals for
operation of the Scheme includes collection of reports
their information free of charge. A modified ‘Blue
of suspected adverse reactions, data processing,
Card’ is proposed to deal with reporting or recording
verification and confirmation of information, and
interactions between CMM products and PHARMED
dispatching of advice etc. The data received from
for practitioners’ self-regulatory practice (Table 8).
reports of suspected ADRs will be analyzed and
Other countries in developed regions may also have
presented and dispatched via the ‘Current Problems in
similar establishments who would deal with ADRs
Pharmacovigilence’ which is distributed to all doctors,
reporting. Whatever systems are available, it is
dentists, coroners and pharmacists periodically
possible to modify them for reporting and recording
ADRs due to interactions between CMM medications
Obviously the accuracy of initial source of
information of the suspected adverse reactions is extremely important. Guidelines on reporting are
5. Establishing a data base for safety issues on
given. Table 7 shows a general format of reporting
interactions between CMM and PHARMED
suspected adverse reactions arisen due to CHM
Most of the CMM used for prevention or treatment
medication-OM drug interaction proposed for action
of diseases according to traditional CM practice are
by the authors (Chan & Cheung, 2000). It is also a
considered safe, even when potent/poisonous herbs
suggestion for traditional CM practitioners and OM
are included. This is because, according to Chinese
practitioners’ Good Clinical Practice to self-regulate
Medicine Theories, when administered as mixtures of
until a similar scheme is accepted by appropriate
CMM, composite formulae (Fu-Fang, in Chinese),
health organizations in regions that such a scheme is
through proper combinations of CMM may interact to
considered for monitoring. It is adopted from the UK
enhance the therapeutic efficacy and to eliminate or
Yellow Card Scheme reporting card issued by the
minimize adverse reactions. It is considered that toxic
Scheme operators. It is understood that the present UK
CMM could be rendered non-toxic or less toxic
Scheme also welcomes inclusion of suspected adverse
through such combinations. Fu-Fang is the basic
reactions due to herbal medications. Table 7 listed
practice in Chinese Medicine prescribing. Yet there is
categories of ‘Adverse Reactions’ considered serious
little published scientific data in the west to
for reporting as specified in the UK Yellow Card
substantiate such observations that have sustained
Scheme. In general, serious reactions include those
through test of time. Nevertheless, poisoning cases do
that are fatal, life-threatening, disabling, incapacitating
occur due, probably, to one of the many reasons such
or that result in or prolong hospitalization.
as: lack of understanding on how to use CMM; improperly processed items; over-dosing; use of fake
The Blue Card System
or substituted CMM; contamination especially by
heavy metals and/or insecticides; poor quality control
depending on convenience and circumstantial
during manufacturing and adulteration with
situations, to adopt the Blue Card System initiated
pharmaceutical drugs; and interactions between CMM
originally by the Adverse Drug Reactions Advisory
and co-administered pharmaceuticals. Hence it is
Committee (ADRAC), a subcommittee of the
important to identify where the toxicity comes from
Australian Drug Evaluation Committee, who
and what aspects of toxicity are measured.
encourages the reporting of all Suspected Adverse
Reactions to drugs or other medical substances,
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Interactions between traditional herbal medicines & pharmaceutical medicines
*Table 7. Form for reporting suspected adverse reactions due to interactions of Chinese herbal medicines and pharmaceutical medicines
information is kept as confidential records
Do not be put off reporting because some details are not known
REPORTER: HEALTH CARE PROFESSIONALS OM PRACTITIONERS/TCM PRACTITIONERS
Hospital if relevant ________________________________________
Hospital Number ____________ Date of birth (or age)__________
SUSPECTED CHINESE HERBAL MEDICINAL PRODUCTS Give brand name of formulae or
___/____/__ ___/___/___ ________________
___/___/___ __/___/____ ________________
ORTHODOX DRUGS TAKEN IN THE LAST 3 MONTHS INCLUDING SELF-MEDICATION Give brand if known. Write None if
no other drugs has been taken ________________________ ___________
___/____/__ ___/___/___ ________________
___/____/__ ___/___/___ ________________
___/____/__ ___/___/___ ________________
___/____/__ ___/___/___ ________________
___/____/__ ___/___/___ ________________
SUSPECTED REACTIONS Is the patient hospitalised Date reaction Date reaction Outcome eg. fatal
___/____/__ ___/___/___ ________________
___/____/__ ___/___/___ ________________
___/____/__ ___/___/___ ________________
___/____/__ ___/___/___ ________________
Relevant additional information including medical history, investigations, known allergies, suspected drug interactions. For congenital abnormalities state all other drugs taken during pregnancy and the LMP. Please attach additional pages if necessary ______________________________________________________________________________________ ______________________________________ If you would like information about other reports associated ______________________________________ with the suspected drug , tick here
Adopted form the Yellow Card Scheme for Reporting ADRs, UK
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Interactions between traditional herbal medicines & pharmaceutical medicines
*Table 8. Form for reporting suspected adverse drug reaction involving interactions of Chinese herbal medicines and pharmaceutical
(Note: Identities of Reporter, Patient and Institution will remain Confidential) All Chinese Herbal Medicinal Products and OM Drugs Daily Dosage Date Stopped Reason for Prior to Reaction and Route
Comments (eg. relevant history, allergies, previous exposure to this drug):
Return Forms(s) To University Department on Professional Association of Traditional Chinese Medicine Address:
Adopted from the Blue Card System of the ADRAC, Australia
potent or poisonous are seldom used singly, and when
5.1. Assessment of Intrinsic Toxicity of CMM
used in clinical settings where the principles of CM
Intrinsic toxicity of properly processed (i.e. Quality
are not understood or not followed, their use can be
Control-checked) potent/poisonous CMM can be
highly dangerous. Experience and incidents of
assessed using various models available. Specific
occurrence can be shared via networking. Existing
potent/poisonous CMM included in well-known
toxicology models can be used to ascertain the toxicity
composite formulae have survived the test of time, but
of the Fu-Fang. For examples, cardiac, liver and
such potent CMM and Fu-Fang containing them,
neurological toxicity can be assessed, using cell
although included in the Chinese Pharmacopoeia, can
culture and in vivo animal models if toxicity is
only be prescribed by qualified traditional CM
practitioners. Individual CMM, which are highly
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Interactions between traditional herbal medicines & pharmaceutical medicines
cytochrome P450 isozymes; interaction with P-
potent/poisonous or non toxic CMM, if needed for
glycoprotein and other efflux mechanisms, plasma
assessment, is far more difficult and may not be
protein binding and clinical pharmacokinetic
relevant to the composite use of CMM. Most of the
interaction trials may be performed. Experimental
authenticated CMM, when used properly in the form
results can produce an indication of inhibition or
of decoction, have stood the test of time for their
induction of various isoforms by CMMs, which can
safety issues as Pharmacopoeia composite formulae.
alter the metabolic properties of drugs, thus resulting
Nevertheless, if toxicity assessment is needed in vivo
in changes in the pharmacological and/or toxicological
animal models can be used. But other forms of
effects of other drugs administered concurrently. To
extraction in proprietary Chinese medicines (PCM) of
establish a battery of such tests and validate their
these CMM may show toxicity that has not been
contribution to the clinical assessment of the potential
tested in human use. The toxicity of these PCM should
problems of individual interactions will be an
be assessed according to those animal toxicity tests
important contribution to healthcare when the two
used for pharmaceuticals. The opportunity of
groups of medications are co-administered.
networking to exchange experience in these issues will be beneficial to acquire the present understanding
5.3. New methodologies and techniques for
and allow future drafting of guidelines for what
quality, safety & efficacy evaluation of CMM
The evaluation of CMM safety is complicated by
multiple factors, such as the geographical origin of
5.2. In vitro and in vivo methods to assess
plant material, different processing techniques,
CMM-PHARMED interactions and clinical
dosage, route of administration and compatibility with
other medicines. This variation in chemical
As mentioned above, one of the major causes of
constitution can make it difficult to elucidate the toxic
toxicity of CMM may come from interactions between
component(s) and to explain all the pharmacological
them and pharmaceutical medicines. Such information
mechanisms of CMM. The advent of system biology
in the English text is not abundant; the situation of
including metabonomics, which provides a new
integrative practice of traditional CM with orthodox
platform for the study of CMM in the post-genomic
medicine has shown both beneficial and adverse
era, and has been successfully applied in many other
effects of CMM when co-administered with
fields such as drug discovery, phytochemistry, and
pharmaceutical medicines. Data collections from
clinical research. Due to the diversity in polarity,
practices within and outside China will be essential to
molecular weight, and concentrations of active
identify such observations. The database will collate
molecules, it is generally accepted that a single
all published reports of experimental, theoretical data
analytical technique cannot provide sufficient
and clinical reports of toxicity and CMM-PHARMED
visualization of the metabolome, and multiple
interactions. This is important as laboratory
technologies are needed for a comprehensive view.
‘predictions’ do not always correlate with significant
NMR, chromatographic and their hyphenated
clinical adverse events, and it is important to validate
techniques are the most popular analytical methods
experimental methods. The lack of reliable data has
used. As with the treatment concept of CMM, the key
led to a situation where theoretical and unproven
point of metabonomics is to emphasize holistic
potential interactions are presented as effects, especially regarding clinical efficacy and contraindications, despite a lack of clinical reports
potential toxicity. Metabonomics can identify the
confirming them. This practice is immensely
principle changes in the chemical components and
damaging to the perception of traditional CM by the
pharmacological activities of CMM under different
orthodox medical and pharmacy professions, and is
conditions. Combined with in vivo and molecular
biology protocols, metabonomics can help to explain
To ascertain the validity and relevance of CMM-
mechanisms and evaluate the safety and efficacy of
PHARMED interactions a series of cell culture and in vivo models can be devised using expertise in China and other regions as appropriate, to test the effect of CMM on the inhibition or induction of a range of
Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 330
Interactions between traditional herbal medicines & pharmaceutical medicines
Luo R-D. 1982. Trimethoprim (TMP) and Shui Yang Mei
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QUESTIONNAIRE DÉMOGRAPHIQUE Date/Expérimentateur__________________________________________ Screening: Informations démographiques générales RAPPELER AU PARTICIPANT LE POTENTIEL DE CONFIDENTIALITÉ Code assigné au participant, si éligible ________________ Avez-vous déjà participé à une étude au Centre d’étude sur le stress humain? Si oui, pouvez-vous vous rap
Human Reproduction Update, Vol.8, No.3 pp. 201±215, 2002Hormone replacement therapy and the prevention ofHelena J.TeedeAddress for correspondence: Monash University Department of Medicine, Vascular Medicine and Sciences Unit, DandenongHospital, David St, Dandenong 3175, Victoria, Australia. E-mail: h.teede@southernhealth.org.auCardiovascular disease (CVD) is the primary killer of both men and