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. Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 313
Interactions between traditional herbal medicines & pharmaceutical medicines 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
Physico-chemical Properties
Biomedical Properties
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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, Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 315
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
dru inter
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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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 317
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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 318
Interactions between traditional herbal medicines & pharmaceutical medicines 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
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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 319
Interactions between traditional herbal medicines & pharmaceutical medicines 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%)
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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
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). Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 321
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
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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 322
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
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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 323
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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 324
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
reactions due to herbal medications or related The possible outcomes may be as follows: 1. If the SXT decoction is effective to reduce Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 325
Interactions between traditional herbal medicines & pharmaceutical medicines Figure 2. Study design for drug interaction studies in cancer patients
Run-in phase
n cal measurement
in c mbina
i h placebo ***
tie t No. w
A sessment of
and other
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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 326
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, Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 327
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
Hospital if relevant ________________________________________ Hospital Number ____________ Date of birth (or age)__________ SUSPECTED CHINESE HERBAL MEDICINAL PRODUCTS
Give brand name of formulae or
___/____/__ ___/___/___ ________________ ___/___/___ __/___/____ ________________


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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 328
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 Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 329
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 REFERENCES
(Adinarubella) in treating typhoid. Chinese J Modern Dev Trad Med 2(4): 246. Akerele O. 1993. Nature's medicinal bounty: Don't throw it Mills S. 1996. Herbal medicines: research strategies. In: Fundamentals of Complementary and alternative Atherton DJ, Sheehan MP, Rustin MH, Whittle B and Guy Medicine, Churchill Livingstone, International Edition, MB. 1992. Treatment of atopic eczema with traditional Chinese medicinal plants. Pediatr Dermatol 9 (4): 373- Ou M. 1989. Chinese-English Manual of Commonly Used Prescriptions in Traditional Chinese Medicine. Joint Chan K. 1995. Progress in traditional Chinese medicine. Rao XQ & Yu RC. 1990. Clinical and experimental studies Chan K. 2000. Observations of the use of Chinese herbal on chemotherapy combined with “Sheng Xue Tang" medicinal products and orthodox drugs. In: Chan K & (SXT) recipe for the treatment of late stage gastric Cheung L, Editors. Interactions between Chinese cancer. Beijing J Trad Chinese Med (1): 46-49 Herbal Medicinal Products and Orthodox Drugs, Ruan J & Ye RG. 1994. Lupus nephritis treated with impact Harwood Academic Publishers, The Taylor & Francis therapy of cyclophosphamide and traditional Chinese Group, June, 2000, Chapter 6, pp. 51-56. medicine. Chinese J Integ Trad West Med 14 (5): 276- Chan K. 2003. Some aspects of toxic contaminants in herbal medicines. Chemosphere 52: 1361-1371. Stockley IH. 1996. Dug Interactions: A source book of Chan K. 2005. Chinese medicinal materials and their adverse interactions, their mechanism, clinical interface with Western medical concepts. J importance and management. The Pharmaceutical Chan K, Lo ACT, Yeung JHK, & Woo KS. 1995. The Wan JMF. 2002. The progress of using Chinese herbal effects of Danshen (Salvia miltiorrhiza) on warfarin medicines in cancer research. In: Chan K & Lee H, pharmacodynamics and pharmacokinetics of warfarin Eds. The Way Forward for Chinese Medicine, enantiomers in rats. J Pharm Pharmacol 47: 402-406. Harwood Academic Publishers, The Taylor and Francis Editorial. 1987. An overview on the combined use of Chinese herbs and orthodox drugs. Chinese J Integr Wu YC. 1984. Treatment of acute bacillary dysentery with traditional Chinese medicine and western medicine Gong L-R. 1989a. Interactions of Chinese patent medicine combined. on analysis of 117 cases. Chinese J Integ and orthodox drugs (I). Chinese J Integr Trad West Xu Y-Z. (1987). Reduction of side effects of streptomycin Gong L-R, 1989b. Interactions of Chinese patent medicine by Gan Cao (Radix Glycyrrhizae). Chinese J Modern and orthodox drugs (II). Chinese J Integr Trad West Ye RG. 1993. 134 patients with adult primary nephrotic Leng F-N. 1988. Editor, Fundamental of Chinese Patent syndrome treated with combined traditional Chinese Traditional Chinese Medicinal Products. (I). People’s medicine and Western medicine. Chinese J Integ Trad Leng. F-N. 1991. Editor, Fundamental of Chinese Patent Zhen Z-A. 1995. History of Chinese Medicine, Shanghai Traditional Chinese Medicinal Products. (II) People’s Zhu J-H 1994. The Interaction of Chinese Herbs and Li PL, Jurima-Romert M. 1997. Drug-drug Interactions: orthodox drugs. People’s Health Publisher Ltd. Beijing, Scientific and Regulatory Perspectives, International Lin B. 1990. A discussion on the interactions of Chinese herbs and antibiotics. Shan Dong J Trad Chinese Med Lo ACT, Chan K, Yeung JHK, & Woo KS. 1992. The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats. Eur J Drug Metab Ph 17: 257-262 Lo ACT, Chan K, Yeung JHK, & Woo KS. 1995. Danggui (Angelica sinesis) affects the pharmacodynamics not the pharmacokinetics of warfarin in rabbits. Eur J Drug Metab Ph 20:41-46. Bol. Latinoam. Caribe Plant. Med. Aromaticas Vol. 7 (6) 2008 | 331

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