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AUTHOR QUERIES
DATE 10/15/2007
JOB NAME FTD
ARTICLE FTD200373
QUERIES FOR AUTHORS Skalli et al

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AU1) The citation of reference 45 is missing. Please insert it among the citations at the end of this or the next sentence (for
correct sequential order).
AU2) Please provide highest degree for authors Abdelhamid Zaid and Rachida Soulaymani.
REVIEW ARTICLE

Drug Interactions With Herbal Medicines


AU2 Souad Skalli, PhD,* Abdelhamid Zaid, and Rachida Soulaymani*

As with all medicines, however, HM have been shown to have


Abstract: The use of herbal medicines (HM) is on the rise among adverse effects, which are related to a variety of causes,
the global population. Although the safety profile of many herbal including adulteration, mistaken use of the wrong species or
medicines is promising, accumulated data show evidence of misidentification, incorrect dosing, errors in use, contamina-
significant interactions with medications, which can place individual tion (toxic metal, microbes, microbial toxins, environmental
patients at great risk. A range of electronic databases have been pollutants), and toxic constituents (for example, aristolochic
reviewed for articles published in this field: Medline, Allied and acids, nephrotoxins found in Aristolochia species). HM affect
Complementary Medicine Database, HealthSTAR, AMBASE, pharmacokinetic and pharmacodynamic properties of conven-
CINHAL, Cochrane Library, as well as Internet documents and tional drugs and thus cause herbdrug interactions.6 Unfor-
manually searched references in medical journals. In this review, we tunately, clinicians and consumers do not always have
examined the literature from 1966 to 2006 and focused on the information that permits robust inferences about interactions
importance of the risk of drug interactions and potential side effects between HM and prescribed drugs.
when HM are involved. We discuss these in light of the documented HM chemical constituents responsible for pharmaco-
findings. A review of the problematic issues is given and logical activity are many and complex, and the majority of
recommendations are made in order to encourage the setting up of them have not been identified. Distribution of constituents is
clinical trials on HM and herbdrug interactions. not uniform throughout a plant. So, depending on the plant
Key Words: herbal medicines, phytotherapy, adverse effects, herb part used medicinally, chemical constituents could vary both
drug interactions qualitatively and quantitatively. For the same plant part, con-
stituents vary in relation to other factors such as intraspecies
(Ther Drug Monit 2007;29:000000) and interspecies variation in components, climate, harvesting,
drying, storage and transport conditions, preparation method
and method of extraction. On the other hand, HM are usually
INTRODUCTION used as mixtures of two or more plants with different herbal
ingredients specific to each one. In addition to the chem-
Although there are few reliable estimates of the
ical complexity of HM, many patients take these natural
prevalence in use of herbal medicines (HM),1 the market for
products concomitantly with drugs prescribed by their
HM continues to expand rapidly and has grown into a
physicians.
multibillion-dollar industry across the world.2 The influence of
For these reasons, there is a major difficulty in deter-
religious, sociocultural, and socioeconomic issues, traditional
mining the clinical pharmacokinetic and pharmacodynamic
practices, and belief in the use of HM is evident, particularly in
effects when HM are implicated. There is no doubt that there is
Chinese, Indian, and African societies. Documented use of
potential for HM to interact adversely with prescription
HM in Western societies is also high.3,4 Among consumers,
medicines, with danger of injury and even death. There are no
there is widespread belief that remedies of natural origin are
government standards for the quality of HM in most countries,
safe. Worldwide, most HM can be obtained without a pre-
and the main problem is that little is known about them sci-
scription from various sources. The majority of HM are
entifically. Furthermore, HM are not tested with the scien-
harmless in small doses5 (derived chemicals of many plants are
the basis of conventional drug therapies: eg, morphine/ tific rigor required of conventional drugs. The absence of a
Papaver somniferum L.; aspirin/Salix sp.; digoxin/Digitalis). regulatory framework presents the major problem in pharma-
covigilance for HM.
This article highlights the evidence on herbdrug inter-
Received for publication April 11, 2007; accepted September 20, 2007. actions from a systematic literature search using electronic
From the *Moroccan Pharmacovigilance Centre, Rabat; and Natural databases and manual searches from 1966 to 2006. A further
Resources Laboratory, Laboratoire des Ressources Naturelles, Faculte goal is to discuss the particular challenges in this field and to
des sciences et techniques, Errachidia, Morocco. make recommendations to encourage the necessary clinical
Author contributions: Review of concept and design: Souad Skalli, Rachida
Soulaymani; acquisition, analysis, and interpretation of data and drafting trials on HM and herbdrug interactions.
of the manuscript: Souad Skalli; critical revision of the manuscript for For the purpose of this article, the term HM means
intellectual content: Souad Skalli, Abdelhamid Zaid, Rachida Soulaymani; unconventional or alternative therapies and includes herbs,
administrative and technical support: Souad Skalli, Rachida Soulaymani. herbal materials, herbal preparations supplied by herbalists,
Correspondence: Souad Skalli, PhD, Moroccan Pharmacovigilance Centre, Rue
Lamfedel Cherkaoui Rabat-Instituts-Madinate Al Irfane, BP: 6671, Rabat,
and finished or manufactured herbal products found in phar-
Morocco (e-mail: skalli_s@hotmail.com and skallisouadcap@yahoo.fr). maceutical dosage forms (tablets, capsules), as defined by the
Copyright 2007 by Lippincott Williams & Wilkins World Health Organization.7

Ther Drug Monit  Volume 29, Number 6, December 2007 1


Skalli et al Ther Drug Monit  Volume 29, Number 6, December 2007

MATERIALS AND METHODS In general, interactions between herbal medicines and


The search for literature data involved a variety of elec- other medicines are associated more with specific categories of
tronic databases: Medline via PubMed, Allied and Com- HM than others, the quality of the HM, the drug class, the
plementary Medicine Database, HealthSTAR, AMBASE, pathology and the patient population.1720 Many herbdrug
CINHAL, Cochrane Library, Internet documents, and man- interaction case reports can be found in the literature.21 For
ually searched references (WHO documents and books example: St. Johns wort (Hypericum perforatum L., Hyper-
available in Moroccan Pharmacovigilance Centre). The review icaceae) with its main constituents of hypericin, hyperforin,
used the search terms herbal medicines, phytotherapy, herb and flavonoids, is one of the most commonly used HM for the
drug and/or herbherb interactions, adverse effects, herbal treatment of mild to moderate depression in Western countries.
medicines and prescribed drugs, self-medication, herbal It may have an important influence on the effectiveness, safety,
medicines and pregnancy period, and pharmacokinetic and and outcome of a range of drug therapies. This is the case in
pharmacodynamic drug interactions. They were searched in relation to serotonin reuptake inhibitors and warfarin.22,23 In
sources from 1966 to 2006. This involved all articles written the latter case, St. Johns wort decreases the anticoagulant
with a focus on the risk of herbdrug interactions and potential effect when taken with warfarin. The possible mechanism is
side effects with herbal medicines, regardless of whether they hepatic enzyme induction, and there is evidence to suggest
were based on case reports, clinical trials, or other types of this. Warfarin is metabolized by CYP 1A2 in the liver, which is
investigation in humans. There was no language restriction for induced by St. Johns wort24; St. Johns wort and induction of
literature searches. In vitro experiments were excluded. All the human cytochrome P450 enzymes CYP 3A4, CYP2C9,
data were extracted, fully read, and validated by the first author. and CYP1A2.2529 St. Johns wort and cyclosporine coadmin-
One-hundred thirty articles were identified; 103 of them were istration after organ transplantation may result in cyclospor-
retained, of which 62% concerned full text and 38% were ine therapeutic failure in transplant graft rejection,28,30 and
abstract data. This article was written by the first author and St. Johns wort can increase the expression of P-glycoprotein,
validated by the second and third authors (see footnote to with potential drug interactions.3133 P-glycoprotein is vul-
title page). nerable to inhibition, activation, or induction by certain
HM.20,34 Several herbs containing curcumin, piperine, and
catechins have an effect on P-glycoprotein-mediated drug
transport.32 Other examples of potential interactions include
RESULTS AND DISCUSSION those with Panax ginseng species (Araliaceae) and plant
Because HM use has grown significantly, it is important flavonoids. In the case of ginseng, it appears to decrease the
to investigate the potential impact of herbdrug interactions on anticoagulant effect of warfarin, resulting in thrombotic
patient safety and to contribute to public and scientific debate complications,23,24,3538 but the mechanism is not reported in
on this matter. The potential risks resulting from such inter- the literature. Matricaria chamomilla (Asteraceae) appears
actions have received attention in several reviews and are to have the same interaction as ginseng with warfarin,
subject to much current interest,811 but updated information with respect to the coumarin constituent of this plant.37,39
in the absence of rigorous studies to assess the clinical Interaction between ginseng and phenelzine or alcohol is
significance of herbdrug interactions is still needed to guide also reported.35 In patients treated with phenelzine, ginseng
practitioners involved in patient care. may cause headache, trembling, and manic behavior.40 Plant
Herbal medicines are used to treat many different flavonoids, including isoflavones, are natural components of
ailments, from common to serious and from acute to chronic, many plant phenolics and drug-metabolizing enzymes.41
such as diabetes, hypertension, rheumatism, cancer, asthma Despite their common use, it is not widely recognized
and AIDS. Herbdrug interactions may occur in many that HM can alter the efficacy of coadministered prescription
situations, even when herbal medicines are used for weight- drugs. Table 1 summarizes more examples of common herb T1
reduction, performance and energy enhancement, or body- drug interactions.
building. An example is seen with the alkaloids obtained from The evidence from the literature that HM have phar-
species of Ephedra (Ephedraceae), administered as herbal macological effects and may lead to adverse interactions when
medicines or as products containing synthetically prepared coadministered with prescription medicines has grown.4244 AU1
ephedrine and pseudoephedrine. The alkaloids, via catechol- However, there is not enough information or adequate analysis
amines, can cause adverse cardiovascular events associated to estimate the magnitude of the problem.46,47 Pharmacoki-
with arrhythmias, palpitations, tachycardia, myocardial infarc- netic and pharmacodynamic mechanisms account for herb
tion, and death.12,13 Ephedrine raises blood pressure and drug interactions. HM may affect absorption, metabolism,
induces peripheral vasoconstriction. Consumption of caffeine distribution, and excretion mechanisms. A pharmacokinetic
in Coffea arabica L. (Rubiaceae) or present in the same HM or interaction occurs in general when drugs (drugdrug; herbal
in drugs, and in association with ephedrine, increases the drug; and herbalherbal) are coadministered, and one drug
cardiovascular risk.14,15 The danger of using ephedrine- affects the metabolism of the other drug by inhibition or
containing products is higher in patients who are sensitive induction of the specific CYP enzymes involved in its
to the effects of sympathomimetic agents (ie, patients with metabolism.48,49 When HM are coadministered with prescrip-
hypertension, hyperthyroidism, diabetes mellitus, psychiatric tion drugs, there may be induction or inhibition of drug-
conditions, glaucoma, prostate enlargement, seizure disorders, metabolizing enzymes. Altered drug protein binding and
and cardiovascular disease).16 altered drug excretion may also happen, although the degree of

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Ther Drug Monit  Volume 29, Number 6, December 2007 Drug Interactions With Herbal Medicines

TABLE 1. The Most Common Herbal Medicines Reported in HerbDrug Interactions


Medical Plant Vernacular Name Drugs HerbDrug Interactions References
Hypericum perforatum L. St. Johns wort Cyclosporine, Midazolam, Decreases blood 22, 23,
Tacrolimus, Amitriptyline, concentrations 25, 28, 30
Digoxin, Indinavir, Warfarin, of these drugs
Phenprocoumon, Theophylline,
Irinotecan, Alprazolam,
Dextromethorphan,
Simvastatin
Oral contraceptives (ethinyl Breakthrough bleeding and 25
estradiol/desogestrel) unplanned pregnancies
Sertraline, paroxetine, and Serotonin syndrome 25, 30
nefazodone
Antidepressants or Gastrointestinal disorder, allergic 30
serotonergic drugs reactions, fatigue, dizziness,
confusion, dry mouth,
photosensitivity
Allium sativum L. Garlic Saquinavir Decreases plasma concentration 30
of saquinavir
Warfarin sodium Alters bleeding time 30
Paracetamol Pharmacokinetic variables of 25
paracetamol changes
Chlorpropamide Hypoglycemia 25
Panax ginseng Ginseng Phenelzine sulfate Induction of mania and blood 25, 30,
concentration reduction of 35, 40,
alcohol (ethanol) and warfarin; 101
headache; trembling
Estrogens or Corticosteroids Additive effects
Salvia miltiorrhiza (Lamiaceae) Danshen Warfarin Enhances anticoagulation and 30
bleeding
Ginkgo biloba L. Ginkgo Warfarin, aspirin, ticlopidine, Bleeding 38
clopidogrel, dipyridamole
Thiazide diuretic Raises blood pressure 30
Trazodone Coma 30
Levodopa Increases off periods in 25
Parkinson patients
Piper methysticum Forst.f Kava Alprazolam Semicomatose state or coma 30, 101
Cimetidine and terazosin Lethargy and disorientation 30
Benzodiazepines Coma 102
Silybum marianum (L.) Gaertner Milk thistle Indinavir Decreases trough concentrations 30
(Asteraceae)
Glycyrrhiza glabra L. (Fabaceae) Licorice Spironolactone Pharmacological effect offset 101
Echinaceapurpurea; Echinacea; kava; Anticancer drugs Pharmacokinetic interactions 82, 83
Pipermethysticum Forst. f.; ginkgo; ginseng; garlic;
Panaxginseng; Alliumsativum St. Johns wort
L.; Hypericumperforatum L.
Echinaceapurpurea (Asteraceae) Echinacea Anabolic steroids, amiodarone, Hepatotoxicity 101
methotrexate, and ketoconazole
Tanacetumparthenium (L.) Feverfew; garlic; Warfarin sodium Alteration of bleeding time 24, 28, 3537
Sch.Bip. (Asteraceae); ginkgo; ginger;
Alliumsativum L.; ginseng
Ginkgobiloba L.;
ZingiberofficinaleRoscoe;
Panaxginseng
Valerianaofficinalis L. Valerian Barbiturates Excessive sedation 101
Central nervous system Increased drugs effect 101
depressants
Ephedrasinica Stapf. Ma Huang Caffeine, decongestants, Hypertension, insomnia, 12, 14
and stimulants arrhythmia, nervousness,
tremor, headache, seizure,
cerebrovascular event,
myocardial infarction

(continued on next page)

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Skalli et al Ther Drug Monit  Volume 29, Number 6, December 2007

TABLE 1. (continued ) The Most Common Herbal Medicines Reported in HerbDrug Interactions
Medical Plant Vernacular Name Drugs HerbDrug Interactions References
Momordicacharantia L. and Karela or bitter Diabetes mellitus drugs Blood glucose level effect 23, 101
Panaxginseng melon and ginseng
Lycium barbarum L. Lycium, mango Warfarin Anticoagulant effect 24, 103
(Solanaceae), Mangifera indica and papaya increased
L. (Anacardiaceae) and
Caricapapaya L. (Caricaceae)
Trigonellafoenum-graecum L. Fenugreek Glipizide, insulin and Excessive decrease 6062
other drugs that may lower of blood sugar levels
blood sugar levels
Heparin, ticlopidine and Bleeding 67
warfarin
Cyamopsistetragonoloba (L.) Gum guar and Digoxin Plasma digoxin 24
Taub. (Fabaceae) and wheat bran concentration decreased
Triticum spp. (Poaceae)
Boragoofficinalis L. and Borage and evening Anticonvulsants Seizure threshold lower 101
Oenotherabiennis L. primrose oil
(Onagraceae)

susceptibility varies from individual to individual. Drug during gestation or breast-feeding less dangerous than
transporters and metabolizing enzymes are the targets for drugs.6466 Few studies have assessed the use of HM in pre-
herbdrug interaction. Therefore, mechanism-based inhibition gnancy and the factors related to this use. Herbs are taken for
of cytochromes may provide an explanation for some reported venous insufficiency, lactation, gastroesophageal reflux, con-
herbdrug interactions. The best example is herbal interactions stipation, depression, and cutaneous problems and as caffeine
involving cytochrome P450 enzymes.5052 This large family substitutes. Also, HM may be taken for more serious disorders,
of enzymes has been shown to be involved in interactions particularly during the first trimester of pregnancy. Unfor-
between drugs and herbs. Pharmacokinetic interactions often tunately, women ignore that this is the most sensitive period for
occur as a result of changes in activity of drug-metabolizing serious adverse reactions and events.
and transporting proteins: cytochrome P450 isoenzymes In patients who are undergoing anticoagulant pharma-
and P-glycoprotein.53 Herbal medicines, when coadministered cotherapy, HM may interact with cardiovascular drugs.21
with prescription medicines, either induce or inhibit CYP Warfarin is the most common drug involved. Herbs such as
enzymes.54,55 This is exemplified by aristolochic acids con- fenugreek and Ferula communis L. can increase the risk of
tained in Aristolochia species plants undergoing reduction of bleeding (resulting in over-anticoagulation) when combined
the nitro group by hepatic cytochrome P450.56 Use of HM and with warfarin, heparin, and other anticoagulants, due to the
a prescription drug has the potential to decrease or increase the presence of coumarins.67 A case involving giant fennel has
effect of the drug.57 Eleutherococcus senticosus Rupt. & been reported to the Moroccan Pharmacovigilance Centre.
Maxim (Araliaceae), for example, increased the serum Ginkgo biloba L. has been reported to cause spontaneous
concentration of digoxin.58 However, pharmacological and bleeding, and it may interact also with anticoagulants and
clinical data are lacking on the majority of herbal products.59 antiplatelet agents.16 The risk appears to be higher among
Interactions may occur between different HM them- patients on chronic anticoagulation therapy.
selves. Many examples have been reported. One of these Another circumstance is when HM are used in the
concerns fenugreek (Trigonella foenum-graecum L., Fabaceae), preoperative period or in the context of anesthesia. In this
which may lower blood sugar levels,6062 and when it is used period, several drugs may be administered within a short
with other herbs that may alter blood sugar levels, such as period of time and anesthetists may not be aware that their
Momordica charantia L. (Cucurbitaceae), dose adjustments patients are taking HM. The use of herbal medications among
may be necessary. Fenugreek may also increase the risk of presurgical patients may have a negative impact on perioper-
bleeding when taken with Ginkgo biloba L. (Ginkgoacea) or ative patient care.68 Indeed, herbal remedies such as Allium
Allium sativum L. (Alliaceae). sativum L., Panax species, Ginkgo biloba L., Hypericum
It is particularly important to be cautious when taking perforatum L., and Valeriana officinalis L. (Valerianaceae) can
HM in certain circumstances, such as when the risk of adverse interact with drugs and lead to many complications such as
events and interactions is great and for some categories of prolonged or inadequate anesthesia, when they are taken in the
patients who may potentially be more vulnerable to such inter- preoperative period.69,70 This is probably caused by the
actions. During pregnancy and breast-feeding, surveys show, modulation of gamma-aminobutyric acid (GABA) neurotrans-
36% to 45% of pregnant women use herbal remedies20,63; this mission.7174 In this same period, Zingiber officinale Roscoe
is probably in the mistaken belief that HM as natural products (Zingiberaceae) and Aloe vera (Liliaceae) do not prevent
are safer than chemical drugs. This new thinking also applies postoperative nausea and vomiting, as perceived by some
to the use of HM in children. Women consider herbs taken patients.75,76 Another example is the use of Piper methysticum

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Ther Drug Monit  Volume 29, Number 6, December 2007 Drug Interactions With Herbal Medicines

Forst.f. (Piperaceae) in the perioperative period: the con- compound). The information for commercial herbal products
sumption of this herbal remedy (with anxiolytic and sedative may not always be complete, when HM may often contain
properties) has potential cardiovascular effects that could a combination of ingredients, some unknown, and of
manifest in the perioperative period. Kava seems to act unregulated quality.
through inhibition of sodium and calcium channels to conduct
direct decreases in systemic vascular resistance and blood Recommendations
pressure. However, no explanation of a mechanism for this  The concurrent use of HM with prescribed drugs must take
effect has emerged from the literature. Kava may also produce into account their safety, efficacy, consistency, and
adverse neurologic effects (possibly related to its dopaminer- quality.9093 The safety of HM requires strict control of
gic antagonism)77,78 that may cause excessive periopera- the presence of adulterants, the dosage labeling, contra-
tive sedation.79 The pharmacokinetic and pharmacodynamic indications, manufacturing techniques, and a list of all
aspects of such interactions with this plant have not been ingredients. There is often no requirement to list each
studied systematically. However, pharmacodynamic herb ingredient of every herbal preparation on the label; more
drug interactions include potentiation of the sedative effect of significantly, only some of the ingredients are listed, but not
anesthetics by kava. On the other hand, kavalactones, the others that may be potentially harmful. Unfortunately, there
active component of kava extracts, have potential as inhibitors is also no requirement to precisely state the dose of active
of several enzymes of the CYP 450 system.80 So kava has the ingredients contained in herbal preparations. This should be
potential to interact with all drugs, even herbal products, which ensured through pharmacovigilance processes and strict
are metabolized by the CYP 450 enzymes. Other side effects regulatory controls.94,95
such as coagulopathies, water and electrolyte disturbances,  There is a need for an adequate regulatory framework for
endocrine effects, and hepatotoxicity were observed, in rela- herbal products to effectively protect consumers and
tion with HM consumption.81 patients.
Among cancer patients, garlic, ginkgo, echinacea  The clinical importance of herbdrug interactions depends
(Asteraceae), ginseng, St. Johns wort, and kava have been on many factors associated with the particular herb, drug,
reported as natural products that can cause potential pharma- and patient. HM should be appropriately labeled to alert
cokinetic interactions with anticancer drugs.82 HManticancer consumers to potential interactions when concomitantly
drug interactions can occur at the pharmaceutical, pharmaco- used with drugs.
dynamic, or pharmacokinetic level.83 Pharmacokinetic inter-  The widespread use of HM in pregnancy and during the
actions are the most likely. They involve changes in absorption, breast-feeding period indicates an increased need for
distribution, metabolism, and excretion of the chemotherapeutic documentation about their safety and efficacy. Unfortu-
drug. It is estimated that HManticancer drug interactions are nately, both the efficacy and safety data are largely lacking
responsible for possible undertreatment seen in cancer patients. for the majority of HM, so they can not be recommended
Induction of drug-metabolizing enzymes leads to therapeutic during pregnancy and lactation.
failure with lower plasma levels of the anticancer drugs. ATP-  Patients with cancer should avoid HM that may complicate
binding cassette drug transporters are also involved in HM- their cancer care.
anticancer drug interactions and can be one of the mechanisms  During the preoperative evaluation, physicians should be
behind these interactions. Nuclear receptor (pregnane X familiar with the potential preoperative effects of the
receptor, the constitutive androstane receptor, and the vitamin commonly used herbal medications, in order to prevent,
D-binding receptor were recently identified) plays an important recognize, and treat potentially serious problems associated
role in the induction of metabolizing enzymes and drug with their use.
transporters. Kava-kava, ginseng, garlic and echinacea are  It is important for health professionals, consumers, and
already implicated in these purposes.81 other interested stakeholder groups, including regulatory
In patients who use multiple medications, particularly authorities and suppliers of HM, to be aware of the side
elderly patients,84,85 polypharmacy and self-medication increase effects and drug interactions caused when herbal medicines
the possibilities of herbdrug interactions.86 are administered with conventional drugs. Patients should
Because of their presumed harmlessness, HM are often disclose their use of herbal medicines to their physicians and
taken by patients with chronic illness,8789 along with added pharmacists, who then will be aware of potential herbdrug
medication prescribed by physicians, and then are taken interactions. More effective communication between all
chronically. Use of both medicines simultaneously has a higher these partners is needed, and information must be accessible
potential for producing adverse events. In some situations, to all,96 which means that the responsibility of the safety
symptoms of disease or treatment are similar to those asso- information is shared. Various methods can be considered
ciated with HM adverse effects, and it is difficult to identify the for all relevant target audiences, such as involvement of the
problem.87 This could have an influence on quality of treatment. mass media and patient/consumer associations (including
Finally, some patients use crude forms of HM; in many translation into local languages where appropriate and
developing countries the source and quality of the medicines is essential for the public at large); education of health
unknown. HM are in common use and available in street professionals via the delivery of adverse- reaction bulletins
markets. Risks of interaction increase with the variability in or articles and meetings; and education about the impli-
packaging and labeling (eg, information on plant species, part cations for HM providers, academics, researchers/scientists,
of the plant utilized, type of preparation, type of marker and the pharmaceutical and herbal medicine industries.

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Skalli et al Ther Drug Monit  Volume 29, Number 6, December 2007

Communication must be an inclusive network, well were lawfully ignored or classified as dietary supplements.
structured, collaborative, and adapted to the local and This exempts many herbal medications from safety and
cultural situation. efficacy requirements and regulation. On the other hand, more
 It is imperative that physicians are aware of all medications, research and information are required (eg, preclinical, animal
both conventional and HM, that their patients are taking, in studies, premarketing controlled clinical trials, or postmarket-
order to provide the best care. This should be possible by ing surveillance) in order to guarantee the safety of patients
direct patient questioning. Physicians must regularly ask using HM.
their patients about their use of HM, particularly elderly
patients85 and those whose disease is not responding to
treatment as expected. This is important because adverse ACKNOWLEDGMENTS
reactions observed following use of conventional medicines The authors thank Mr. Bruce Hugman, communications
might in reality be due to HM or herbdrug interactions, consultant, Thailand, for his comments and suggestions
when physicians and other healthcare providers are unaware concerning this review.
of the extent of a patients self medication with alternative
therapies.97
 Herbdrug interactions must be monitored. Scientific REFERENCES
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