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 REVIEW ARTICLE
Drug Interactions With Herbal Medicines
AU2 Souad Skalli, PhD,* Abdelhamid Zaid, and Rachida Soulaymani*
Abstract: The use of herbal medicines (HM) is on the rise among
the global population. Although the safety profile of many herbal
medicines is promising, accumulated data show evidence of
significant interactions with medications, which can place individual
patients at great risk. A range of electronic databases have been
reviewed for articles published in this field: Medline, Allied and
Complementary Medicine Database, HealthSTAR, AMBASE,
CINHAL, Cochrane Library, as well as Internet documents and
manually searched references in medical journals. In this review, we
examined the literature from 1966 to 2006 and focused on the
importance of the risk of drug interactions and potential side effects
when HM are involved. We discuss these in light of the documented
findings. A review of the problematic issues is given and
recommendations are made in order to encourage the setting up of
clinical trials on HM and herbdrug interactions.
Key Words: herbal medicines, phytotherapy, adverse effects, herb
drug interactions
(Ther Drug Monit 2007;29:000000)
INTRODUCTION
Although there are few reliable estimates of the
prevalence in use of herbal medicines (HM),1 the market for
HM continues to expand rapidly and has grown into a
multibillion-dollar industry across the world.2 The influence of
religious, sociocultural, and socioeconomic issues, traditional
practices, and belief in the use of HM is evident, particularly in
Chinese, Indian, and African societies. Documented use of
HM in Western societies is also high.3,4 Among consumers,
there is widespread belief that remedies of natural origin are
safe. Worldwide, most HM can be obtained without a pre-
scription from various sources. The majority of HM are
harmless in small doses5 (derived chemicals of many plants are
the basis of conventional drug therapies: eg, morphine/
Papaver somniferum L.; aspirin/Salix sp.; digoxin/Digitalis).
Received for publication April 11, 2007; accepted September 20, 2007.
From the *Moroccan Pharmacovigilance Centre, Rabat; and Natural
Resources Laboratory, Laboratoire des Ressources Naturelles, Faculte
des sciences et techniques, Errachidia, Morocco.
Author contributions: Review of concept and design: Souad Skalli, Rachida
Soulaymani; acquisition, analysis, and interpretation of data and drafting
of the manuscript: Souad Skalli; critical revision of the manuscript for
intellectual content: Souad Skalli, Abdelhamid Zaid, Rachida Soulaymani;
administrative and technical support: Souad Skalli, Rachida Soulaymani.
Correspondence: Souad Skalli, PhD, Moroccan Pharmacovigilance Centre, Rue
Lamfedel Cherkaoui Rabat-Instituts-Madinate Al Irfane, BP: 6671, Rabat,
Morocco (e-mail: skalli_s@hotmail.com and skallisouadcap@yahoo.fr).
Copyright 2007 by Lippincott Williams & Wilkins
Ther Drug Monit  Volume 29, Number 6, December 2007
As with all medicines, however, HM have been shown to have
adverse effects, which are related to a variety of causes,
including adulteration, mistaken use of the wrong species or
misidentification, incorrect dosing, errors in use, contamina-
tion (toxic metal, microbes, microbial toxins, environmental
pollutants), and toxic constituents (for example, aristolochic
acids, nephrotoxins found in Aristolochia species). HM affect
pharmacokinetic and pharmacodynamic properties of conven-
tional drugs and thus cause herbdrug interactions.6 Unfor-
tunately, clinicians and consumers do not always have
information that permits robust inferences about interactions
between HM and prescribed drugs.
HM chemical constituents responsible for pharmaco-
logical activity are many and complex, and the majority of
them have not been identified. Distribution of constituents is
not uniform throughout a plant. So, depending on the plant
part used medicinally, chemical constituents could vary both
qualitatively and quantitatively. For the same plant part, con-
stituents vary in relation to other factors such as intraspecies
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
used as mixtures of two or more plants with different herbal
ingredients specific to each one. In addition to the chem-
ical complexity of HM, many patients take these natural
products concomitantly with drugs prescribed by their
physicians.
For these reasons, there is a major difficulty in deter-
mining the clinical pharmacokinetic and pharmacodynamic
effects when HM are implicated. There is no doubt that there is
potential for HM to interact adversely with prescription
medicines, with danger of injury and even death. There are no
government standards for the quality of HM in most countries,
and the main problem is that little is known about them sci-
entifically. Furthermore, HM are not tested with the scien-
tific rigor required of conventional drugs. The absence of a
regulatory framework presents the major problem in pharma-
covigilance for HM.
This article highlights the evidence on herbdrug inter-
actions from a systematic literature search using electronic
databases and manual searches from 1966 to 2006. A further
goal is to discuss the particular challenges in this field and to
make recommendations to encourage the necessary clinical
trials on HM and herbdrug interactions.
For the purpose of this article, the term HM means
unconventional or alternative therapies and includes herbs,
herbal materials, herbal preparations supplied by herbalists,
and finished or manufactured herbal products found in phar-
maceutical dosage forms (tablets, capsules), as defined by the
World Health Organization.7
1
Skalli et al
MATERIALS AND METHODS
The search for literature data involved a variety of elec-
tronic databases: Medline via PubMed, Allied and Com-
plementary Medicine Database, HealthSTAR, AMBASE,
CINHAL, Cochrane Library, Internet documents, and man-
ually searched references (WHO documents and books
available in Moroccan Pharmacovigilance Centre). The review
used the search terms herbal medicines, phytotherapy, herb
drug and/or herbherb interactions, adverse effects, herbal
medicines and prescribed drugs, self-medication, herbal
medicines and pregnancy period, and pharmacokinetic and
pharmacodynamic drug interactions. They were searched in
sources from 1966 to 2006. This involved all articles written
with a focus on the risk of herbdrug interactions and potential
side effects with herbal medicines, regardless of whether they
were based on case reports, clinical trials, or other types of
investigation in humans. There was no language restriction for
literature searches. In vitro experiments were excluded. All
data were extracted, fully read, and validated by the first author.
One-hundred thirty articles were identified; 103 of them were
retained, of which 62% concerned full text and 38% were
abstract data. This article was written by the first author and
validated by the second and third authors (see footnote to
title page).
RESULTS AND DISCUSSION
Because HM use has grown significantly, it is important
to investigate the potential impact of herbdrug interactions on
patient safety and to contribute to public and scientific debate
on this matter. The potential risks resulting from such inter-
actions have received attention in several reviews and are
subject to much current interest,811 but updated information
in the absence of rigorous studies to assess the clinical
significance of herbdrug interactions is still needed to guide
practitioners involved in patient care.
Herbal medicines are used to treat many different
ailments, from common to serious and from acute to chronic,
such as diabetes, hypertension, rheumatism, cancer, asthma
and AIDS. Herbdrug interactions may occur in many
situations, even when herbal medicines are used for weight-
reduction, performance and energy enhancement, or body-
building. An example is seen with the alkaloids obtained from
species of Ephedra (Ephedraceae), administered as herbal
medicines or as products containing synthetically prepared
ephedrine and pseudoephedrine. The alkaloids, via catechol-
amines, can cause adverse cardiovascular events associated
with arrhythmias, palpitations, tachycardia, myocardial infarc-
tion, and death.12,13 Ephedrine raises blood pressure and
induces peripheral vasoconstriction. Consumption of caffeine
in Coffea arabica L. (Rubiaceae) or present in the same HM or
in drugs, and in association with ephedrine, increases the
cardiovascular risk.14,15 The danger of using ephedrine-
containing products is higher in patients who are sensitive
to the effects of sympathomimetic agents (ie, patients with
hypertension, hyperthyroidism, diabetes mellitus, psychiatric
conditions, glaucoma, prostate enlargement, seizure disorders,
and cardiovascular disease).16
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Ther Drug Monit  Volume 29, Number 6, December 2007
In general, interactions between herbal medicines and
other medicines are associated more with specific categories of
HM than others, the quality of the HM, the drug class, the
pathology and the patient population.1720 Many herbdrug
interaction case reports can be found in the literature.21 For
example: St. Johns wort (Hypericum perforatum L., Hyper-
icaceae) with its main constituents of hypericin, hyperforin,
and flavonoids, is one of the most commonly used HM for the
treatment of mild to moderate depression in Western countries.
It may have an important influence on the effectiveness, safety,
and outcome of a range of drug therapies. This is the case in
relation to serotonin reuptake inhibitors and warfarin.22,23 In
the latter case, St. Johns wort decreases the anticoagulant
effect when taken with warfarin. The possible mechanism is
hepatic enzyme induction, and there is evidence to suggest
this. Warfarin is metabolized by CYP 1A2 in the liver, which is
induced by St. Johns wort24; St. Johns wort and induction of
the human cytochrome P450 enzymes CYP 3A4, CYP2C9,
and CYP1A2.2529 St. Johns wort and cyclosporine coadmin-
istration after organ transplantation may result in cyclospor-
ine therapeutic failure in transplant graft rejection,28,30 and
St. Johns wort can increase the expression of P-glycoprotein,
with potential drug interactions.3133 P-glycoprotein is vul-
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
those with Panax ginseng species (Araliaceae) and plant
flavonoids. In the case of ginseng, it appears to decrease the
anticoagulant effect of warfarin, resulting in thrombotic
complications,23,24,3538 but the mechanism is not reported in
the literature. Matricaria chamomilla (Asteraceae) appears
to have the same interaction as ginseng with warfarin,
with respect to the coumarin constituent of this plant.37,39
Interaction between ginseng and phenelzine or alcohol is
also reported.35 In patients treated with phenelzine, ginseng
may cause headache, trembling, and manic behavior.40 Plant
flavonoids, including isoflavones, are natural components of
many plant phenolics and drug-metabolizing enzymes.41
Despite their common use, it is not widely recognized
that HM can alter the efficacy of coadministered prescription
drugs. Table 1 summarizes more examples of common herb T1
drug interactions.
The evidence from the literature that HM have phar-
macological effects and may lead to adverse interactions when
coadministered with prescription medicines has grown.4244 AU1
However, there is not enough information or adequate analysis
to estimate the magnitude of the problem.46,47 Pharmacoki-
netic and pharmacodynamic mechanisms account for herb
drug interactions. HM may affect absorption, metabolism,
distribution, and excretion mechanisms. A pharmacokinetic
interaction occurs in general when drugs (drugdrug; herbal
drug; and herbalherbal) are coadministered, and one drug
affects the metabolism of the other drug by inhibition or
induction of the specific CYP enzymes involved in its
metabolism.48,49 When HM are coadministered with prescrip-
tion drugs, there may be induction or inhibition of drug-
metabolizing enzymes. Altered drug protein binding and
altered drug excretion may also happen, although the degree of
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
transporters and metabolizing enzymes are the targets for
herbdrug interaction. Therefore, mechanism-based inhibition
of cytochromes may provide an explanation for some reported
herbdrug interactions. The best example is herbal interactions
involving cytochrome P450 enzymes.5052 This large family
of enzymes has been shown to be involved in interactions
between drugs and herbs. Pharmacokinetic interactions often
occur as a result of changes in activity of drug-metabolizing
and transporting proteins: cytochrome P450 isoenzymes
and P-glycoprotein.53 Herbal medicines, when coadministered
with prescription medicines, either induce or inhibit CYP
enzymes.54,55 This is exemplified by aristolochic acids con-
tained in Aristolochia species plants undergoing reduction of
the nitro group by hepatic cytochrome P450.56 Use of HM and
a prescription drug has the potential to decrease or increase the
effect of the drug.57 Eleutherococcus senticosus Rupt. &
Maxim (Araliaceae), for example, increased the serum
concentration of digoxin.58 However, pharmacological and
clinical data are lacking on the majority of herbal products.59
Interactions may occur between different HM them-
selves. Many examples have been reported. One of these
concerns fenugreek (Trigonella foenum-graecum L., Fabaceae),
which may lower blood sugar levels,6062 and when it is used
with other herbs that may alter blood sugar levels, such as
Momordica charantia L. (Cucurbitaceae), dose adjustments
may be necessary. Fenugreek may also increase the risk of
bleeding when taken with Ginkgo biloba L. (Ginkgoacea) or
Allium sativum L. (Alliaceae).
It is particularly important to be cautious when taking
HM in certain circumstances, such as when the risk of adverse
events and interactions is great and for some categories of
patients who may potentially be more vulnerable to such inter-
actions. During pregnancy and breast-feeding, surveys show,
36% to 45% of pregnant women use herbal remedies20,63; this
is probably in the mistaken belief that HM as natural products
are safer than chemical drugs. This new thinking also applies
to the use of HM in children. Women consider herbs taken
during gestation or breast-feeding less dangerous than
drugs.6466 Few studies have assessed the use of HM in pre-
gnancy and the factors related to this use. Herbs are taken for
venous insufficiency, lactation, gastroesophageal reflux, con-
stipation, depression, and cutaneous problems and as caffeine
substitutes. Also, HM may be taken for more serious disorders,
particularly during the first trimester of pregnancy. Unfor-
tunately, women ignore that this is the most sensitive period for
serious adverse reactions and events.
In patients who are undergoing anticoagulant pharma-
cotherapy, HM may interact with cardiovascular drugs.21
Warfarin is the most common drug involved. Herbs such as
fenugreek and Ferula communis L. can increase the risk of
bleeding (resulting in over-anticoagulation) when combined
with warfarin, heparin, and other anticoagulants, due to the
presence of coumarins.67 A case involving giant fennel has
been reported to the Moroccan Pharmacovigilance Centre.
Ginkgo biloba L. has been reported to cause spontaneous
bleeding, and it may interact also with anticoagulants and
antiplatelet agents.16 The risk appears to be higher among
patients on chronic anticoagulation therapy.
Another circumstance is when HM are used in the
preoperative period or in the context of anesthesia. In this
period, several drugs may be administered within a short
period of time and anesthetists may not be aware that their
patients are taking HM. The use of herbal medications among
presurgical patients may have a negative impact on perioper-
ative patient care.68 Indeed, herbal remedies such as Allium
sativum L., Panax species, Ginkgo biloba L., Hypericum
perforatum L., and Valeriana officinalis L. (Valerianaceae) can
interact with drugs and lead to many complications such as
prolonged or inadequate anesthesia, when they are taken in the
preoperative period.69,70 This is probably caused by the
modulation of gamma-aminobutyric acid (GABA) neurotrans-
mission.7174 In this same period, Zingiber officinale Roscoe
(Zingiberaceae) and Aloe vera (Liliaceae) do not prevent
postoperative nausea and vomiting, as perceived by some
patients.75,76 Another example is the use of Piper methysticum

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Ther Drug Monit  Volume 29, Number 6, December 2007
Forst.f. (Piperaceae) in the perioperative period: the con-
sumption of this herbal remedy (with anxiolytic and sedative
properties) has potential cardiovascular effects that could
manifest in the perioperative period. Kava seems to act
through inhibition of sodium and calcium channels to conduct
direct decreases in systemic vascular resistance and blood
pressure. However, no explanation of a mechanism for this
effect has emerged from the literature. Kava may also produce
adverse neurologic effects (possibly related to its dopaminer-
gic antagonism)77,78 that may cause excessive periopera-
tive sedation.79 The pharmacokinetic and pharmacodynamic
aspects of such interactions with this plant have not been
studied systematically. However, pharmacodynamic herb
drug interactions include potentiation of the sedative effect of
anesthetics by kava. On the other hand, kavalactones, the
active component of kava extracts, have potential as inhibitors
of several enzymes of the CYP 450 system.80 So kava has the
potential to interact with all drugs, even herbal products, which
are metabolized by the CYP 450 enzymes. Other side effects
such as coagulopathies, water and electrolyte disturbances,
endocrine effects, and hepatotoxicity were observed, in rela-
tion with HM consumption.81
Among cancer patients, garlic, ginkgo, echinacea
(Asteraceae), ginseng, St. Johns wort, and kava have been
reported as natural products that can cause potential pharma-
cokinetic interactions with anticancer drugs.82 HManticancer
drug interactions can occur at the pharmaceutical, pharmaco-
dynamic, or pharmacokinetic level.83 Pharmacokinetic inter-
actions are the most likely. They involve changes in absorption,
distribution, metabolism, and excretion of the chemotherapeutic
drug. It is estimated that HManticancer drug interactions are
responsible for possible undertreatment seen in cancer patients.
Induction of drug-metabolizing enzymes leads to therapeutic
failure with lower plasma levels of the anticancer drugs. ATP-
binding cassette drug transporters are also involved in HM-
anticancer drug interactions and can be one of the mechanisms
behind these interactions. Nuclear receptor (pregnane X
receptor, the constitutive androstane receptor, and the vitamin
D-binding receptor were recently identified) plays an important
role in the induction of metabolizing enzymes and drug
transporters. Kava-kava, ginseng, garlic and echinacea are
already implicated in these purposes.81
In patients who use multiple medications, particularly
elderly patients,84,85 polypharmacy and self-medication increase
the possibilities of herbdrug interactions.86
Because of their presumed harmlessness, HM are often
taken by patients with chronic illness,8789 along with added
medication prescribed by physicians, and then are taken
chronically. Use of both medicines simultaneously has a higher
potential for producing adverse events. In some situations,
symptoms of disease or treatment are similar to those asso-
ciated with HM adverse effects, and it is difficult to identify the
problem.87 This could have an influence on quality of treatment.
Finally, some patients use crude forms of HM; in many
developing countries the source and quality of the medicines is
unknown. HM are in common use and available in street
markets. Risks of interaction increase with the variability in
packaging and labeling (eg, information on plant species, part
of the plant utilized, type of preparation, type of marker
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Drug Interactions With Herbal Medicines
compound). The information for commercial herbal products
may not always be complete, when HM may often contain
a combination of ingredients, some unknown, and of
unregulated quality.
Recommendations
 The concurrent use of HM with prescribed drugs must take
into account their safety, efficacy, consistency, and
quality.9093 The safety of HM requires strict control of
the presence of adulterants, the dosage labeling, contra-
indications, manufacturing techniques, and a list of all
ingredients. There is often no requirement to list each
ingredient of every herbal preparation on the label; more
significantly, only some of the ingredients are listed, but not
others that may be potentially harmful. Unfortunately, there
is also no requirement to precisely state the dose of active
ingredients contained in herbal preparations. This should be
ensured through pharmacovigilance processes and strict
regulatory controls.94,95
 There is a need for an adequate regulatory framework for
herbal products to effectively protect consumers and
patients.
 The clinical importance of herbdrug interactions depends
on many factors associated with the particular herb, drug,
and patient. HM should be appropriately labeled to alert
consumers to potential interactions when concomitantly
used with drugs.
 The widespread use of HM in pregnancy and during the
breast-feeding period indicates an increased need for
documentation about their safety and efficacy. Unfortu-
nately, both the efficacy and safety data are largely lacking
for the majority of HM, so they can not be recommended
during pregnancy and lactation.
 Patients with cancer should avoid HM that may complicate
their cancer care.
 During the preoperative evaluation, physicians should be
familiar with the potential preoperative effects of the
commonly used herbal medications, in order to prevent,
recognize, and treat potentially serious problems associated
with their use.
 It is important for health professionals, consumers, and
other interested stakeholder groups, including regulatory
authorities and suppliers of HM, to be aware of the side
effects and drug interactions caused when herbal medicines
are administered with conventional drugs. Patients should
disclose their use of herbal medicines to their physicians and
pharmacists, who then will be aware of potential herbdrug
interactions. More effective communication between all
these partners is needed, and information must be accessible
to all,96 which means that the responsibility of the safety
information is shared. Various methods can be considered
for all relevant target audiences, such as involvement of the
mass media and patient/consumer associations (including
translation into local languages where appropriate and
essential for the public at large); education of health
professionals via the delivery of adverse- reaction bulletins
or articles and meetings; and education about the impli-
cations for HM providers, academics, researchers/scientists,
and the pharmaceutical and herbal medicine industries.
5
Skalli et al
Communication must be an inclusive network, well
structured, collaborative, and adapted to the local and
cultural situation.
 It is imperative that physicians are aware of all medications,
both conventional and HM, that their patients are taking, in
order to provide the best care. This should be possible by
direct patient questioning. Physicians must regularly ask
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
reactions observed following use of conventional medicines
might in reality be due to HM or herbdrug interactions,
when physicians and other healthcare providers are unaware
of the extent of a patients self medication with alternative
therapies.97
 Herbdrug interactions must be monitored. Scientific
recommendations on the use of HM and their coadminis-
tration with conventional therapy should be based on robust
scientific data rather than on the inadequate data of case
reports only. A thorough evaluation of the interaction of HM
with other medicines should be carried out; little attention
has been paid to this issue to date. Current literature data are
unsubstantiated, with conclusions based on single or limited
reports. These data are generally insufficient to predict the
incidence of herbdrug interactions. Thus, herbdrug inter-
actions !need to be investigated through greater research,
particularly by meta-analysis of prospective and clinical
studies using large population samples in order to avoid the
problems with individual susceptibility98 Prospective ran-
domized clinical trials assessing herbdrug interactions is an
urgent need.
 Exchange of data and research results among countries
must be encouraged and supported by improvement in
international conventions. Funds available for scientific and
medical research should also be directed into clinical trials
of HM.
 The inclusion of information on HM as a source of therapy
will be needed in our academic programs. Pharmacological
aspects of phytotherapy should be included in the regular
medical and pharmacy curriculum99
 Listing of safe combinations of HM and conventional drugs
can be provided as a guide to patient cares100
CONCLUSION
Crude drugs and finished herbal products are often
marketed as herbal medicines or dietary supplements for their
claimed therapeutic effects and miraculous cures. Unfortu-
nately, HM are not free of risk and interactions between these
products and prescription medications are an increasing
concern and may have significant public consequences.
However, in most cases the claims have not been substantiated
and few HM have been subjected to double-blind, randomized,
placebo-controlled clinical trials. Their potential to cause
adverse effects and interaction with conventional drugs are an
understudied field of research. It is important to be aware that
most HM fall outside of the regulatory framework and evi-
dence is generally lacking on their safety, efficacy or standards
of manufacture and control. Until now, herbal medications
6 q 2007 Lippincott Williams & Wilkins
Ther Drug Monit  Volume 29, Number 6, December 2007
were lawfully ignored or classified as dietary supplements.
This exempts many herbal medications from safety and
efficacy requirements and regulation. On the other hand, more
research and information are required (eg, preclinical, animal
studies, premarketing controlled clinical trials, or postmarket-
ing surveillance) in order to guarantee the safety of patients
using HM.
ACKNOWLEDGMENTS
The authors thank Mr. Bruce Hugman, communications
consultant, Thailand, for his comments and suggestions
concerning this review.
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