John Chen, Ph.D., Pharm. D., OMD, L.Ac.
The practice of medicine
is now at a crossroads: there are countless patients being treated
simultaneously with both Western and Oriental medicine. It is
quite common for a patient to seek herbal treatment while taking
several prescription medications. Safety has become a major issue.
Reasonably enough, patients want to know about compatibility and
possible interactions when taking herbs and prescription drugs
simultaneously. Such specific questions, unfortunately, are often
difficult (if not impossible) to answer. There are very few studies
published in English to document the safety and effectiveness
of combining herbs with prescription drugs. However, with some
general insights in pharmacology, one can foresee possible interactions
and thus take precautions to avoid incompatibilities.
A possible interaction
refers to the possibility that one substance may alter the bioavailablility
or the clinical effectiveness of another substance when two
or more substances are given concurrently. The net result may
be an increase or a decrease in effect of one or both substances.
Most of the possible interactions may be classified in two major
categories: pharmacokinetic and pharmacodynamic interactions.
refers to the fluctuation in bioavailability of herb-drug molecules
in the body as a result of changes in absorption, distribution,
metabolism and elimination.
Absorption is the physical
passage of herbs or drugs from the outside to the inside of the
body. The majority of all absorption occurs in the intestines,
where herbs or drugs must pass through the intestinal wall to
enter the blood. Several mechanisms may interfere with the absorption
of drugs through the intestines.
The absorption of
herbs may be adversely affected when the herbs are given together
with some drugs due to binding in the G.I. tract. Drugs such
as Questran (cholestyramine), Colestid (colestipol) and Carafate
(sucralfate) may bind to certain herbs, forming an insoluble
complex, and decrease absorption of both substances because
the size of the insoluble complex is too big to pass through
the intestinal wall.
The absorption of
herbs may be adversely affected when the herbs are given together
with some drugs that change the pH of the stomach. Drugs such
as antacids, Tagamet (cimetidine), Pepcid (famotidine), Axid
(nizatidine). Zantac (ranitidine) and Prilosec (omeprazole)
may neutralize, decrease or inhibit the secretion of stomach
acid. With the subsequent decrease of stomach acid, herbs may
not be broken down properly, leading to poor absorption in the
intestines. To minimize the risk of interaction, it is best
if the drugs and the herbs are taken separately by approximately
Lastly, drugs that
affect G.I. motility may affect the absorption of herbs.
G.I. motility is the rate at which the intestines contract to
push the content from the stomach to the rectum. Slower G.I.
motility means the herbs stay in the intestines for a longer
period of time and there will be an increase in absorption.
Conversely, faster G.I. motility means the herbs stay in the
intestines for a shorter period of time and there may be an
decrease in absorption. Drugs such as Reglan (metoclopramide)
and Propulsid (cisapride) increase G.I. motility and possibly
decrease absorption of herbs; and drugs such as Haldol (haloperidol)
decrease G.I. motility and may increase absorption of herbs.
Therefore, it may be necessary to decrease the dosage of herbs
when the patient takes a drug that decreases the G.I. motility
and increases overall absorption; and increase the dosage of
herbs when the patient takes a drug that increases the G.I.
motility and decreases overall absorption.
After absorption, herbs
or drugs need to be presented to the affected area to exert their
effect. Distribution refers to the process in which herbs or drugs
are carried and released to different parts of the body.
At the present time,
most drugs and herbs do not appear to have any clinically significant
interactions affecting distribution and can be safely taken
together. Interactions occur during the distribution phase if
the drug has a narrow range of safety index and is highly protein-bound.
For example, Coumadin (warfarin) is an anticoagulant medication
that is very highly bound to protein and has a very narrow
range of safety index. Coumadin (warfarin) interacts with various
drugs, vitamins, herbs and foods via different mechanisms. Some
known examples that interact with Coumadin (warfarin) include
aspirin, ibuprofen, vitamin K, some types of tea, green leaf
vegetables, etc. These items interact with Coumadin (warfarin)
by either enhancing its effectiveness and thus leading to prolonged
bleeding, or by decreasing its effectiveness and thus increasing
the risk of blood clots in the vessels, both of which may be
quite dangerous to the patient. This is why patients who are
taking Coumadin (warfarin) need to be exceedingly cautious when
taking herbs concurrently. Unfortunately, it is extremely difficult
to predict whether an individual herd will interact with Coumadin
(warfarin), because there are very few tests or experiments
documenting such interactions. The best precautionary measure
is close observation of the patient's condition. If the patient
shows abnormal signs of bleeding and bruises, then the dosage
of herbs may need to be adjusted and the patient's medical doctor
should be contacted immediately.
Most herbs and drugs
are metabolized by the liver to inactive derivatives. The rate
at which the liver metabolizes these herbs and drugs determines
the length of time these herbs or drugs stay active in the body.
If the liver were induced to speed up its metabolism, herbs and
drugs would be inactivated at a faster pace and the overall effectiveness
of ingested substances would be lower. On the other hand, if the
liver were induced to slow down its metabolism, herbs and drugs
would be inactivated at a slower pace and the overall effectiveness
of the substances would be higher.
In general, drugs
that induce liver metabolism do not exert an immediate effect.
The rate of liver metabolism changes slowly over several weeks.
Therefore, the effect of increased liver metabolism is not seen
until weeks after the initiation of drug therapy. Some examples
include Dilantin (phenytoin). Tegretol (carbamazepine), phenobarbitals
and rifampin. These drugs speed up liver metabolism. Therefore,
the herbs may be inactivated faster and their overall effectiveness
may be lower. Under such circumstances, the patient may need
a higher dose of herbs to achieve the desired effectiveness.
On the other hand,
drugs that inhibit liver metabolism have an immediate onset
of action. The rate of liver metabolism may be greatly impaired
within a few days. Therefore, there is a higher risk of herbs
accumulating inside the body as the function of the liver to
inactivate them is compromised. Examples of drugs that slow
down or inhibit liver metabolism include, but are not limited
to, Tagamet (cimetidine), erythromycin, ethanol, Diflucan (fluconazole),
Sporonox (itraconazole) and Nizoral (ketoconazole). Therefore,
the herbs may be inactivated more slowly and the overall effectiveness
may be prolonged. In this case, one may need to lower the dosage
of herbs to avoid unwanted side-effects.
In addition to the liver,
the kidney is also responsible for eliminating herbs and drugs
from the body. If the kidney(s) were damaged, then the rate of
elimination by the kidneys would be slowed down leading to an
accumulation of herbs and drugs in the body. Important examples
of drugs that damage the kidneys include amphotericin B, methotrexate,
tobramicin and gentimicin. As a safety precaution, it may be necessary
to lower the dose of herbs to avoid unnecessary and unwanted side-effects.
Summary of Pharmacokinetic
interactions listed in this section include both theoretical and
actual interactions. Though such interactions are possible, the
extent and severity of each interaction will vary depending on
the specific circumstances, such as dosage, sensitivity, body
weight and metabolic rate.
to the study of how drugs actually behave inside the human body.
Pharmacodynamic interactions refers to the fluctuation in bioavailability
of ingested substances as a result of synergistic or antagonistic
interactions between herb/drug molecules. Pharmacodynamic interactions
are generally more difficult to predict and prevent than pharmacokinetic
interactions. Most of the pharmacodynamic interactions known now
are documented through actual cases-as opposed to laboratory experiments.
The best way to prevent pharmacodynamic interactions is to follow
the patient closely and monitor all clinical responses including
signs, symptoms and any abnormal reactions. Examples of pharmacodynamic
interaction include additive and antagonistic interactions. An
additive effect occurs when two drugs of similar properties show
additive or exponential increase in clinical effects when given
together. An antagonistic effect occurs when two drugs of similar
properties show lessened or no clinical effect when given together.
Cases of pharmacodynamic
interactions have also been documented in Oriental Medicine. The
additive effect is generally referred to as mutual accentuation
(xiang xu) or mutual enhancement (xiang shi), such as the combination
of Gypsum (Shi Gao) and Rhizoma Anemarrhenae (Zhi Mu) to "clear
heat and purge" fire. The antagonistic effect is generally referred
to as mutual counteraction (xiang wei), mutual suppression (xiang
sha) or mutual antagonism (xiang wu), such as the combination
of Semen Raphani (Lai Fu Zi) and Radix Ginseng (Ren Shen), in
which the effect of the latter herb is decreased.
In addition, classic Chinese texts state numerous herb-to-herb interactions, such
as the Eighteen Incompatibles (Shi Ba Fan) and Nineteen Counteractions
(Shi Jiu Wei). Eighteen Incompatibles (Shi Ba Fan) is a classic
list of eighteen herb-to-herb interactions. Nineteen Counteractions
(Shi Jiu Wei) is a classic list of nineteen herbal combinations
in which the herbs counteract each other. Combinations of such
herbs will likely lead to adverse side effects and/or toxic
The list of Eighteen
Incompatibles (Shi Ba Fan) includes: Radix Glycyrrhizae (Gan
Cao) is incompatible with Radix Euphorbiae Kansui (Gan Sui),
Radix Euphorbiae seu Knoxiae (Da Ji), Flos Genkwa (Yuan Hua)
and Herba Sargassum (Hai Zao); Rhizoma Aconiti (Wu Tou) is incompatible
with Bulbus Fritillariae Cirrhosae (Chuan Bei Mu), Bulbus Fritillariae
Thunbergii (Zhe Bei Mu), Fructus Trichosanthis (Gua Lou), Rhizoma
Pinelliae (Ban Xia), Radix Ampelopsis (Bai Lian) and Rhizoma
Bletillae (Bai Ji); Rhizoma et Radix Veratri (Li Lu) is incompatible
with Radix Ginseng (Ren Shen), Radix Glehniae (Bei Sha Shen),
Radix Adenophorae (Nan Sha Shen), Radix Sophorae Flavescentis
(Ku Shen), Radix Salviae Miltiorrhizae (Dan Shen), Radix Scrophulariae
(Xuan Shen), Radix Paeoniae Alba (Bai Shao), Radix Paeoniae
Rubra (Chi Shao) and Herba Asari (Xi Xin).
The list of Nineteen
Counteractions (Shi Jiu Wei) includes: Sulfur (Liu Huang) &
Mirabilitum (Mang Xiao); Mercury (Shui Yin) & Arsenolite (Pi
Shuang); Rhizoma Euphorbiae E. (Lang Du) & Lithargyrum (Mi Tuo
Seng); Semen Crotonis (Ba Dou) & Semen Pharbitidis (Qian Niu
Zi); Flos Caryphyili (Ding Xiang) & Radix Curcumae (Yu Jin);
Nitrum (Ya Xiao) & Rhizoma Sparganii (Shan Ling); Cornu Rhinoceri
(Xi Jiao) & Rz. Aconiti Kusnezoffii (Cao Wu); Cornu Rhinoceri
(Xi Jiao) & Rhizoma Aconiti (Chuan Wu); Radix Ginseng (Ren Shen)
& Rhizoma Trogopterorum (Wu Ling Zhi); and Cortex Cinnamomi
(Rou Gui) & Hallositum Rubrum (Chi Shi Zhi).
of herb-to-drug interactions are best identified by analyzing
the therapeutic effect of the herbs and drugs. Concurrent use
of herbs and drugs with similar therapeutic actions will undoubtedly
pose potential risk of herb-to-drug interactions. The increase
in treatment effect interferes with optimal treatment outcome
as the desired effect becomes more unpredictable and harder to
obtain with precision. The highest risk of clinically-significant
interactions occurs between herbs and drugs that have sympathomimic
effects, cardiovascular effects, diuretic effects, anticoagulant
effects and anti-diabetic effects.
Herbs with sympathomimic
effects may interfere with anti-hypertensive and antiseizure
drugs. The classic example of an herb with sympathomimic effects
is Herba Ephedrae (Ma Huang), which contains ephedrine, pseudoephedrine,
norephedrine and other ephedrine alkaloids. Herba Ephedrae (Ma
Huang) may interact with many other drugs and disease conditions
and should always be used with caution in patients who have
hypertension, seizures, diabetes, thyroid conditions, etc.
of diuretic herbs and diuretic drugs may have additive or synergistic
effects, making hypertension more difficult to control or hypotensive
episodes more likely. The dosage of herbs and/or drugs must
be adjusted to achieve optimal treatment outcome. Commonly used
diuretic herbs include Poria Cocos (Fu Ling), Polypori Umbellati
(Zhu Ling), Semen Plantaginis (Che Qian Zi), and Alismatis Orientalis
Herbs with anticoagulant
effects include herbs that have blood-activating and blood-stasis-removing
functions. Such herbs may interfere with anticoagulant drugs,
such as Coumadin (warfarin), to prolong the bleeding time. Herbs
that interfere with Coumadin (warfarin) include Salviae Miltiorrhizae
(Dan Shen), Angelica Sinensis (Dang Gui), Ligustici Chuanxiong
(Chuan Xiong), Persicae (Tao Ren), Carthamus Tinctorii (Hong
Hua) and Hirudo seu Whitmania (Shui Zhi). The synergistic interaction
between herbs and Coumadin (warfarin) may be advantageous for
the patient as the dosage of both the herbs and the drugs can
be reduced without compromising clinical effectiveness. The
reduction in dosage will also decrease the frequency and severity
of side effects of the drugs. Optimal treatment, however, is
directly dependent on careful titration of the herb and drug,
cooperation from the patient, and communication between the
doctors who prescribe the herbs and the drugs.
may interfere with anti-diabetic drugs by enhancing hypoglycemic
effects. The dosage of herbs and drugs must be balanced carefully
to control effectively the blood glucose level without causing
hyper- or hypoglycemia. Herbs with definite hypoglycemic effects
include the following pairs of herbs: Anemarrhena Asphodeloidis
(Zhi Mu) and Gypsum Fibrosum (Shi Gao); Scrophularia Ningpoensis
(Xuan Shen) and Atractylodes (Cang Zhu); and Dioscorea Oppositae
(Shan Yao) and Astragalus Membranacei (Huang Qi)
Teratogenic herbs are
known to have the tendency or likelihood of causing danger or
harm to the fetus during pregnancy and thus leading to birth-defects
or spontaneous abortion. Teratogenic herbs are classified into
two categories: prohibited and use with caution.
are very potent and very toxic. The use of these herbs during
pregnancy is prohibited to avoid possible harm to the fetus.
Prohibited herbs include Semen Crotonis (Ba Dou), Semen Pharbitidis
(Qian Niu Zi), Radix Euphorbiae (Da Ji), Mylabris (Ban Mao),
Radix Phytolaccae (Shang Lu), Moschus (She Xiang), Rhizoma Sparganii
(San Leng), Rhizoma Zedoariae (E Zhu), Hirudo seu Whitmania
(Shui Zhi) and Tabanus (Meng Chong).
Herbs that should
be used with caution are herbs that are pungent and warm in
nature and have the functions to activate Qi, activate Blood
circulation, and remove blood stasis. They are also very potent
in nature and should be avoided during pregnancy whenever possible.
The use of these herbs should be limited only to later stages
of pregnancy and only when the benefits of using the herbs outweigh
the risks. Herbs that should be used with caution include Semen
Persicae (Tao Ren), Flos Carthami (Hong Hua), Rz. et Rx. Rhei
(Da Huang), Fructus Aurantii (Zi Shi), Radix Aconiti (Fu Zhi),
Rhizoma Zingiberis (Gan Jiang), and Cortex Cinnamomi (Rou Gui).
and drugs have been two very different treatment modalities
which have rarely, if ever, been used together. The line that
separates herbs and drugs, however, has been blurred in recent
decades with the increased accessibility to the lay public of different treatment
modalities. It is not uncommon for one patient to seek care
from several doctors for an ailment. As a result, a patient
may easily be taking multiple drugs, herbs and vitamins concurrently.
It becomes very difficult to predict whether the combination
of all these medications will lead to unwanted side-effects
and/or interactions. It is imprudent to assume that there will
be no interactions. On the other hand, it is just as unwise
to abandon treatment simply for the fear of possible interactions.
The solution to this situation is in the understanding of drug-drug
and drug-herb interactions. With understanding of these mechanisms,
one can recognize potential interactions and take proper actions
to prevent their occurrence.
John K. Chen,
Ph.D., Pharm.D., OMD, L.Ac. is a recognized authority on
western pharmacology and Chinese herbal medicine. He graduated
from the University of Southern California (USC) School of Pharmacy
and South Baylo University of Oriental Medicine. He also received
extensive postgraduate training in China specializing in herbology
and internal medicine.
Dr. Chen currently
teaches herbal medicine at USC, Chinese herbology at South Baylo
University, and western pharmacology at Yo San University and
Emperor's College. He is the Chair of the Herbal Medicine Committee
for the American Association of Oriental Medicine (AAOM)
and an herbal consultant for the California Association of Acupuncture
and Oriental Medicine (CAAOM).
Dr. John Chen is
the president and founder of
Evergreen Herbs & Medical Supplies
17431 E Gale Ave.
City of Industry, CA 91748
Tel: 626-810-5530 Fax: 626-810-5534
Website: www.evherb.com Email:
Copyright 1998 All
rights reserved. Written by Dr. John K. Chen, Ph.D., Pharm.D.,