Prevention of Herb-Drug Interaction
By 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 bioavailability 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 into two major categories: pharmacokinetic and pharmacodynamic
interactions.
Pharmacokinetic Interactions
Pharmacokinetic interaction
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
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 the 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 two hours.
Lastly, drugs that affect the
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 a 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.
Distribution
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 herb 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.
Metabolism
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.
Elimination
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
The 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.
Pharmacodynamic Interactions
Pharmacodynamic
refers to the study of how drugs actually behave inside the human body. A pharmacodynamic
interaction 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.
Herb-to-Herb Interactions
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 reactions.
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).
Herb-to-Drug Interactions
Pharmacodynamic
types 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 anti-seizure 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.
Concomitant use 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 (Ze Xie).
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.
Anti-diabetic herbs may interfere with
anti-diabetic drugs by the enhancing hypoglycemic effects. The dosage of herbs
and drugs must be balanced carefully to effectively control 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
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.
Prohibited herbs 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 (Zhi
Shi), Radix Aconiti (Fu Zi), Rhizoma Zingiberis (Gan Jiang), and Cortex Cinnamomi
(Rou Gui).
Conclusion
Historically, herbs and drugs have been two very
different treatment modalities that 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 Lotus Herbs, and is available for medical
consultations through the Lotus Herbal Consultation Line.
Tel: (626) 916-1070;
Fax: (626) 917-7763;
Lotus Herbs: 1124 North Hacienda Blvd. La Puente,
CA 91744.
Copyright 1998 All rights reserved. Written by Dr. John K. Chen,
Ph.D., Pharm.D., OMD, L.Ac.