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Herb-Drug Interactions

H. Chan Thai, ND
Harborview Medical Center/University of Washington
Fall 2004

Herbal medicine has been an essential component of oriental medicine (OM), which has existed for over
two thousand years. Guided by principles of Yin Yang, Five Elements, Organs and Meridians, the
practice of oriental herbal medicine has not changed significantly (please click here to view TCM
theories). Herbal prescriptions comprise the vast majority of OM practice in China and Southeast Asia.
Many city hospitals in China, Taiwan, and Korea have integrated clinics with dispensing labs that prepare
herbal concoction. Scientific verification and applications beyond traditional prescriptions are beginning
to be explored in the West. For example, typing Chinese herbal medicine and Chinese herbal medicine
AND pharmacology on sciencedirect.com yielded 180 and 80 studies respectively. A similar search on
nlm.nih.gov showed a total of 524 studies; narrowing this search to Chinese herbal medicine and cancer
resulted in 110 articles. Among this research includes documentations on herb-herb and herb-drug
interactions.

This paper focuses on commonly recognized Western botanicals as well as Chinese herb-drug
interactions. It is hoped that this area of medicine which heavily depends on the cooperation of
supplement/pharmaceutical industry, patients, and practitioners across specialties will mature to the point
where one can safely go back and forth between traditional and modern medicine. Until then it is hoped
that clinical guide such as this will help avert unnecessary interactions.

While literature emphasizes recent development in this area, it is worthy to acknowledge that herbal
interactions were documented in ancient traditional TCM texts, by case studies and traditional theories.
For example, in all formulae, warm herbs are balanced by cool herbs and vice versa. TCM herbalists have
to carefully prescribe formulae based on disease manifestation and the patient’s energy ‘Qi’. Therefore,
cold or hot drugs are rarely recommended for extended use-it is believed that they can deplete the body’s
energy ‘Qi’. In Western medicine, laxatives and steroids are typical examples of cold and hot drugs. In
addition to utilizing the herbs’ energetic property TCM practitioners also rely on the tastes of an herb as
part of a therapeutic guide. For example, sweet herbs like licorice (glyccerhiza) are thought to be neutral
and nourishing so it is often used in TCM herbal formulae to ameliorate side effects of other ingredients.

Traditional herbal texts recognized a number of herb-herb interactions as summarized below:

1. 18 incompatible combinations: This includes three herbs (aconite, licorice, and veratrum) with 6 other
herbs. Their combinations would lead to herb-to-herb interactions and/or toxicity.

R. Glycerrhiza (Gan Cao) Incompatible R. Euphorbiae Kansui (Gan sui), R. Euphorbiae seu
combinations Knoxiae (Da ji), Fos Geukwa (Yuan Hua), and
Herba sargassum (Hat zao)
Rhizoma Aconite (Wu tou) Bulbus fritillariae cirrhosac (Chuan bet mu), bulbus
fritillariae thundergii (Zhe bet mu), Fructus
trichosanthis (Gua leu), Rhizoma pinelliac (Ban
xia), R. Ampelopsis (Bat lian), and Rhizoma
bletillae (Bat ji).
Rhizoma et Radix veratri (Li lu) R. ginseng (Ren shen), R. Glehniae (Bet sha shen),
R. adenophorae (Nan shi shen), R. scrophulariae
(Xuan she), R. paeoniae alba (Bat shao), R.
paeoniac Rubra (Chi shao), and Herba asari (Xi
xin).
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2. Herbs with teratogenic (birth defects) effects:

Hirudo seu whitmania Shui zhi


Moschus She xiang
Mulabris Ban mao
Radix euphorbiae Da ji
Radix phytolaccae Shang lu
Rhizoma sparganii San leng
Rhizoma zedoariae E Zhu
Semen crotonis Ba dou
Semen pharbitidis Qian niu zi
Tabanus Meng chong

3. Herbs with potential for toxic effects: These herbs are very strong Qi and Blood movers and can
certainly cause side effects if used inappropriately. They should also be avoided during pregnancy.

Semen persicae Tao ren


Flos carthami Hong hua
Rhizoma and Radix Rhei Da huang
Fructus aurantii Zi shi
Radix aconite Fu zhi
Rhizoma zingiberis Gan jiang
Cortex cinnamomi Rou gui

Oriental herbal medical principles are fascinating and cannot be fairly addressed in this space. In general
TCM herbal formulation often consists of 4-12 ingredients. Each herb plays an important role in the
delivery and action of the formula. For example, certain ingredients assist in delivering the main herb to
the organ or meridian while other ingredients act to reduce the side effects or to augment the desire effect.
Oriental herbal medicine utilizes plants, minerals, insects, and animal products. Rarely do we find herbs
being prescribed as a single agent.

However, consuming herbal medicine has not been without risks. Some Chinese herbs have been reported
to contain heavy metals and/or adulterated with western drugs. For example, PC-SPES was recalled in
California because it may have been contaminated with warfarin, alprazolam, and diethylstilbesterol (10).

Recent national surveys have shown that trends for complementary and alternative (CAM) usage have
increased steadily among adults over the past 50 years. About 60 million Americans (1 in 5) use CAM
therapy, and this trend is expected to significantly increase if insurance coverage for CAM increases in
the future. It was estimated that 20% of patients regularly taking prescription drugs were also taking
herbal or nutritional supplements, suggesting that about 15 million Americans are at potential risk for
herb-drug interactions. Also, about a third of patients reported they seek CAM therapies for health
promotion and disease prevention (1,2).

These studies were conducted among English speakers. Although no formal studies to date exist for
ethnic minorities, it is expected that a higher percentage of Asian Pacific Islanders rely on their traditional
herbal medicine and that many of them use both traditional and Western medicine concurrently or even
interchangeably.

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Evidence for herb-drug interactions in humans has been inconsistently reported through case studies. One
review 2/3 of the 108 case reports was classified as ‘unable to be evaluated’, which meant they lack
critical information to explain other possibilities. For example, many the case reports focused solely on
the agents involved and failed to include relevant information such as: patient history; concurrent
diseases, conditions, or medication associated with adverse event; concomitant medications; description
of interaction; alternative explanations; chronology, and time sequence of drug administration etc (3,4).

One of the challenges in integrative medicine at the presence is that most supplements available over-the-
counter are not standardized. Purity and potency standards are only available for a small selection of
herbs. To further complicate this matter, patients may take supplements from different manufacturers (5).

Likewise similarities in names and appearance have caused some Chinese herbal products to contain
misidentified plants. Pharmaceutical drugs and a significant level of heavy metals were also found in
some herbal patents (4). Without a standard for purity and potency, the possibilities for interactions
increase greatly for drug-herb, herb-herb, or reactions to contaminants. Besides posing risks of toxicity for
patients, it is also difficult to verify reports on herb-drug adverse reactions due to numerous unknown
variables.

The greatest potential for adverse effects between herb-drug combinations occurs when the followings are
combined:

• Sympathomimic (anti-seizure), and Cariovascular drugs: Ephedra (Ma huang) contains


ephedrine, and pseudoephedrine that interferes with this class of drugs.
• Diuretic drugs: A variety of herbs can increase or decrease this effect. The most
commonly used oriental herbs for their diuretic effects include:, Polypori Umbellati (Zhu
ling), Semen plantaginis (Che qian zi), and Alismatis orientalis (Ze xie), Akebia trifoliata
(Mu Tong), .
• Anti-diabetic drugs: Anemarrhena asphodeloidis (Zhi mu), Gypsum fibrosum (Shi gao),
Scrophularia ningpoensis (Xuan shen), Atractylodes (Cang Zhu), Dioscorea oppositae
(Shan yao), and Astragalus membranacei (Huang qi).
• Anti-coagulating drugs: Because Coumadin (Warfarin) interacts with a wide range of
herbs, it is best to avoid combining Coumadin with all herbs unless the patient has
guidance from an experienced health professional. TCM herbs with the greatest potential
for interfering with anti-coagulants includes: Salviae miltiorrhizae (Dan shen), Angelica
sinensis (Dang gui), Ligustici chuanxiong (Chuan xiong), Persicae (Tao ren), Carthamus
tinctorii (Hong hua), and Hirudo seu whitmania (Shut zhi). Likewise, patients should also
monitor their green vegetables intakes when they are on anti-coagulant therapy.

In addition to the above guide and case reports, it is possible to predict when herb/drugs interact by
knowing their pharmacokinetic properties, and their pharmacodynamic behaviors. For our purpose,
pharmacokinetic properties entail changes in absorption, metabolism, and elimination of the drugs/herbs
whereas pharmacodynamic behaviors refer to how the herb/drug interacts inside the body (synergistic or
antagonistic). In general, herb/drug that alters the stomach pH (anti-acids), or intestinal motility
(laxatives) will have an effect on absorption. Drug/herb metabolism occurs principally in the liver. The
duration (life-span) of an herb or drug in the body depends on whether the liver’s metabolism is induced
or inhibited. An herb lasts longer in the body if its metabolism is inhibited by another drug; likewise, it is
excreted faster if one’s liver metabolism is induced. Further, drug/herb elimination primarily occurs at the
kidneys and is affected by the individual’s kidneys function or by drugs’ toxic side effects. Lastly, the
extent to which an herb-drug interacts depends on the individual’s health condition, age, body weight,
metabolic rate, and dosage (11).

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Commonly used herbs taken by older adults and their potential for herb-drug interactions.

Herbs Drug Interactions Adverse potential


Bupleurum spp. • None known • Some side effects of this herb include
(Chinese Thoroughwax, Chai increased bowel movement, and
Hu) drowsiness.

Primary use: symptoms


associated with common
cold, flu, liver disorders…

Primary action: Bupleurum


stimulates the immune
system
Danshen (Salvia Warfarin Decreases warfarin clearance and increases
miltiorrhiza) its bioavailability. Case report of
hemorrhage.
Primary usage: promotes
blood flow and treat
cardiovascular diseases i.e.
angina pectoris, acute MI.

Primary actions: scavenges


free radicals, inhibit platelets
aggregration, and promote
vasoactive.
Dong Quai • Warfarin • Dong Quai is safe for most adults.
(Angelica Sinensis, Dong Women who are pregnant or breast-
Gui, Chinese Angelica, Tan feeding should not take it without
Kuei) consulting their healthcare provider.
• Women with hormone sensitive cancers
Primary use: It is most such as breast, uterine, or ovarian
often used in oriental cancer and those with endometriosis or
medicine for menstrual uterine fibroids should also exercise
problems. caution.

Dong Quai can also be


widely found in traditional
formulation for pain.
Ephedra Sinensis MAOI, caffeine, Ephedra and MAOI can cause dangerously
(Cao Mahuang, Ma huang, decongestants, stimulants high blood pressure. FDA proposed a
Yellow astringent) dosage limit of 8 mg every 6 hours (or a
total of 24 mg per day) and not more than 7
days of continuous use.

Ephedra, by itself, is not recommended for


most people. It is never used alone in TCM.

Ephedra sinensis cont. People with the following Risks of prolonged usage and high dosages
condition should not take consumption include: high blood pressure,
Primary use: Ma huang Ephreda: Chest pains, stroke, heart attacks, seizures, irregular heart
is well known as a cardiovascular disease, beat, loss of consciousness, and death. 4
weight loss pill in the anxiety,http://ethnomed.org/clin_topics/herbal_medicine/herb-drug_rev.pdf
eating disorder, and
West (i.e. herbal fen- thyroid problems. Less severe adverse symptoms include:
Ginger cont. Ginger may interfere with
medications for controlling
…and loss of appetite. blood sugar, blood pressure,
and stomach acid.
Ginseng (Panax species) Warfarin Decreased INR
Alcohol Increased alcohol clearance 5
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Primary use: vigor, Phenelzine; MAOI Headache, tremor, mania
well-being and longevity,
Kava cont.

Kava may INCREASE


RISKS of liver damage when
combined with a number of
medications: acarbose, 6
amiodarone, atorvastatin,
http://ethnomed.org/clin_topics/herbal_medicine/herb-drug_rev.pdf
diclofenac, isoniazid,
itraconazole, ketoconazole,
St. John’s Wort SJW can significantly By far, SJW has been the most commonly
(Hypericum decrease availability and reported herb causing herb/drug interactions.
perforatum) absorption of many drugs Short-term use appears to be safe for most
by inducing liver enzyme consumers. In some patients, SJW can cause
Primary use: mild- CYP 450 and inhibiting, insomnia, restlessness, vivid dreams, anxiety,
moderate depression, including drugs for: irritablility, stomach upset, fatigue, dry mouth,
possibly effective for dizziness, headache, and tingling.
anxiety. • SSRI’s 7
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• AIDS SJW can cause skin to become extra sensitive
Primary actions: • Anxiety to the sun, especially in light-skinned
In summary, patients should not try to mix drugs that have a narrow therapeutic range (digitalis,
theophylline, lithium, and warfarin) with potassium lowering herbs (licorice, and aloe), herbal stimulants
(ephedra, caffeine, guarana, green tea), and antiplatelet herbs (Ginkgo, bilberry leaf, ginger, black cohosh,
and Chamomile) (11).

Just as important, if patients insist on integrating herbal medicine they must be taking their medication
and herbs consistently in order to avoid severe under or overdose.

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Using foods to balance internal disharmonies:

In addition to herb-drug interactions, food can and do also interact with medication. Traditional Chinese
medicine views food the same way it views medicine. For example, all foods and drinks are classified by
their energetic properties such as hot, warm, neutral, cool, and cold (Yin and Yang). Further, foods are
also graded by their tonic potential versus their draining effects on the body such as excessive heat, cold,
damp, or dry. For example, rice is considered a tonic whereas cream is considered cold and damp. Thus,
TCM thinks about food as medicine and their potential for benefits as well as interactions with herbal
therapy. When a patient with excessive heat, cooling herbs are prescribed and instructed to avoid dry or
hot food i.e. chips, deep-fried food, or spicy food. Instead, the patient is advised to eat mung bean or
mung bean sprouts. Click here for more information on food as medicine.

Working with patients who use complementary and alternative medicine (CAM) and
conventional medicine:
With no clear guidelines for integrating CAM and conventional medicine, it is important for clinicians to
foster an open dialogue with their patients. Eisenberg and colleagues reported that about 60% of the
people surveyed did not discuss their CAM use with their primary care physicians (2). This lack of
communication is expected to be more prevalent among immigrant communities due to language and
cultural barriers. For example, many patients do not want to appear disobedient toward their providers by
admitting that they are seeking other treatments, or think their providers care or need to know about their
traditional practices.

Additionally, providers should be aware of reasons why their patients seek out CAM therapies. For
example, 1) conventional therapies no longer provide relief or are producing unwanted side effects; and 2)
no specific conventional therapy exist or the treatment plans are contrary to patient’s belief (6).
Sometimes, a misunderstanding of the instruction of how to take the medicine, urgency of their
conditions, or difficulties in filling the prescriptions can pose barriers for proper health care among
immigrant communities.

Further, since CAM therapies have been an integral part of Southeast Asian’s health promotion and health
maintenance practice, they do not generally associate potential for toxicity when combining CAM
therapies with western drugs. Hence, providers should approach this discussion with sensitivity and
openness (6).

Below are suggestions for exploring CAM therapies with Vietnamese patients:

Acknowledge that certain traditional health practices are common in their communities. For example, in
Southeast Asia, ‘coining’ and ‘cupping’ are often used at home for minor aches, pain and colds. These
techniques often leave bruise-like appearances on the skin. Herbal tonics and dietary therapies are also
commonly used for health maintenance. Some therapies clearly offer relieves, others are harmful
especially when combined with western medication. The effects of combining both traditional and
conventional therapies may take weeks or months to be apparent. Certain combinations can be
detrimental.

Integrative medicine is a young practice, still needing a safe practice guideline, and resources for
clinicians and patients alike. When working with patients utilizing CAM and western medicine, a step-by-
step strategy is recommended. This includes: 1) Asking patients to identify the principle complaint and
maintaining a symptom diary; 2) Discussing patient’s expectations and preferences, and reviewing safety
and efficacy issues; 3) Identifying a suitable licensed provider; 4) Establishing a treatment strategy with
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CAM provider and requesting documentation; and 5) Scheduling follow-up visit to review treatment plan
(6).

References:

1. Eisenberg, M. David, M.D; et al. Unconventional medicine in the United states. N England J Med.
1993 ; 328 :246-252.
2. Eisenberg, David M. M.D; et al. Trends in Alternative Medical use in the United States, 1990-
1997: Results of a Follow-up National Survey. JAMA, November 11, 1998-Vol 280, No. 18.
3. Fugh-Berman, Adriane and Ernst E. Herb-drug interactions: Review and assessment of report
reliability. Blackwell Science Ltd Dr J Clin Pharmacology, 2001-Vol. 52; 587-595.
4. Fugh-Berman, Adriane. Herb-Drug interactions. Lancet, 2000; 355: 134-38
5. Cupp, Melanie J. Pharm.D. Herbal Remedies: Adverse Effects and Drug Interactions. American
Academy of Family Physicians, March 1, 1999. 1239-47
6. Eisenberg, M. David, MD. Advising patients who seek alternative medical therapies. Annals of
Internal Medicine, Juy 1997; Vol 127 issue 1; 61-69.
7. Williams, M. Cynthia, CAPT, MC, USN, Using Medications Appropriately in Older Adults.
American Family Physician, November 2002; Vol 66, no 10; 1917-1924.
8. Valli, Georginanne, MD, Giardina, V. Elsa-Grace, MD, FACC. Benefits, adverse effects and drug
interactions of herbal therapies with cardiovascular effects. J. American College of Cardiology,
2002; Vol. 39, No. 7, 1083-1095.
9. Natural Medicines Comprehensive Database. Consumer Information and Education.
http://www.naturaldatabase.com.
10. Bonakdar, A. Robert, MD. Herb-drug interactions: What physicians need to know. Patient Care
Archive. January 2003, 1-13.
11. Lambrecht, E. Jason, Pharm.D. et al. Review of Herb-Drug interactions: Documented and
Theoretical. http://www.fibrohugs.com/html/warning_herb-drug_reaction.html
12. Chen, John, Pharm.D, Recognition and Prevention of herb-Drug Interaction.
www.acupuncture.com/Herbology/drug.htm

Additional resources:
1. Steyer E. Terrence, MD. CAM: a Primer. Family Practice Management. March 2001,37-42.
2. Abele W. PhD. Herbal medication: Potential for adverse interactions with analgesic drugs. Journal
of Clinical Pharmacy and Therapeutics. 2002, 27:391-401.
3. Stedman, Catherine, MB.ChB, FRACP. Herbal Hepatotoxity. Seminars in Liver disease/Vol 22,
No 2, 2002, 195-206.

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