lisa Cranwell-Bruce

Herb-Drug Interactions

n novelist Kathy Lynn Emerson's Face Down mysteries, her protagonist Susanna, Lady Appleton, is described as a gentlewoman and herbalist in 16"^ century England. Lady Appleton even wrote a "cautionary herbal" to assist good housewives not to poison their families and servants with common herbs (Emerson, 2007). Her near contemporary in real life was Nicholas Culpepper, a 17th century English physician. He wrote an herbal guide, originally published
as The English Physician, in 1652.

tions are more likely to interact with your patients' prescribed medications? Are you counseling your patients about potential drug-herb interactions? The most popular herbals being purchased and taken by patients today will be reviewed, and common interactions with prescriptive medications described.

Factors in Herb-Drug interactions

The World Health Organization reported that 11,000 species of plants are used medicinally, with 500 of these plants and herbs used in complementary medicine (Zhou, 2006). Americans' use of herbal medications continues to rise; approximately $20.1 billion was spent on herbal preparations in 2003, with about 16% of Americans reporting that they were using both herbals and prescriptive medications at the same time (Spencer, 2004). Hoblyn and Brooks (2005) reported that 23% of Americans over age 65 use herbal products, but two-thirds of them do not tell their health care providers about their use. An AARP survey of 1,559 individuals over age 50 similarly found that 69% of respondents did not discuss using herbal therapy with their health care providers (Kuehn, 2007). Another study of patients with arthritis (Bush et al., 2007) reported that 55% did not report their use of alternative medications because either their health care providers did not ask about any use or they were afraid of disapproval.

Culpeper's work was considered very influential at the time and is still used because a great deal of the information remains current to this day (Bibliomania, n.d.). Herbs and other botanicals have been used for centuries by health practitioners and patients alike. Libster (2002) noted that nurses historically practiced independently using herbs and plants as part of their treatment, and also taught their patients how to use plants to improve their health. Use of herbal preparations remains a very important point of patient education for nurses. When taking a health history, do you ask your patients about both prescriptive and complementary medications and treatment? Do you know which popular herbal prepara-

Several key points contribute to understanding the interaction potential between herbal products and many prescriptive medications. First, dietary supplements were defined by the Dietary Supplement and Health Education Act of 1994 to include products, such as herbals, weight management products, specialty supplements, and other oral dosage forms, developed to supplement an individual's diet (Chavez, Jordan, & Chavez, 2006). They therefore are not regulated by the Food and Drug Administration (FDA) in the same manner as prescription and over-the-counter medications; instead of following good manufacturing practices for drugs, then, producers of supplements follow good manufacturing practices for food. Although they are not allowed by law to market a product known to be unsafe, supplement manufacturers also do not have to provide the FDA with proof that a product is safe or effective. Once a product reaches store shelves and the consumer, the burden is on the FDA to prove that it is unsafe, remove it from marketing, and prohibit its use by consumers. The next important review point is the cytochrome P-450 system, also know as the CYP-450 system. These microsomal enzymes cissist with liver metabolism. Three of these cytochrome families (CYPl, CYP2, and CYP3) are involved in drug metabolism (Aschenbrenner & Venable. 2006). Haller (2006) reported that alteration of the CYP 450 enzyme activity by the herbal

Usa Cranwell-Bruce, MS, RN, FSP-C, is a Clinical Instructor, Byridine F. Lewis School of Nursing, College of Health and Human Services, Georgia State University, Atlanta, GA.

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product is the reason for many herb-drug interactions. One last point related to interaction is the body's medication transport system, which carries drugs from one side of the cell to the other. P-Glycoprotein is one multidrug transporter. It is present in the cells of many systems and organs, particularly the kidneys and liver where it assists with elimination (Lehne, 2007). The drugherb interactions occur because the herbs will influence the rate of transportation of the drug and its metabolism (Tomlinson, 2006). Common Herbs Bressler (2005) identified seven herbs commonly sold in the United States; ginkgo biloba, St. John's wort, ginseng, kava, saw palmetto, garlic, and echinacea. For the first five, documented information is available on efficacy and drug interaction. For garlic and enchinacea, the available literature at the time of publication did not support the claims of the herbs. Sego's (2006d) list of the top 10 herbal supplements had notable similarities but also included feverfew, valerian, and ginger. If you have looked in your own medication cabinet or spice rack or walked the aisles of your local drug store, you cannot help but agree with the list of commonly used herbs. St. John's wort is used commonly to treat the symptoms of depression and nervous disorders, as well as diarrhea and urinary tract symptoms; it has been used for centuries by various cultures in various forms (Libster, 2002). Sego (2006c) noted that its efficacy for treating major depression did not surpass placebo in large studies by the National Institute of Health, but a review of European studies did show efficacy in moderate depression. This herbal product has many identified drug interactions, and Indeed has been noted as the product with the most reported and documented interactions (Tirona & Bailey, 2006). It is believed to have gained this designation because it induces both CYP 3A4 and intestinal p-glycoprotein (Chavez et al, 2006). Some 13 categories of drugs

have been identified that interact with St. John's wort, or have reduced efficacy when taken with it (for example, antidepressants, antihypertensives, anticoagulants) ("Risky Herb-Drug Interactions," 2007). This herb also may increase the chance of side effects in drugs such as tricyclic antidepressants and triptans. Tirona and Bailey (2006) suggest that the number of documented drug interactions should prompt a warning label or a pharmacist consult before an individual is able to purchase St. John's wort. While this intervention may seem extreme for those patients who believe that natural is best, it is appropriate to recommend that patients taking a prescriptive or over-the<ounter medication consult with a pharmacist before adding any new herbs or other medications to their regimens. Kava (or Kava kava) is a member of the pepper family that has been used for its psychoactive and pain management properties, and has a muscle relaxant effect. It has been reported to help with sleep in regular doses, and to serve as a stimulant in smaller doses (Libster, 2002), However, the FDA did issue a consumer advisory regarding kava dietary supplements in 2002 due to the risk of severe liver injury, including hepatitis, cirrhosis, and liver failure, with one case of a previously healthy patient requiring a liver transplant (Center for Food Safety and Applied Nutrition, 2005). Literature also includes one report of a semi-comatose state that occurred in a patient when kava was administered along with alprazolam (Xanax) (Zhou, 2006). Saw palmetto is seen in abundance in the southeastern United States. Male patients particularly use it to help with the symptoms associated with benign prostatic hyperplasia (BPH); it is widely recommended by urologists in Europe, to the extent that 90% of prescriptions for BPH in Europe include saw palmetto (Libster, 2002). Controlled trials in the United States have proven its efficacy (Bressler, 2005), but it may interact with hormonal drugs such as estrogens and oral contracep-

tives ("Risky Herb-Drug Interactions," 2007). Sego (2006b) reported that saw palmetto is generally well tolerated but, as with any medication or supplement, allergies and liver and kidney function should be confirmed. Garlic is common is most households as part of delicious meals. The reported health benefits of garlic date to 1550 BC, including use as a disinfectant, stimulant, and strength enhancer (Sego, 2006a). Currently, garlic is used to reduce the risk of cardiovascular disease, reduce serum lipids, and lower both blood pressure and blood glucose (Libster, 2002). The question with garlic concerns how much is enough. Some may think that excessive garlic would be avoided because of its strong odor, but many patients use supplements in capsule or gel tablet form to avoid the odor in their breath and perspiration. Izzo (2005) reported that patients who took saquinavir (Invirase, Fortovase) with repeated doses of garlic had lower plasma concentrations of the drug, and also noted that garlic interfered with acetaminophen (Tylenol^ and anticoagulant effectiveness. Constant use of garlic and garlic supplements can cause gastrointestinal irritation, diaphoresis, bleeding disorders, and allergic reaction (Sego, 2006a). Ginkgo biloba has been used in China for thousands of years and has gained popularity in the United States to prevent memory loss, help prevent or delay Alzheimer's disease, and improve vascular diseases and conditions (Sego, 2007). In Europe, the plant itself is not used; rather, an extract has been developed and is now one of the top five herb prescriptions in Germany (Libster, 2002). Sego (2007) reported in a review of the literature that ginkgo biloba had a positive effect on cognition. It is being tested currently in a large clinical trial by a division of the National Institutes of Health (Bush et al., 2007). Interaction potential exists between ginkgo biloba and commonly used drugs, such as acetaminophen, hydrochlorothiazide, tramadol (Ultram), simvastatin (Zocor), amitriptyline (Elavil),

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aspirin, losartan (Cozaar), and lansoprazole (Prevacid) (Bush et al., 2007).

Nursing Implications
What does this mean for nurses who are counseling their patients about the use of herbs and allopathic medicines? Nurses should always instruct patients to report any prescriptive medication, herbal, or dietary supplement they are using in order to explore possible drugherb interactions. Nurses also need to discuss with patients why they are using herbal medications; what are their desired outcomes? As with any medication, patients should be cautioned to be alert to possible allergic reactions and potential side effects. Some drugs are known to interact with many herbal medications. Warfarin (Coumadin) is one of the most notable and is known to interact with many categories of drugs (Bristol Myers Squibb, 2006). It also interacts with popular foods, such a grapefruit juice, soy milk, seaweed, oily fish, and food with high vitamin K content (Holbrook et al., 2005). Izzo (2005) reported problems with over-coagulation or under-coagulation known to exist with at least 17 herbs, including garlic, St. John's wort, ginkgo, ginseng, and cranberry. Patients receiving warfarin were also cautioned to be alert to possible problems with herbal mixtures that may be prepared with vitamin K-rich products, such as green tea. A patient survey found that many patients with diabetes also used herbal supplements to help control their blood glucose (Bush et al., 2007). One problem with this strategy was the risk for hypoglycemia; this can prompt nurses to discuss with patients the possible need for dosage adjustment of hypoglycemic drugs, as well as to ask patients about use of herbs and explore potential adverse drugherb interactions. Haller (2006) recommended cautioning patients who are using stimulatant or sedative drugs to use herbs cautiously with these drug groups. Herb-drug interaction has been reported with commonly prescribed drugs, such as birth control pills, antibiotics, cancer

treatments, and heart medications (Spencer, 2004). A potential herbdrug interaction exists between many prescriptive medications and commonly used herbs. Tomlinson (2006) compared the discovery of drug interactions with grapefruit juice to the ongoing reports of drug-herb interactions; both allow health care providers to counsel patients appropriately.

Conclusion
As additional herb-drug interactions are discovered and reported, it becomes increasingly critical for the nurses to explore herbal usage with their patients and provide cautions. Patients also should be reminded that the FDA does not regulate herbal medication; the safety of herbal preparations is not assured, and possible contaminants in herbal preparations may cause allergic reaction or even death (Gupta & Abedin, 2007). The nurse also should explain to the patient that standardization is not common in herbal preparations; the amount of the actual herbal present in a preparation or compounded form may vary by the preparer, the brand, or alterations from binders or additives (Shan, 2005). High-risk groups, such as patients preparing for surgery, those with diabetes, patients who require a serum-monitored drug, or those who have had a sudden adverse reaction to a long-term medication, should be asked about herbal preparations and counseled appropriately regarding their use (Bush et al., 2007; Izzo, 2005). Collaborating with a pharmacist also will help to avoid potential herb-drug interactions for patients.
References Aschenbrenner, D.S., & Venable, S.J. (2006). Drug therapy in nursing (2* ed.). Philadelphia: Lippincott, Williams & Wilkins. Bibliomania, (n.d.). Cuipeper Retrieved October 1,2007, from htlp://www.bibliomania.oom/ 2/1/66/113/frameset.html Bressler, R. (2005). Herb-drug interactions. Interactions between Ginkgo biloba and prescription medications. Geriatrics. 60(4), 30-33. Bristol Myers Squibb. (2006). Coumadin (warfarin sodium) full prescribing information (Vol. 2007). Princeton, NJ. Bush, TM., Rayburn, K.S., Holloway, S.W., Sanchsz-Yamamoto, D.S., Allen, B.L., Lam, T, et al. (2007). Adverse interactions between herbal and dietary sub-

stances and prescription medications: A clinical survey. Alternative Therapies in Heaith & Medicine, 13{2). 30-35. Center fcr Food Safety and Applied Nutrition. (2005). Letter to heaith care professionais: FDA issues consumer advisory that i<ava products may be associated with severe iiver injury. Retrieved October 25, 2007, from http://www.cfsan.fda.gov/ -dms/ds-ltr29.html Chavez, M.L., Jordan, M.A., & Chavez, PI. (2006). Evidence-based drug herbal interactions. Life Sciences, 7S(18), 2146-2157. Emerson, K.L. (2007). Kathy Lynn Emerson, writer. Retrieved October 10. 2007, from http://www.kathylynnemerson.com Gupta, S., & Abedin, S.A. (2007). Buyer beware. Time. 169. 58. Hailer, C. (2006). Clinical approach to adverse events and interactions related to herbal and dietary supplements. Clinical Toxicology 44(5), 605-610. Hoblyn, J.C, & Brooks, J.O. III. (2005). Herbal supplements in older adults. Geriatrics. 60{2). 18-23. Hoibrook, A.M., Pereira, J.A., Labiris, R., McDonald, H., Douketis, J.D., Crowther, M., et al. (2005). Systematic overview of warfarin and its drug and food interactions. Archives of Internai Medicine. 16500), 1095-1106. Izzo, A.A. (2005). Herbal drug interactions: An overview of the clinical evidence. Fundamental & Ciinicai Pharmacology. 19(1), 1-16. Kuehn, B.M. (2007). Seniors mum on herbals. JAMA: Journal of the American Medicai Association. 297{8), 799-799. Lehne, R.A. (2007). Pharmacologytornursing care (6'" ed.). St. Louis: Saunders. Libster, M. (2002). Delmar's integrative herb guide for nurses. Albany, NY: Delmar Thomason Learning. Risky herb-drug interactions. (2007, January). Consumer Reports on Heaith. 19, 10. Sego, S. (2007). Alternative meds update: Ginkgo biloba. The Ciinicai Advisor, 10{9), 115-116. Sego, S. (2006a). Alternative meds update: Garlic. The Clinical Advisor, 9(8), 118121. Sego, S. (2006b). Alternative meds update: Saw palmetto. The Clinical Advisor, 9(5), 113-114. Sego, S. (2006o). Alternative meds update: St. John's wort. The Clinical Advisor. 9(7), 134-137. Sego, S. (2006d). What clinicians should know about herbals. The Ciinicai Advisor. 9(1), 46-51. Shan, Y. (2005)- Clinical aspects of herb-drug interactions. Primary i-ieaith Care. 15(7), 18-20. Spencer, J. (2004). The risks of mixing drugs and herbs. Wail Street Journal - Eastern Edition, pp. D1-D4. Tirona, R.G., & Bailey, D.G. (2006). Herbal product drug interactions mediated by induction. British Journai of Clinical Pharmacology, 61(6), 677-681. Tomiinson, B. (2006). Herb-drug interactions. Asia Pacific Biotech News, 10(5). 266268. Zhou, S. (2006). Herbal medicine and drug interactions. Innovation. 6(2), 44-45.

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