The consultant pharmacist - november 2006

Case Study in Geriatric
Pharmacotherapy
Herbal Product Use in a
Patient with Polypharmacy
Case Presentation
The patient is a 70-year-old black male who was being
seen in his home by a “house calls” nurse practitioner and a pharmacist for a routine visit. The house calls pro-gram is based at a large, academic medical center andserves more than 200 mostly geriatric patients who areindigent and homebound. The pharmacist and nurse A 70-year-old homebound patient was experiencing new- practitioner work as part of a multidisciplinary team that onset orthostatic hypotension and lightheadedness. The sees patients in their homes. The patient qualifies to par- pharmacist conducted a thorough medication review, ticipate in this program because he is homebound as a which revealed the use of several herbal products, includ- result of decreased mobility from severe osteoarthritis, ing St. John’s wort, in addition to several prescription he lives within a 15-mile radius of the medical center, medications. The pharmacist counseled the patient on the potential hazards of using herbal products with prescription The chief complaint at this visit was lightheadedness, medications. This prompted the patient to discontinue al which was present upon waking for the last several days, herbal supplements with the subsequent resolution of his and his worsening hip pain. The evaluation revealed that lightheadedness and orthostasis. He also experienced the patient had orthostatic hypotension. His blood pres- improvement in his pain control. Pharmacists need to be sure was 116/64 mm Hg lying down, 98/64 mm Hg vigilant in establishing a dialogue with their patients about sitting, and 90/64 mm Hg standing. His pulse was 84 the pros and cons of herbal product use, particularly with lying down, 80 sitting, and 96 standing. Blood pressure readings on the previous two visits (three and six months prior) were 106/64 mm Hg and 120/64 mm Key Words: Herbal products, Herbals, Herbal
Hg, respectively, with pulse rates in the 80s and no supplements, Herb-drug interactions, Polypharmacy.
Basic metabolic panel and blood chemistries were within normal limits, except for his hemoglobin (Hgb)and hematocrit (Hct), which were slightly low at 11.9g/dL and 34.6%, respectively. However, these were hisbaseline levels over the last couple of years. The patientdid not appear dehydrated (per exam nor per laboratoryvalues). He denied having any falls. His past medical history includes hypertension, chronic heart failure Kimberly A. Cappuzzo, PharmD, MS, CGP, is Assistant Professor of
Pharmacy, Geriatric Pharmacotherapy Program, Virginia Commonwealth
University School of Pharmacy, Richmond, Virginia.
For Correspondence: Kimberly A. Cappuzzo, PharmD, MS, CGP, PO
Box 980533, Virginia Commonwealth University School of Pharmacy,
Richmond, VA 23298-0533; Phone: 804-828-3252; Fax: 804 828-8359;
E-mail: [email protected].
Acknowledgement: The author thanks Jacklyn Ferrell, PharmD, for her
help with this manuscript. At the time of this writing she was a pharmacy
student at Virginia Commonwealth University School of Pharmacy.
2006, American Society of Consultant Pharmacists, Inc. All rights reserved.
VOL. 21. NO. 11 NOVEMBER 2006 THE CONSULTANT PHARMACIST Case Study: Herbal Product Use in a Patient with Polypharmacy
(ejection fraction = 20%), pain due to osteoarthritis, St. John’s wort 300 mg (1 tablet) by mouth twice neuropathy, depression, anxiety, benign prostatic hyper- trophy (BPH), and a history of gastritis. He also has a Bilberry 150 mg by mouth three times a day history of transient ischemic attacks and bilateral hip “Zing” 950 mg (2 capsules) by mouth daily replacements. The patient did remark that his hip pain Hawthorne extract 200 mg (2 capsules) by mouth seemed to be getting worse recently. He is blind in his right eye as a result of iritis and has glaucoma and CoQ10 (coenzyme Q-10) 10 mg (1 tablet) by mouth cataracts in his left eye; surgery is planned to take place “Cata-clear” (3 capsules) by mouth daily He denied any alcohol, tobacco, or illicit drug use. The “Colon-Helper” 900 mg (2 capsules) by mouth daily. patient was cachetic, but well groomed. He was neatly Some of these supplements are combination products.
dressed, in no acute distress, conversant, and pleasant, “Zing” contains bee pollen (105 mg), ginkgo biloba and stated his overall mood was okay, but with feelings of (158 mg), ginseng (212 mg), gota kola/gotu kola depression. The patient lives alone in a small apartment.
(158 mg), ho shou wu/fo-ti (53 mg), kola nuts (158 He has no immediate family, only a cousin who lives out mg), rehmannia (53 mg), and spirulina (53 mg).
of state. An aide provides assistance with meal prepara- “Cata-clear” contains bilberry (175 mg), glutathione tion, bathing, and other household chores for about four (5 mg), L-cysteine (100 mg), vitamin A (5,000 IU), hours each weekday. His review of systems was unre- riboflavin (10 mg), ascorbic acid (500 mg), vitamin E markable with the exception of lightheadedness, poor vision in the left eye, blindness in the right eye, and hip “Colon-helper” is a combination of aloe (290 mg), blue joint pain, rated at about five on a scale of 1 to 10. He vervain (72 mg), gentian (72 mg), goldenseal (30 mg), denied orthopnea, and showed no signs of bleeding. He slippery elm (290 mg), and white oak bark (146 mg).
expressed interest in seeing a psychiatrist for his depres- Additionally, he had taken valerian 100 mg by mouth daily and saw palmetto 80 mg by mouth daily.
At the time of the most recent visit, the patient’s prescribed medications included enteric-coated aspirin Pharmacist’s Assessment
81 mg by mouth daily, methadone 10 mg by mouth Extensive herbal supplement use along with the patient’s every morning and 5 mg every evening, enalapril 20 mg multiple prescription medications posed some potentially by mouth daily, furosemide 40 mg by mouth daily, panto- serious problems given the patient’s age, multiple prazole 20 mg by mouth daily, doxazosin 2 mg every comorbidities, and economic status. There was a high night at bedtime, and travoprost eye drops 0.004% one potential for interactions of the herbal supplements with drop in each eye daily. He also was taking sertraline 25 mg by mouth daily for about a month prior to the His lightheadedness and orthostatic hypotension may visit. He has had documented reactions of pruritus be secondary to his polypharmacy in conjunction with to codeine, nausea to meperidine, and an unknown the herbal supplements. His symptoms did not appear to be a result solely of his prescription medications since The pharmacist on the team spoke to the patient about all of them, except sertraline, had been started at least his prescription medications and enquired about the use two years prior to his complaints. More specifically, he of nonprescription and herbal medications. In this con- had received doxazosin 2 mg for the past two years and versation, the patient mentioned that he had read in furosemide 40 mg for four years without symptoms or Prevention magazine about herbal medications that could complaints. In fact, according to the patient, his symp- help many of his conditions and would improve his toms seemed to begin within a few days of starting the overall quality of life. Upon further questioning, the herbal products, approximately two to three weeks pharmacist found that he was taking a number of these supplements that he obtained from HCBL.com (Health There were several interactions identified between his Centers for Better Living). Among them were: herbal supplements and prescription medications that THE CONSULTANT PHARMACIST NOVEMBER 2006 VOL. 21. NO. 11 Case Study: Herbal Product Use in a Patient with Polypharmacy
could be considered potentially severe or even life- more energy and alertness. He admitted to no improve- threatening. St. John’s wort may potentially interact with ment in energy or mental alertness since starting the methadone and sertraline.1-3 The actions of methadone herbal products a few weeks ago. Furthermore, the may be decreased by increasing cytochrome P450 3A4 efficacy of both ginkgo and ginseng for chronic health (CYP3A4) metabolism of methadone or by activating P- conditions experienced by this patient is questionable.2 glycoprotein-mediated transport, thereby increasing the The safety and efficacy of the numerous other ingredi- elimination of methadone.1-3 Both of these alterations ents listed in each of the combination products the could impair the patient’s pain control, causing unneces- patient was taking are unknown. Hence, there may be other interactions and/or side effects not yet established A decrease in methadone plasma concentrations may lead to withdrawal symptoms, as has been found in Based on the available data and literature reports, former heroin addicts,3 but was not the case with our the exact cause of his lightheadedness and orthostatic patient. It is important to note that enzyme induction hypotension cannot be fully elucidated. However, consid- may persist for up to 14 days after St. John’s wort is ering the temporal association of the onset and disap- discontinued.4 There also may be additive serotonin- pearance of symptoms and the starting and stopping of reuptake activity with selective serotonin-reuptake the herbal products, the symptoms appear to be related inhibitors, such as sertraline, potentially leading to sero- tonin syndrome, particularly in elderly patients.1-3 Cost of the herbal supplements must be considered as Serotonin syndrome may involve hypertension, hyper- well. For less than a 30-day supply, these supplements thermia, gastrointestinal upset, mental status changes, cost approximately $86.99 (not including shipping and headache, myalgias, and motor restlessness. This syn- handling costs)9 and increased the patient’s pill burden drome can be fatal, especially in the elderly.3 Even though St. John’s wort appears to be effective for mild- Optimizing the patient’s prescribed antidepressant to-moderate depression,2 the risks of its use in this therapy may help better manage his depressive symp- patient clearly outweigh the benefits. Its use should be toms. An increase in the patient’s sertraline was suggest- minimized in patients receiving other medications, ed since he had already been taking 25 mg a day for Ginkgo biloba may possibly interfere with the actions of aspirin.6,7 Although the exact mechanism is unknown, Pharmacist’s Intervention
it is thought that ginkgo biloba acts by inhibiting platelet- After discussing with the patient the risks involved with activating factor and cyclic GMP phosphodiesterase,4,7 using herbal medications, particularly while concomi- which, in turn, inhibit platelet aggregation, causing an tantly using prescription medications, the patient agreed increased risk of bleeding when ginkgo and aspirin are to stop taking the herbal supplements. With the cessation taken together. The use of ginkgo with aspirin and other of St. John’s wort, our patient may be at risk for devel- antiplatelet agents or anticoagulants is a relative con- oping a withdrawal syndrome much like that observed traindication because of the increased risk of bleeding.6,7 with conventional antidepressants.4,10 Hence, the St.
Ginkgo also may cause an increased risk of postoperative John’s wort dose was tapered, decreasing to one tablet a bleeding, and this patient was scheduled for eye surgery day (from two times per day) for one week followed by about two weeks after the visit. Moreover, dizziness has discontinuation. The tapering sequence was empirically been reported with the use of ginkgo, and, theoretically, derived by the pharmacist. The patient continued all it may increase the patient’s risk of serotonin syndrome of his prescription medications as previously prescribed since ginkgo has been shown to have serotonergic activi- except for sertraline, which was increased to 50 mg by mouth every day after the St. John’s wort had been dis- Ginseng may decrease the diuretic effect of furosemide, continued. He also stopped taking his aspirin therapy for according to one case report.8 The patient was using the two weeks prior to his surgery, and we verified that “Zing,” which contains both gingko and ginseng, to gain he had restarted it after his surgery.
VOL. 21. NO. 11 NOVEMBER 2006 THE CONSULTANT PHARMACIST Case Study: Herbal Product Use in a Patient with Polypharmacy
The nurse practitioner and pharmacist saw him again prove that the product is unsafe before the agency can three weeks later, at which time he reported no light- take regulatory action, resulting in a postmarketing headedness. His blood pressure was 123/63 mm Hg lying regulatory system.16 Moreover, manufacturers of herbal down, 120/64 mm Hg sitting, and 121/64 mm Hg supplements are not required to have FDA approval or standing. His hypertension, heart failure, and vision status even to notify FDA before producing and marketing of were all stable, and his pain had improved (rated 1 to 2 on a 10-point scale). He stated that his overall mood was At this point, manufacturers of herbal products also good, despite baseline depression, and he was scheduled are not subject to good manufacturing practices enforced to begin seeing a psychiatrist within the next month. He by FDA for prescription and nonprescription medica- stated that, since the previous house calls visit, he had not tions.17,18 Therefore, there is no guarantee that herbal used any medication except for those prescribed, but he products meet standards for pharmaceutical quality.19 did enquire about using Viagra to reduce stress on his In other words, there is no guarantee that the product contains what is stated on the label. Herbal products may vary from batch to batch and from manufacturer to Discussion
manufacturer because of variations in preparations of Herbal product use has grown faster than any other the same herb. In fact, it is important to emphasize that “alternative” or “complementary” treatment modality,11 products from different manufacturers are different.
and use is continuing to rise rapidly, particularly among Furthermore, contamination, both with toxic ingredients aging baby boomers. Recent reports among nationally and with conventional drugs, is a real danger with herbal representative elderly subjects in the United States products and has been noted on several occasions.19,20 revealed 8% to 12.9% of elderly (≥ 65 years of age) have There is marked variability in the content and quality of used at least one herbal supplement in the preceding the marketed herbal supplements secondary to different year.12,13 Six percent of those seniors surveyed were tak- extraction and processing techniques used by the differ- ing both herbal and prescription drugs simultaneously in ent manufacturers; there also is variability in the concen- 1997-1998,12 and this figure jumped to 12.8% in 2002.13 trations and content of the constituent plant materials. However, more than 50% of herbal supplement users To answer this last criticism, several manufacturers did not discuss herbal product use with their doctor.12,13 have attempted to produce “standardized” herbal prod- At the same time, many health care providers do not ucts that contain a specific quantity of an active con- ask their patients about herbal product use.14,15 Making stituent. However, herbal products often contain more matters worse, there is a paucity of scientific research than 100 active ingredients,1 and there is no regulatory on herbal products and their use, so that those who wish system guaranteeing these products’ content and purity.
to obtain objective, factual information on the therapeu-tic benefit(s) or potential harm of herbal supplements Conclusion
would have to obtain information from books and pam- Our patient, like many other seniors, believed that phlets, most of which base their information on word- herbal products are perfectly safe since they are “natural of-mouth reputation, rather than relying on existing products” and not prescription drugs. Until further probing by the pharmacist, the patient’s health care Herbal products are regulated by the Food and Drug practitioners were not aware that he was even taking Administration (FDA) under different regulations than herbal supplements and that they could be causing or those governing prescription and nonprescription contributing to some adverse effects he was experienc- medications. Under the Dietary Supplement Health ing, such as lightheadedness and hypotension. They also and Education Act of 1994, manufacturers of herbal were unaware that there can be herb-drug interactions, and dietary supplements, unlike pharmaceutical manu- such as decreased pain control (St. John’s wort and facturers, are not required to provide evidence of safety or efficacy before marketing their products. Once an Herbal product use is widespread and continuing to grow, herbal supplement is marketed, the onus is on FDA to particularly among the elderly. Many patients are getting THE CONSULTANT PHARMACIST NOVEMBER 2006 VOL. 21. NO. 11 Case Study: Herbal Product Use in a Patient with Polypharmacy
their herbal supplement information from the lay press, and References
they are not discussing the use of these supplements with 1. Izzo AA. Herb-drug interactions: an overview of the clinical evidence.
Fundam Clin Pharmacol 2004;19:1-16.
their health care practitioners. As pharmacists and patient 2. Ernst E. The risk-benefit profile of commonly used herbal therapies: advocates it is important that we make a point of asking our ginkgo, St. John’s wort, ginseng, echinacea, saw palmetto, and kava. Ann patients about herbal product use and counseling them on the potential risks, especially with concomitant prescription 3. Izzo AA. Drug interactions with St. John’s wort (Hypericum perfora-tum): a review of the clinical evidence. Int J Clin Pharmacol Ther drug use. Moreover, the safety, efficacy, and quality of these products are often questionable because significant regulato- 4. Edie CF, Dewan N. Herbal hazards: which psychotropics interact with ry oversight of herbals is lacking. A number of herbal prod- four common supplements. Over-the-counter botanicals metabolized byCYP-450 enzymes pose a substantial interaction risk with antidepressants ucts, St. John’s wort in particular, have been linked to seri- and other drugs. Current Psychiatry Online 2005;4. Available at http:// ous herb-drug interactions. Much more research is needed www.currentpsychiatry.com/article_pages.asp?AID=846&UID=21105.
on herbal supplements before we can safely recommend Accessed December 19, 2005.
5. Desai AK, Grossberg GT. Herbals and botanicals in geriatric psychiatry.
Am J Geriatr Psychiatry 2003;11:498-506.
6. Kim YS, Pyo MK, Park KM et al. Antiplatelet and antithrombotic effects Key Points
of a combination of ticlopidine and ginkgo biloba extract (EGb 761).
Thromb Res 1998; 91:33-8.
Herbal product use is prevalent among elderly 7. Micromedex Healthcare Series online. Thomson Healthcare, Inc.
Available at: www.micromedex.com. Accessed March 15, 2006.
patients. Many are taking herbals concomitantly 8. Becker BN, Greene J, Evanson J et al. Ginseng-induced diuretic resis- with prescription and nonprescription medica- tions, with very limited knowledge of potential 9. Herbal supplement costs. Available at www.hcbl.com. Accessed January11, 2006.
adverse reactions and herb-drug interactions.
10. Dean AJ, Moses GM, Vernon JM. Suspected withdrawal syndrome after Patients often do not discuss herbal product use cessation of St. John’s wort. Ann Pharmacother 2003;37:150.
with their health care practitioners.
11. Eisenberg DM, Davis RB, Ettner SL et al. Trends in alternative medicine It is important as pharmacists and patient advo- use in the United States, 1990-1997: results of a follow-up national survey.
JAMA 1998;280:1569-75.
cates that we make a point of asking our patients 12. Foster DF, Phillips RS, Hamel MB et al. Alternative medicine use in about herbal product use and counsel them on the older Americans. J Am Geriatr Soc 2000;48:1560-5.
potential risks, especially with concomitant pre- 13. Bruno JJ, Ellis JJ. Herbal use among US elderly: 2002 National HealthInterview Survey. Ann Pharmacother 2005;39:643-8.
14. Yoon SL, Horne CH. Herbal products and conventional medicines usedby community-residing older women. J Adv Nurs 2001;33:51-9.
15. Sleath B, Rubin RH, Campbell W et al. Ethnicity and physician-older Additional Resources
patient communication about alternative therapies. J Altern Complement The following resources may be helpful for obtaining reliable, somewhat detailed herbal supplement informa- 16. DeAngelis CD, Fontanarosa PB. Drugs alias dietary supplements. JAMA2003;290:1519-20.
tion. A subscription fee is required for most of these 17. Holloman MS, Kuhn S. Special report: medication and dietary supple- except Entrez PubMed (individual articles may require ment safety, efficacy, and quality: a primer on appropriate product selec- tion. Washington, DC: American Pharmacists Association; 2004.
Entrez PubMed available at www.ncbi.nlm.nih.gov/ 18. Food and Drug Administration. FDA announces major initiatives fordietary supplements. Available at http://www.fda.gov/bbs/topics/news/ 2004/NEW01130.html. Accessed December 15, 2005.
Micromedex Healthcare Series online available at 19. Barnes J. Quality, efficacy, and safety of complementary medicines: fash- ions, facts and the future. Part II: efficacy and safety. Br J Clin Pharmacol2003;55:331-40.
Lexi-Comp (for online and PDA products) available 20. Ernst E. Risks of herbal medicinal products. Pharmacoepidemiol Drug Natural Medicines Comprehensive Database (for online, PDA, and hard copy products) available atwww.naturaldatabase.com. Clinical Pharmacology (for online and PDA products) available at www.clinicalpharmacology.com.
VOL. 21. NO. 11 NOVEMBER 2006 THE CONSULTANT PHARMACIST

Source: http://forwww.pcpcc.net/files/Cappuzzo_-_herbals.pdf