Herbal Medications—Not Harmless Anymore

Sources: Piscitelli SC, et al. 8th Conference on Retroviruses and Opportunistic Infections (CROI), Chicago, Ill, Feb. 4-8, 2001. Abstract #743; Southwell H, et al. 8th CROI, Chicago, Ill, Feb 4-8, 2001. Abstract #497.

In the first of these abstracts, 10 HIV-negative volunteers underwent pharmacokinetic studies to determine the potential interaction between garlic and saquinavir. In this study, the volunteers were given 1200 mg of saquinavir 3 times daily with meals for 3 days, and baseline levels were drawn on the morning of day 4. Garlic capsules of known allicin content were given twice daily with meals for days 5-25. Saquinavir was again added for days 22-24. At day 25, the AUC, Cmin, and Cmax levels of saquinavir were measured and determined to be approximately 50% of baseline levels. It was also noted that even after a 3-week washout, the 3-day saquinavir levels remained approximately 60-70% of baseline. Piscitelli and associates stated that garlic supplements may produce a prolonged induction of saquinavir metabolism.

In the second abstract, 324 patient interviews were conducted at the University of Cleveland from April to July 2000. The summary of these interviews showed that 267 (82%) confirmed using some type of alternative medication. In fact, more than 567 different forms of alternative therapies were catalogued during these interviews. Most patients (59%) stated they had informed their physician about their alternative therapy use, but it was found to be documented in the chart only 13% of the time. Patients were more likely to inform their physicians about their use of anabolic steroids or protein supplements than teas or alternative therapies.

Comment by Thomas G. Schleis, MS, RPh

In recent years, the sales of complementary and alternative medicines (CAMs) have skyrocketed. Once limited to health food stores, CAMs can now be found on the shelves of most pharmacies and grocery stores. The increase in sales of these products can be attributed to many different factors. The desire to achieve a healthier lifestyle, dissatisfaction with traditional medications and their side effects, and the desire for a potential cure when one does not exist in traditional medicine are just some of the reasons for this phenomenon. While some data support the clinical efficacy of some CAMs, much of their use is the result of anecdotal information.

For a number of years, the industry surrounding the sales and marketing of CAMs was under little regulation, in part because the products appeared to be safe. Unfortunately, while these preparations may individually be safe in many cases, a number of serious drug interactions have surfaced over the last 3-5 years as CAMs have become more commonly used. HIV medications and warfarin are pharmaceuticals that have exhibited potentially serious drug interactions with many of the herbal preparations (see Table 1).

Table 1: Drug Interactions of Herbal Preparations with HIV Medications, Antifungals, and Warfarin
Drug Herbal Preparation Interaction Reference

Garlic Saquinavir* Dec saquinivir levels 1. Piscitelli SC, et al.
Warfarin and other drugs with antiplatelet activity Inc effect of warfarin Theorized
 
Ginkgo biloba Warfarin and other drugs with antiplatelet activity Inc effect of warfarin Theorized with warfarin, documented with aspirin (2)
 
Ginseng Warfarin Inc effect of warfarin 3. Janetzky K, Morreale AP.
 
Milk Thistle Saquinavir* Dec saquinavir levels 4. Study ongoing at this time.
 
St. John’s wort Indinavir* Dec indinavir levels 5. Piscitelli SC, et al.
Warfarin Dec effect of warfarin 6. Yue QY, et al.
Azole antifungals Dec antifungal activity Theorized
 
*Could potentially interact with all antiretroviral protease inhibitors such as amprenavir, indinavir, nelfinavir, ritonavir, and saquinavir as well as non-nucleoside reverse transcriptase inhibitors such as delavirdine, efavirenz, and nevirapine.

Unfortunately, patients with HIV or cancer are often individuals who are looking for alternative therapies to supplement their traditional therapy—especially when the long-term prognosis is not good.

In Piscitelli et al’s abstract, the interaction between garlic and saquinavir was studied. Garlic capsules are commonly taken by the lay public to slow the process of atherosclerosis and to control hypertension. Garlic administration has been shown to reduce blood sugar levels, cholesterol, triglycerides and LDL, increase HDL, reduce platelet adhesiveness, and increase fibrinolytic activity. It is also touted as a means to ward off coughs and colds although scientific confirmation of this is lacking. The interaction between garlic and saquinavir was significant in healthy individuals, although what the effect in HIV-infected patients would be cannot be directly extrapolated since HIV-infected patients exhibit AUC and Cmax levels about twice those in healthy, non-HIV-infected individuals. It would have also been interesting to have sampled some patients who did not receive garlic at all, to see if their baseline levels were identical to their levels when challenged several weeks later. It would also have been helpful to compare the amount of allicin in capsules vs. that contained in prepared foods to determine the relative risk of garlic obtained in the diet. Nonetheless, an interaction of the magnitude seen in this study is cause for alarm.

Complicating the effective monitoring of drug interactions between CAMs and pharmaceuticals is that many patients do not consider CAMs to be "drugs," or do not divulge the use of these preparations to their physician or health care professional for fear of ridicule. Even if patients do divulge this information, it is seldom documented in the patient’s medical record, as evidenced in the second abstract. This may be the result of health care professionals not seeing the value of recording all medications that a patient is taking. I would argue that it is necessary to document all of the medications that a patient is taking, be it of pharmaceutical or natural origin. All health care professionals need to become more familiar with herbal preparations, their potential side effects, and drug interactions. Fortunately, there are a number of resources available that are updated on a regular basis to keep abreast of the current literature. (See Table 2.) It would be worthwhile for every medical practice to have at least one of these references available.

Table 2: Alternative Medicine References
Reference Source

www.naturaldatabase.com Worldwide web

Journal of Alternative and Complementary Medicine Mary Ann Liebert, Inc., 2 Madison Avenue, Larchmont, NY 10538. 914-834-3100. www.liebertpub.com

The Review of Natural Products Facts and Comparisons 111 West Port Plaza, Suite 300, St. Louis, MO 63146. 800-223-0554.

Clinical Pharmacology Gold Standard Multimedia 320 West Kennedy Blvd., Suite 400, Tampa, FL 33606. (813) 258-4747. www.gsm.com

Dr. Schleis is Director of Pharmacy Services, Infections Limited, Tacoma, Wash.

References

1. Piscitelli SC, et al. 8th CROI, Chicago, Ill, Feb 4-8, 2001. Abstract #743.

2. Rosenblatt M, Mindel J. N Engl J Med. 1997;336:1108.

3. Janetzky K, Morreale AP. Am J Health Syst Pharm. 1997;54:692-693.

4. Study ongoing at this time. Personal communication.

5. Piscitelli SC, et al. Lancet. 2000;355:547-548.

6. Yue QY, et al. Lancet. 2000;355:575.