Complementary and alterative medicine (CAM) is defined as any product, including herbal remedies/foods/teas, vitamins, minerals, and natural products, that can be purchased without a prescription at a health food store, supermarket, from a magazine/newspaper or online, for self-treatment.1
Taylor et al. evaluated CAM perceptions of emergency department patients in Australia. They determined 44% of patients felt that by using CAM they were “drug free,” with 29% of patients agreeing (or strongly agreeing) CAM use is always safe to take with prescription medications. In an earlier study, Eisenberg et al. evaluated CAM use perceptions in the United States and found 79% of patients felt that, combined with prescription drugs, CAM was superior to either modality alone.2 They also found 63% to 72% of CAM-using patients that had seen a medical doctor in the prior year did not disclose the therapy.
The two most common reasons cited by patients were “they felt it wasn’t important for the doctor to know (61%)” and “the doctor didn’t ask (60%).” Overall, national CAM-use surveys have revealed that about 80% of adults typically do not disclose CAM use to medical doctors.
It is, therefore, imperative that physicians ask patients about their CAM use. It also is important to remember there are more foods and beverages that contain some of these “natural” ingredients, and patients need to be queried about the use of these products. CAM products can complicate traditional patient management, either when used alone or in combination with prescription drugs.
A clinically significant drug interaction that bears its own warning is that of warfarin and chondroitin/glucosamine. Patients might not tell you that they are taking chondroitin/glucosamine, so you have to ask. Functional foods and beverages that include “natural” ingredients, such as glucosamine and chondroitin, and other CAM abound. Examples include Joint Juice (1,500 mg glucosamine), Vitamin Water, and others.3
Two case reports, and a report from the World Health Organization (WHO) Collaborating Center for International Drug Monitoring, and the MedWatch database point to a potentially serious drug interaction between glucosamine and warfarin.4-7 Although not FDA approved for joint supplementation, the usual daily dose should generally not exceed 1.5 grams of glucosamine and 1.2 grams of chondroitin. Chondroitin may have anti-coagulant activity, which would explain the increase in International Normalized Ratio (INR) seen in patients using it in combination with warfarin. The WHO database identified at least 34 cases of concomitant use, with most cases of increased INR resolving upon glucosamine discontinuation. Nine cases required physician intervention, and in one case a positive rechallenge was documented. In June 2007, there were 81 cases of a possible interaction from the MedWatch database, of these, 61 cases had potential alternate etiologies. Of the 20 possibly-related cases, five led to patient hospitalization due to bleeding complications; the median patient age was 62 years and there were no deaths reported.
Ramsay et al. reported from a United Kingdom survey that 92% of patients admitted to taking herbal medicines while receiving warfarin, noting that significant numbers of patients are in need of close monitoring. They also note that other CAM can interact with warfarin to increase bleeding time or act as anti-platelet agents (e.g., high dose vitamin E [> 400 IU], fish oils, garlic, St. John’s Wort, etc.) They particularly note that all patients receiving warfarin or that will be commencing warfarin be specifically asked about their use of CAM. The mechanism for this interaction still is unclear, but may be due to the inhibition of warfarin metabolism by the CYP2C9 or CYP3A4 enzymes, or a pharmacodynamic interaction between glucosamine and warfarin.
It is critical all patients, particularly those taking warfarin, have a full drug history at all hospitalizations. Make sure you inquire about vitamins and other supplements/CAM. If someone else is doing the intake medication history, make sure they get this information. A nurse might not think to ask. TH
Michele B. Kaufman, PharmD, BSc, RPh, is a registered pharmacist based in New York City.
1. Taylor DM, Walsham N, Taylor SE, Wong LF. Complementary and alternative medicines versus prescription drugs: perceptions of emergency department patients. Emerg Med J. 2006;23:266-268.
2. Eisenberg DM, Kessler RC, Van Rompay MI, et al.. Perceptions about complementary therapies relative to conventional therapies among adults how use both: results from a national survey. Ann Intern Med. 2001;135:344-351.
3. What is Joint Juice? Joint Juice, Inc. www.jointjuice.com/jointjuice.php. Published 1997. Accessed August 1, 2008.
4. Rozenfeld V, Crain JL, Callahan AK. Possible augmentation of warfarin effect by glucosamine-chondroitin. Am J Health-Syst Pharm. 2004;61:306-307.
5. Knudsen JF, Sokol GH. Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: case report and review of the literature and medwatch database. Pharmacother. 2008;28(4):540-548.
6. Ramsay NA, Kenny MW, Davies G, Patel JP. Complimentary and alternative medicine use among patients starting warfarin. Br J Haematology. 2005;130:777-780.
7. Yue Q-Y, Strandell J, Myrberg O. Concomitant use of glucosamine may potentiate the effect of warfarin. The Uppsalla Monitoring Centre Web site. www.who-umc.org/graphics/9722.pdf; Accessed August 1, 2008.