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Herbal Medication: Potential for Adverse Interactions with Analgesic Drugs

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Herbal Medication: Potential for Adverse Interactions with Analgesic Drugs Journal of Clinical Pharmacy and Therapeutics (2002) 27, 391–401 REVIEW ARTICLE Herbal medication: potential for adverse interactions with analgesic drugs W. Abebe PhD Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, GA, USA of the potential adverse interactions between SUMMARY herbal supplements and analgesic drugs, and take The use of herbal supplements in the US has appropriate precautionary measures to avoid their increased dramatically in recent years. These possible occurrences. However, as most of the products are not regulated by the Food and Drug interaction information available is based on Administration (FDA) with the same scrutiny as individual case reports, animal studies and in vitro conventional drugs. Patients who use herbal data, further research is needed to confirm and supplements often do so in conjunction with assess the clinical significance of these potential conventional drugs. This article is a review of interactions. potential adverse interactions between some of the commonly used herbal supplements and Keywords: acetaminophen, adverse drug inter- analgesic drugs. Non-steroidal anti-inflammatory actions, analgesic drugs, herbal supplements, drugs (NSAIDs), particularly aspirin, have the NSAIDs, opioids potential to interact with herbal supplements that are known to possess antiplatelet activity (ginkgo, garlic, ginger, bilberry, dong quai, INTRODUCTION feverfew, ginseng, turmeric, meadowsweet and willow), with those containing coumarin (cham- The use of herbal supplements in the US has omile, motherworth, horse chestnut, fenugreek become increasingly popular in recent years. In a and red clover) and with tamarind, enhancing the survey conducted in 1999, about 49% of adult risk of bleeding. Acetaminophen may also inter- Americans were estimated to have used herbal act with ginkgo and possibly with at least some of products during the previous year (1). Of these, the above herbs to increase the risk of bleeding. about 24% had used these products on a regular Further, the incidences of hepatotoxicity and basis. These medications fall into the category of nephrotoxicity may be augmented by acetamino- alternative ⁄ complementary medicines and, as such, phen when concomitantly used with the poten- are not regulated by the Food and Drug Admin- tially hepatotoxic herbs Echinacea and kava, istration (FDA) with the same scrutiny as conven- and with herbs containing salicylate (willow, tional drugs. Their regulation by the FDA is meadowsweet), respectively. The concomitant use restricted as a result of the Dietary Supplement of opioid analgesics with the sedative herbal Health and Education Act (DSHEA) passed by supplements, valerian, kava and chamomile, may US Congress in 1994. These products are avail- lead to increased central nervous system (CNS) able to consumers as over-the-counter (OTC) depression. The analgesic effect of opioids may items in various forms of preparations or dos- also be inhibited by ginseng. It is suggested that ages. Several factors are believed to contribute to health-care professionals should be more aware the increasing trend of herbal supplement util- ization in this country: ease of accessibility, the Received 1 August 2001, Accepted 14 October 2002 desire for self-medication, and the perceptions Correspondence: Worku Abebe PhD, Department of Oral Bio- logy and Maxillofacial Pathology, School of Dentistry, CB 3710, that herbs are safer, gentler and less costlier Medical College of Georgia, Augusta, GA 30912–1128, USA. Tel.: than conventional drugs, among others. These 706 721 3181; fax: 706 721 6252; e-mail: [email protected] and related aspects of utilization of herbal Ó 2002 Blackwell Science Ltd 391 392 W. Abebe supplements have been reviewed in some details ketorolac, ketoprofen, meclofenamide and etdolac; recently (2–4). (ii) acetaminophen and (iii) the opioids, codeine, As the use of herbal supplements in the US oxycodone, dihydrocodeine, morphine, hydro- continues to grow under the prevailing scenario, morphone, oxymorphone, methadone, fentanyl, some concerns have become apparent regarding suphentanyl, alfentanil, levorphanol, meperidine, the safety of these products. Of particular safety pentazocine, nalbuphine, buprenorphine, butor- concern is potential interactions of these products phanol, hydrocodone, dihydrocodeine and pro- with conventional drugs. It has been documented poxyphene (6–8). The widespread use of analgesics, that as many as 31% of the patients who use herbal both as OTC and prescription items, demands that supplements do so in conjunction with prescribed health-care professionals should be aware of their drugs and about 70% of these patients do not possible interactions with herbal supplements. regularly report the use of these products to their Such information has not yet been compiled health care providers (1). Another study also systematically and this brief review is the first demonstrated that about 26% of presurgical pa- attempt towards that goal. For the purpose of this tients who utilize herbal supplements take OTC review, the analgesics are classified as described drugs concurrently (5). In view of the ongoing above and their possible interactions with herbal trend, it is likely that health-care professionals will supplements are examined according to this encounter more often than before patients who use classification. herbal supplements and who may seek their help concerning herb–drug interactions. In order to POTENTIAL INTERACTIONS OF ASPIRIN appropriately tackle this problem and provide a AND NON-SALICYLATE NSAIDS WITH more adequate health-care service to such patients, HERBAL SUPPLEMENTS practitioners should be knowledgeable of at least the commonly occurring or anticipated interactions Aspirin and non-salicylate NSAIDs are commonly between herbal supplements and conventional used for the management of mild-to-moderate drugs. These interactions may be additive or sy- pain. These drugs reduce the synthesis of prosta- nergistic, whereby the herbal product increases or glandins and thromboxanes by inhibiting ⁄ inacti- potentiates the action of the drug. By contrast, the vating the cyclooxygenase enzyme (6, 7). While the herb may also be antagonistic to the action of the inhibitory effect of aspirin on cyclooxigenase is drug. While herb–drug interactions may involve irreversible, that of the non-salicylate NSAIDs is pharmacodynamic and pharmacokinetic mecha- reversible. Therefore, compared with the non- nisms, they may result in either beneficial or salicylate NSAIDs, aspirin has a greater potential adverse effects. for causing effects resulting from inhibition of In this paper, possible adverse interactions that cyclooxygenase. However, for both groups of may occur between some of the popular herbal drugs, interactions may occur with herbal supple- supplements in the US market and analgesic drugs ments whose actions involve the production of are reviewed briefly based on the available litera- prostaglandins and ⁄ or thromboxanes. In addition, ture information. Some of the information provi- both aspirin and the non-salicylate NSAIDs are ded is supported with documented data, whereas highly plasma protein-bound and this may further others have their basis on theoretical grounds. predispose them to possible interactions with herbs Along with this information, a brief description of that share this property, although such interactions the major therapeutic applications of each herb is have not yet been documented in the literature. provided. Aspirin, at relatively high doses (e.g., >3 g ⁄ day), Analgesics are one of the most frequently used also causes a reduction in prothrombin, a plasma drugs for medical as well as dental purposes in the factor involved in blood clotting (8). US. These drugs are available as OTC and ⁄ or pre- A survey of the literature indicates that a num- scription items. The commonly used analgesic ber of herbal supplements have antiplatelet and drugs include (i) aspirin and the non-salicylate anticoagulant (i.e., those containing coumarin de- non-steroidal anti-inflammatory drugs (NSAIDs), rivatives) properties, and tamarind can interact ibuprofen, flurbiprofen, diflunisal, naproxen, with aspirin and some of the other NSAIDs (9–16). Ó 2002 Blackwell Science Ltd, Journal of Clinical Pharmacy and Therapeutics, 27, 391–401 Herb–analgesic interactions 393 spontaneous bleeding in the eyes of a 70-year-old Interactions with antiplatelet herbs man who was given aspirin while taking ginkgo One of the consequences of thromboxane synthesis extracts (21, 22). Therefore, the concurrent admin- inhibition by aspirin and the non-salicylate istration of aspirin or other NSAIDs with ginkgo NSAIDs is a reduction in platelet aggregation. This may present an additional risk of bleeding. process interferes with clotting mechanisms, pro- Appropriate precautions are recommended for longing bleeding time. High doses of aspirin by avoiding such herb–drug interactions. reducing prothrombin production can also con- tribute to bleeding problems, as noted above. Garlic (Allium sativum). Garlic is one of the largest Moreover, NSAIDs, particularly aspirin, by inhib- selling and most extensively researched herbs. It is iting prostaglandin generation in the gastric popularly believed to provide several cardiovas- mucosa, eliminate cytoprotection with possible cular benefits including the lowering of blood damaging effects on the mucosa, leading to gastric pressure, prevention of age-related changes
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