Potential Interactions - Alternative Therapies and Warfarin

Potential Interactions of Herbs with Warfarin

Several herbs may have the potential to interfere with warfarin therapy. However, because information about the pharmacologic activity, therapeutic efficacy, and adverse effects of most alternative medicine products is limited, the clinical significance of potential warfarin-herb interactions is unknown. Herbs that have been identified as having the theoretical potential to interfere with warfarin therapy are listed in this Table . ^{[5,6,7,8,9,10,11]} Further study is needed to confirm these potential interactions and assess their clinical significance.

Herbs with Coumarin, Salicylate, or Antiplatelet Properties

Several natural products contain substances that have coumarin, salicylate, or antiplatelet properties. Therefore, a theoretical risk for potentiation of the pharmacologic activity of warfarin exists when these herbs are taken with warfarin. Herbs thought to contain coumarin or coumarin derivatives include angelica root, arnica flower, anise, asafoetida, celery, chamomile, fenugreek, horse chestnut, licorice root, lovage root, parsley, passionflower herb, quassia, red clover, and rue.^[5,6,7,8,9] Meadowsweet, poplar, and willow bark contain high concentrations of salicylates, while bromelain, clove, onion, and turmeric have been reported to exhibit antiplatelet activity.^[5,8] Borage seed oil contains glinoleic acid, which may increase coagulation time.^[10] Bogbean has been noted to demonstrate hemolytic activity,^[8] and capsicum has been reported to cause hypocoagulability. ^[11] There have been no documented case reports of an interaction of warfarin with any of these herbs. However, patients taking any products containing these herbs concurrently with medications that have anticoagulant effects, such as warfarin, should be closely monitored for signs or symptoms of bleeding.

Sweet clover also contains coumarin derivatives and therefore poses an increased risk of bleeding if given with warfarin.^[5] There have been no reports of an interaction between sweet clover and warfarin or hemorrhagic disease in humans. However, several cases of severe hemorrhage and death have been reported in cattle. ^[12,13] Patients taking both sweet clover and an anticoagulant should be monitored closely for signs and symptoms of bleeding, and the International Normalized Ratio (INR) should be closely monitored.

Feverfew

Feverfew (Tanacetum parthenium) is commonly used for the treatment of migraine headaches, arthritis, and various type of allergies. ^[5,14,15] This herb is thought to exert its pharmacologic activity by inhibiting serotonin release, histamine release, prostaglandin synthesis, and platelet release and aggregation.^[5,16] Several in vitro studies have shown feverfew to interfere with hemostasis and platelet aggregation by neutralizing platelet sulfhydryl groups, as well as preventing prostaglandin synthesis.^{[17,18,19,20]} Parthenolide, one of the many sesquiterpene lactone constituents of feverfew extract, has been shown to exert the greatest pharmacologic activity.^[20] However, a recent study found that most commercially available feverfew products do not contain substantial amounts of parthenolide. ^[21]

Although there are no documented reports of feverfew interacting with warfarin in humans, pharmacologic data suggest the potential for additive anticoagulant effects in the presence of warfarin. The clinical significance of this potential interaction has not been determined. Until more data are available, it is recommended that patients taking warfarin avoid products containing feverfew in order to prevent potentially serious bleeding.

Garlic

Garlic (Allium sativum) is thought to provide several cardiovascular benefits, such as blood pressure lowering, serum lipid lowering, and antithrombotic activity.^[6,14] Garlic oil has been reported to interrupt thromboxane synthesis, thereby inhibiting platelet function.^[22] One author reported that in vitro platelet aggregation decreased within five days when blood samples from six healthy adults were mixed with essential garlic oil.^[23] An elderly man developed a spontaneous epidural hematoma after he ingested approximately 2000 mg of garlic daily (equivalent to about four cloves) for an undetermined period.^[24] The man denied use of aspirin, nonsteroidal anti-inflammatory drugs, and any other medications that may precipitate a bleeding event.

There have been no reports of potentiation of warfarin's activity with concomitant administration of garlic, but the available information suggests that a serious interaction is possible. Patients taking warfarin should be advised to avoid garlic supplements. However, they should also be aware that regular ingestion of food products containing small amounts of garlic should not pose a problem. If excessive garlic consumption and warfarin use occur concomitantly, the patient's INR should be closely monitored.

Ginger

Ginger (Zingiber officinale), promoted for use in motion sickness and arthritis, has been reported to reduce platelet aggregation through the inhibition of thromboxane synthetase. ^[25] Ginger supplements, containing amounts of ginger much greater than regularly found in food products, may lead to an increased risk of bleeding when taken with warfarin. Therefore, patients taking warfarin and ginger supplements concurrently should have their INR checked regularly and be advised to watch for symptoms of bleeding.

Ginkgo

Ginkgo (Ginkgo biloba) is a common herbal product available in the United States and advertised to improve cognitive function.^[5,6,14] Ginkgolide B, one component of ginkgo, inhibits platelet-activating factor by displacing it from its receptor- binding site, resulting in reduced platelet aggregation.^[26] Several cases of bleeding thought to be secondary to ginkgo ingestion have been reported. ^[27,28,29] A 70-year-old man ingested 40 mg of concentrated ginkgo extract twice daily for one week. He complained of blurred vision and was diagnosed with a spontaneous hyphema. ^[27] He was also taking 325 mg of aspirin daily. A second report involved a 33-year-old woman who complained of diffuse headaches and was later diagnosed with bilateral subdural hematomas.^[28] The patient's medication list included occasional acetaminophen use, a brief trial of ergotamine- caffeine tablets, and 60 mg of ginkgo twice daily for two years. Yet another report described a 72- year-old woman diagnosed with a left frontal subdural hematoma after taking 50 mg of ginkgo three times daily for at least six months.^[29]

Currently, there are no reports of bleeding associated with concomitant administration of warfarin and ginkgo. However, it is recommended that patients taking warfarin, or any other anticoagulant, not take ginkgo-containing products because of an increase in the risk of serious bleeding.

Table Potential and Documented Interactions of Herbs with Warfarin
^a Excessive amounts are necessary for this interaction to occur.

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