Warfarin (drug interactions)

• INTERACTIONS: Alfalfa, bromelain, chamomile, chondroitin, coenzyme Q₁₀, cranberry, danshen, devil’s claw, dong quai, feverfew, garlic, ginger, ginkgo, ginseng, green tea, ipriflavone, papain, PC-SPES, policosanol, Reishi, royal jelly, St. John’s wort, soy, vinpocetine, vitamin A, vitamin C, vitamin E, vitamin K, white willow

• TRADE NAME: Coumadin, Jantoven
• RELATED DRUGS: Anisindione (Miradon), dicumarol, Eliquis (apixaban), Xarelto (rivaroxaban), and Pradaxa (dabigatran)

DEFINITION: An anticoagulant used to thin the blood and prevent it from clotting.

Alfalfa

Effect: Possible harmful interaction

The herb alfalfa (Medicago sativa) is promoted for a variety of conditions. The relatively high vitamin K content in alfalfa could reduce the effectiveness of warfarin. Vitamin K directly counteracts warfarin’s blood-thinning effects. Since the amount of vitamin K in alfalfa varies widely, it is difficult to give an exact safe upper dose. As a precaution, avoid alfalfa supplements during warfarin therapy except under medical supervision.

Chamomile

Effect: Possible harmful interaction

The herb chamomile contains substances in the coumarin family. Some coumarins have blood-thinning actions that could interact with warfarin. One case report exists of a person in whom it appears that the combined use of chamomile and warfarin led to internal bleeding.

Chondroitin

Effect: Possible harmful interaction

Based on chondroitin’s chemical similarity to the anticoagulant drug heparin, it has been suggested that chondroitin might have anticoagulant effects as well. There are no case reports of any problems relating to this, and studies suggest that chondroitin has, at most, a mild anticoagulant effect. Nonetheless, chondroitin should not be combined with warfarin except under physician supervision.

Coenzyme Q10 (CoQ10)

Effect: Possible harmful interaction

CoQ₁₀ is a vitamin-like substance that plays a fundamental role in the body’s energy production. This substance is somewhat similar in structure to vitamin K, and reportedly, it, too, can reduce the therapeutic effects of warfarin. In three case reports, CoQ₁₀ was found to interfere with warfarin’s blood-thinning effects. A double-blind study found no interaction between CoQ₁₀ and warfarin. However, in view of warfarin’s low margin of safety, one should consult a physician before combining CoQ₁₀ with warfarin.

Cranberry

Effect: Possible harmful interaction

Several case reports suggest that cranberry juice can increase warfarin’s action, causing dangerous and potentially fatal bleeding problems. However, formal studies have failed to find evidence of such an interaction. Nonetheless, one should be cautious, especially when taking cranberry juice in dosages higher than eight ounces daily.

Danshen

Effect: Possible harmful interaction

The herb danshen, the root of Salvia miltiorrhiza, is used in traditional Chinese medicine to treat heart disease. Preliminary evidence, including several case reports, suggests that danshen can dangerously increase the effects of warfarin and cause significant bleeding problems. Persons taking warfarin should avoid danshen except under a physician’s supervision.

Devil’s Claw

Effect: Possible harmful interaction

The herb devil’s claw (Harpogophytum procumbens) is used for various types of arthritis and digestive problems. According to one case report, devil’s claw might increase the risk of abnormal bleeding when taken with warfarin. As a precaution, one should not combine devil’s claw and warfarin except under a physician’s supervision.

Dong Quai

Effect: Possible harmful interaction

The herb dong quai (Angelica sinensis) is used for menstrual disorders. According to one case report, dong quai may add to the blood-thinning effects of warfarin, thus increasing the risk of abnormal bleeding. One should avoid combining dong quai and warfarin without medical supervision.

Feverfew

Effect: Possible harmful interaction

The herb feverfew (Tanacetum parthenium) is primarily used for the prevention and treatment of migraine headaches. In vitro studies suggest that feverfew thins the blood by interfering with the ability of blood platelets to clump together. This raises the concern that feverfew might increase the risk of abnormal bleeding when combined with warfarin. However, there is little evidence that the blood-thinning effect of feverfew is significant in humans. Though an additive effect of feverfew and warfarin is uncommon, patients should avoid this combination except under medical supervision.

Garlic

Effect: Possible harmful interaction

The herb garlic (Allium sativum) is taken to lower cholesterol, among many other proposed uses. One of the possible side effects of garlic is an increased tendency to bleed. This blood-thinning effect has been demonstrated in a double-blind trial of garlic in sixty volunteers, as well as in other studies and one case report.

According to two other case reports, the blood-thinning effects of warfarin were greatly enhanced in persons taking garlic. This could amplify the risk of bleeding problems. Based on these findings, one should avoid combining garlic and warfarin except under a physician’s supervision.

Ginger

Effect: Possible harmful interaction

The herb ginger (Zingiber officinale) is used for nausea associated with motion sickness, morning sickness in pregnancy, and the postsurgical period. Ginger appears to thin the blood by interfering with the ability of blood platelets to clump together. As with feverfew, this raises the concern that ginger might increase the risk of abnormal bleeding when taken with warfarin. However, there is no evidence at present that the blood-thinning effect of ginger is significant in humans.

Though an additive effect of ginger and warfarin is rare, it is best to avoid this combination except under medical supervision. Ginger-flavored drinks should not present a problem, but candies containing whole dried ginger are potentially of concern.

Ginkgo

Effect: Possible harmful interaction

The herb ginkgo (Ginkgo biloba) has been used to treat Alzheimer’s disease and ordinary age-related memory loss, among many other uses. Inconsistent evidence suggests that ginkgo might reduce the ability of platelets (blood-clotting cells) to stick together. In addition, several case reports suggest that the use of ginkgo may be associated with an increased risk of serious abnormal bleeding episodes in persons taking the herb. These findings raise concern that ginkgo might add to the blood-thinning effects of warfarin, and there is one report of abnormal bleeding in an individual who had been taking the herb and drug together. However, two double-blind studies found no interaction between ginkgo and warfarin. These findings are reassuring. Nonetheless, warfarin has a low margin of safety, and one should consult a physician before combining ginkgo with warfarin.

Ginseng

Effect: Possible harmful interaction

Korean ginseng (Panax ginseng) is promoted as an adaptogen, a treatment that is said to help the body adapt to stress of all types. A case report suggests that P. ginseng can reduce the anticoagulant effects of warfarin. However, three double-blind studies failed to find any interaction. In general, double-blind studies are far more reliable than case reports, so these findings carry less weight. However, another double-blind trial that evaluated the closely related American ginseng species (P. quinquefolius) found that the use of the herb reduced the anticoagulant effects of warfarin, similar to what was seen in the case report. These combined findings suggest that caution should be exercised when combining ginseng and warfarin.

Low-Carbohydrate, High-Protein Diet

Effect: Possible harmful interaction

Low-carbohydrate, high-protein diets have been advocated for weight loss. However, several case reports indicate that adopting such diets may decrease the effectiveness of warfarin by increasing the blood levels of a serum called albumin. If warfarin binds to the albumin, it becomes less active in thinning the blood.

Green Tea

Effect: Possible harmful interaction

Dried green tea leaves contain significant levels of vitamin K on a per-weight basis. On this basis, people using blood thinners in the warfarin family should avoid green tea. However, green tea taken as a beverage provides such small amounts of the vitamin that the risk seems minimal for normal consumption. In one case report, problems developed in a person taking warfarin who consumed as much as a gallon of green tea daily.

Ipriflavone

Effect: Possible harmful interaction

Ipriflavone, a synthetic isoflavone that slows bone breakdown, is used to treat osteoporosis. Warfarin use increases the risk of osteoporosis. Because ipriflavone has been found to help prevent osteoporosis in certain circumstances, one might be tempted to consider taking this supplement while also using warfarin. However, some evidence indicates that ipriflavone might interfere with the body’s normal breakdown of warfarin. This could raise the levels of warfarin in the body and could increase the risk of abnormal bleeding.

Papain, Bromelain

Effect: Possible harmful interaction

One case report suggests that papain, a digestive enzyme found in papaya extract (Carica papaya), might add to warfarin's blood-thinning effect.

Vinpocetine

Effect: Possible harmful interaction

The substance vinpocetine is sold as a dietary supplement for the treatment of age-related memory loss and impaired mental function. Vinpocetine is thought to inhibit blood platelets from forming clots. For this reason, it should not be combined with medications or natural substances that impair the blood’s ability to clot normally, as this may lead to excessive bleeding. One study found only a minimal interaction between the blood-thinning drug warfarin and vinpocetine (and it actually involved an increased tendency for blood clotting), so one should use caution.

PC-SPES

Effect: Possible harmful interaction

PC-SPES is a patented herbal combination of eight herbs, including baikal skullcap, chrysanthemum flowers, reishi mushroom, licorice, ginseng, saw palmetto, and more that has shown promise for the treatment of prostate cancer. One case report suggests that PC-SPES might increase the risk of bleeding complications if combined with blood-thinning medications. Subsequent evidence has indicated that PC-SPES actually contains warfarin, making this interaction inevitable.

Policosanol

Effect: Possible harmful interaction

Policosanol, derived from sugarcane, is used to reduce cholesterol levels. It also interferes with platelet clumping, creating a risk of interactions with blood-thinning drugs.

For example, a thirty-day, double-blind, placebo-controlled trial of twenty-seven persons with high cholesterol levels found that policosanol at ten milligrams (mg) a day markedly reduced the ability of blood platelets to clump together. Another double-blind, placebo-controlled study of thirty-seven healthy volunteers found evidence that the blood-thinning effect of policosanol increased as the dose was increased: the larger the policosanol dose, the greater the effect. Another double-blind, placebo-controlled study of forty-three healthy volunteers compared the effects of policosanol (20 mg daily), the blood-thinner aspirin (100 mg daily), and policosanol and aspirin combined at these same doses. The results again showed that policosanol substantially reduced the ability of blood platelets to stick together and that the combined therapy exhibited additive effects. Based on these findings, persons should not combine warfarin and policosanol except under medical supervision.

Reishi

Effect: Possible harmful interaction

Some research suggests that reishi impairs platelet clumping. This creates the potential for an interaction with any blood-thinning medication and increases the risk of bleeding.

Royal Jelly

Effect: Possible harmful interaction

One case report indicates that use of royal jelly can increase the effectiveness of warfarin, creating risk of bleeding.

Soy

Effect: Possible harmful interaction

A small body of research indicates consuming soy products can decrease warfarin’s effectiveness by changing the body’s international normalized ratio (INR). Over time, soy changes the way blood clots, and the dose of warfarin may become too low to thin the blood properly. Though rare, individuals taking this medication should avoid ingesting large amounts of soy.

St. John’s Wort

Effect: Possible harmful interaction

The herb St. John’s wort (Hypericum perforatum) is primarily used to treat mild to moderate depression. Evidence suggests that St. John’s wort may interfere with warfarin, possibly requiring an increased dosage of the drug to maintain the proper therapeutic effect. Seven cases have been reported in which the blood-thinning effects of warfarin have been impaired in persons taking St. John’s wort. A hidden risk lies in this type of interaction. If taking warfarin, one should avoid St. John’s wort except under a physician’s supervision.

Vitamin A

Effect: Possible harmful interaction

Supplemental vitamin A might increase the blood-thinning effects of warfarin, and this could lead to an increased risk of abnormal bleeding. For this reason, it may be best to avoid combining vitamin A with warfarin unless supervised by a physician.

Vitamin C

Effect: Possible harmful interaction

Vitamin C taken in high dosages (more than 1,000 mg daily) has been reported to reduce the blood-thinning effect of warfarin. In one case, the person was taking 1,000 mg of vitamin C daily; another involved megadoses (about 16,000 mg daily). As a precaution, if taking warfarin, one should consult with a physician before taking high-dose vitamin C supplements.

Vitamin E

Effect: Possible harmful interaction

Because vitamin E thins the blood, it has been suggested that vitamin E should not be combined with warfarin. However, a four-week, double-blind study of twenty-five persons taking warfarin found no additive effect. None of the participants taking vitamin E at a daily dose of 800 or 1,200 IU showed an increased risk for abnormal bleeding.

In contrast, a case report indicated that vitamin E (800 IU daily) added to the effects of warfarin and resulted in abnormal bleeding. Because this effect did not become apparent until the fourth week, it is possible that problems might take longer to develop than the four weeks covered by the double-blind study or that certain persons might be more prone to an interaction. An unpublished, thirty-day study of three volunteers taking a warfarin-like drug also found an additive effect with only 42 IU of vitamin E daily.

Though only minimal evidence supports a possible interaction, it is best not to risk serious bleeding problems. One should avoid combining vitamin E with warfarin except under the supervision of a physician.

Vitamin K

Effect: Possible harmful interaction

Vitamin K is an antidote to warfarin that directly counteracts its blood-thinning effects. This is true for both supplemental vitamin K and foods high in vitamin K. Eating more vitamin K-rich vegetables can decrease warfarin’s therapeutic effect, and eating less can increase the drug’s effect. Either situation can lead to potentially life-threatening complications. Therefore, once established on a certain dose of warfarin, one should not change one’s usual vitamin K intake without consulting a physician. Foods to avoid or introduce into one's diet in moderation include asparagus, cauliflower, kale, lettuce, chickpeas, avocados, olive oil, liver, and aged cheeses. Pood products like Slim Fast shakes, Boost meal supplements, and some multivitamins may contain extra vitamin K and should be eaten cautiously.

One study suggests a novel way of deliberately using this effect. Researchers gave people on warfarin a fixed daily dose of vitamin K to override the changes in warfarin action caused by the natural variation in day-to-day dietary vitamin K consumption. The results were positive, as INR valuesthe standard measurement of warfarin’s blood-thinning effectbecame more stable. However, this method should not be used except under close physician supervision.

White Willow

Effect: Possible harmful interaction

The herb white willow (Salix alba), also known as willow bark, is used to treat pain and fever. White willow contains a substance that is converted by the body into a salicylate similar to the blood-thinner aspirin. Because white willow, like aspirin, may enhance the blood-thinning effects of warfarin, this combination should be avoided unless medically supervised.

Other Herbs and Supplements

Effect: Possible harmful interaction

One case report suggests that a combination of the herbs boldo and fenugreek increased the effects of warfarin. Another isolated case report suggests that the same can happen when fish oil is combined with warfarin. Other interactions may occur with alcohol and black licorice.

Based on their known effects or the effects of their constituents, the following herbs and supplements might not be safe to combine with warfarin, though this has not been proven:

• chamomile (Matricaria recutita)
• Coleus forskohlii
• ginger (Zingiber officinale)
• horse chestnut (Aesculus hippocastanum)
• papaya (Carica papaya)
• red clover (Trifolium pratense)
• reishi (Ganoderma lucidum)
• mesoglycan
• fish oil
• oligomeric proanthocyanidins (OPCs)
• phosphatidylserine

Bibliography

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