warfarinfo

Warfarin Institute of America

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GINKGO BILOBA INTERACTIONS WITH WARFARIN

There are some reports of ginkgo causing bleeding when taken with warfarin. There are two groups of active ingredients in ginkgo, flavinoids and terpenoids. The flavinoids are ingredients by which ginkgo products are standardized. However, these are not the ingredients which are involved in causing bleeding. The terpenoids are not standardized and they are involved with bleeding. There is a report of the amount of terpenoids varying from 7% to 13% in different bottles of the same standardized brand. This would be a near doubling of the dose of the interacting ingredients.

Since the benefits of ginkgo have been shown to be slight, and there is a risk of bleeding, it would best to avoid this combination.

Also consider the following abstract

Some writers hold the view that the combination of Ginkgo biloba with anticoagulant or antiplatelet drugs represents a serious health risk. Such concerns are largely based on the assumption that Ginkgo has clinically relevant antiplatelet activity, as well as accounts of bleeding episodes associated with Ginkgo consumption. To investigate whether these bleeding episodes have a pharmacodynamic, idiosyncratic or coincidental basis, a review of controlled clinical studies and case reports was undertaken. Results from controlled studies consistently indicate that Ginkgo does not significantly impact haemostasis nor adversely affect the safety of coadministered aspirin or warfarin. Most of these studies were undertaken using EGb 761, a well-defined extract of Ginkgo biloba. In contrast, EGb 761 has not generally been implicated in the case reports. In general, the quality of these case reports is low. Nevertheless, the possibility of an idiosyncratic bleeding event due to Ginkgo use cannot be excluded on the basis of the available information. However, there is scant information from case reports or controlled trials to support the suggestion that Ginkgo potentiates the effects of anticoagulant or antiplatelet drugs. Such high-level safety concerns for this herb are deemed to be unsupported by the currently available evidence.

References:

Heck AM, DeWitt BA, Lukes AL. Potential Interactions Between Alternative Therapies and Warfarin. Am J Health-Syst Pharm. 2000; 57:1221-30

Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: What is the evidence? Mol Nutr Food Res. 2008;Jan 23 Epub Ahead of Print.

The following was written by one of my students

Ginkgo biloba is used to increase blood flow and skin perfusion, to decrease blood viscosity and erythrocyte aggregation.(¹⁾ Of interest, ginkgo contains two major constituents: flavonoids and terpenoids. Standardization normally occurs by flavonoids, but the terpenoids contain the PAF (PAF is required for platelet aggregation). (4,1) PAF inhibition occurs primarily by ginkgolide B. (2,3) Multiple case reports are found in the literature involving adverse reactions after taking ginkgo biloba.

Case reports:

70 year-old male with spontaneous bleeding into his eye after one week of BID ginkgo; also taking aspirin 325 mg daily for 3 years (5)

78 year-old male with intracerebral hemorrhage; also taking warfarin, stable for 5 years (6)

33 y-ear old female with bilateral subdural hematoma, took ginkgo for 2 years, no concurrent meds, stopped ginkgo with no recurrence (7)

72 year-old male with 7 mm left frontal subdural hematoma, no mention of any concurrent meds (9)

Studies:

Double-blind placebo controlled study in 6 healthy volunteers found PAF antagonism(⁸⁾

Of 55 trials reviewed, no drug interactions mentioned and side effects reported to be very low (1)

Bleeding has occurred in patients on no other medications, patients on concurrent aspirin, and patients on concurrent warfarin. This herb has a well documented risk of bleeding and should be avoided in patients taking warfarin.

Significance: Major (3)

References:

1: Kleijnen J, Knipschild P. Ginkgo biloba. Lancet 1992; 340: 1136-9.

2: Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998; 158: 2200-9.

3: http://www.micromedex.com Complementary and Alternative Medicine AltMedDex, as seen on March 1, 2001.

4: Smolinske SC. Dietary supplement-drug interactions. JAMWA 1999; 54: 191-5.

5: Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion on Ginkgo biloba extract. N Engl J Med 1997; 336:1108.

6: Matthews, MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998; 50: 1933-4.

7: Rowin J, Lewis SL. Spontaneous bilateral subdural hematomas associated with chronic Ginkgo biloba ingestion. Neurology 1996; 46:1775-6.

8: Chung KF, McCusjer M, Page CP, Dent G, Guinot PH, Barnes PJ. Effect of a ginkgolide mixture (BN 52063) in antagonising skin and platelet activating factor in man. Lancet 1987; 248-51.

9: Gilbert GJ. Ginkgo biloba. Neurology 1997; 48: 1137.

©2001 Patricia Chuong Used by Permission

Editor's Note: You have to be careful when evaluating all studies with ginkgo, because as mentioned in the first paragraph, there is variation from batch to batch even with the same product. Therefore, if a study used only one batch, it only means that there was not enough of the terpenoids in that batch to cause no harm. It cannot be inferred that there will not be enough terpenoids in another batch or brand to cause harm.

An editorial about the lack of concern for manufacturers of these products and their interactions with other medications.

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Last updated January 28, 2008