Interactions with Ginkgo Biloba

Concurrent use of ginkgo with warfarin may increase the risk of bleeding (Fugh-Berman 2000). There is a case report of intracerebral hemorrhage in a 78-year-old woman who used ginkgo while on warfarin therapy (Matthews 1998). Another case report concerning a possible interaction between aspirin (325 mg/day) and ginkgo (40 mg) involved a 70-year-old man who developed spontaneous hyphema while taking both substances together (Rosenblatt and Mindel 1997). These interactions may be related to inhibition of PAF. In a rat study, the combination of ticlopidine (50 mg/kg/day) and ginkgo (40 mg/kg/day) administered orally prolonged bleeding times by 150% (Kim et al. 1998). Given these reports, it has been recommended that ginkgo not be used with aspirin, warfarin, dipyridamole, clopidogrel, ticlopidine, and heparin (Cupp 1999; Miller 1998).

Carbamazepine; Sodium Valproate

A study evaluating the effects of Ginkgo biloba in mice treated with the anticonvulsants sodium valproate and carbamazepine found that intraperitoneal administration of ginkgo (50 mg/kg) decreased the protective effect of these medications on picrotoxin- (2 mg/kg) and strychnine- (0.25 mg/kg) induced convulsions (Manocha et al. 1996). This was thought to be related to antagonism of PAF and possible effects on the GABA-ergic system. High dose Ginkgo biloba could decrease the effectiveness of anticonvulsant therapy in patients with coexisting symptoms of cerebral insufficiency.

Cyclosporine

In an in vitro study, cyclosporin (CsA) stimulated lipid peroxidation up to 10 times the control value (Barth et al. 1991). Ginkgo biloba extract added to the medium inhibited CsA-induced lipid peroxidation in a concentration-dependent manner. Ginkgo biloba extract may be able to prevent CsA mediated free radical damage to human membranes. More research is necessary to fully evaluate the safety and efficacy of this application of GBE.

Papaverine

It has been reported that ginkgo extract has the ability to potentiate the intracavernosal injection of papaverine for impotence (Sikora et al. 1989). For patients with arterial erectile dysfunction who did not respond to papaverine alone, 50% of patients responded to treatment with ginkgo alone and 20% of patients responded sufficiently to the combination of ginkgo and papaverine.

Thiazide Diuretics

A 5-year toxicological study on traditional remedies and food supplements reported one case of an interaction between Ginkgo biloba and thiazide diuretics (Shaw et al. 1991). A patient taking thiazide diuretics was reported to have increased blood pressure one week after adding Ginkgo biloba to her treatment regimen. Blood pressure returned to pre-treatment levels when both the diuretic and ginkgo were discontinued. However, Ginkgo biloba has not been reported to increase blood pressure levels in any clinical trials.

Trazodone

According to a recent case report, flavonoids in Ginkgo biloba may increase the sedative effects of the drug trazodone (Galluzzi et al. 2000). The report describes the case of an 80-year-old Alzheimer's patient who, after taking trazodone (20 mg bid) with gingko extract (80 mg bid) for 3 days, went into a coma. The patient was revived and experienced no permanent damage. It is possible that the mechanism for this interaction involves the ability of the ginkgo flavonoids to increase the metabolism of trazodone (leading to active metabolites) and activity at the benzodiazepine binding sites. Further studies are needed to confirm this report.

References

Barth SA, Inselmann G, Engemann R, Heidemann HT. Influences of Ginkgo biloba on cyclosporin A induced lipid peroxidation in human liver microsomes in comparison to vitamin E, glutathione and N-Acetylcysteine. Biochem Pharmacol. 1991;41(10):1521-1526.

Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam Physician. 1999;59(5):1239-1244.

Fugh-Berman A. Herb-drug interactions. Lancet. 2000;355(9198):134-138.

Galluzzi S, Zanetti O, Binetti G, Trabucchi M, Frisoni GB. Coma in a patient with Alzheimer's disease taking low dose trazodone and Ginkgo biloba. J Neurol Neurosurg Psychiatry. 2000;68:679-683.

Kim YS, Pyo MK, Park KM, et al. Antiplatelet and antithrombotic effects of a combination of ticlopidine and Ginkgo biloba ext (EGb 761). Thromb Res. 1998;91:33-38.

Manocha A, Pillai KK, Husain SZ. Influence of Ginkgo biloba on the effect of anticonvulsants. Indian J Pharmacol. 1996;28:84-87.

Matthews MK. Association of Ginkgo biloba with intracerebral hemorrhage [letter]. Neurol. 1998;50(6):1933-1934.

Miller LC. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158(9):2200-2211.

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

Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements. A 5 year toxicological study (1991-1995). Drug Safety. 1997;17(5):342-356.

Sikora R, Sohn M, Deutz F-J, et al. Ginkgo biloba extract in the therapy of erectile dysfunction. J Urol. 1989;141:188A.

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