Ginkgo - Warfarin Interaction

Interaction Details

Warfarin is classified as belonging to the following category: Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes. However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19.

Interaction Rating

Likelihood of Occurrence

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.

References

• Yin OQ, Tomlinson B, Waye MM, et al. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics 2004;14:841-50.
• Lei, H. P., Wang, G., Wang, L. S., Ou-yang, D. S., Chen, H., Li, Q., Zhang, W., Tan, Z. R., Fan, L., He, Y. J., and Zhou, H. H. Lack of effect of Ginkgo biloba on voriconazole pharmacokinetics in Chinese volunteers identified as CYP2C19 poor and extensiv

Interaction Details

Warfarin is classified as belonging to the following category: Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.
Laboratory research suggests that ginkgo leaf extract can mildly inhibit CYP1A2 enzymes. However, clinical research suggests ginkgo might not affect CYP1A2. Until more is known, use ginkgo cautiously in patients taking drugs metabolized by these enzymes.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Gurley BJ, Gardner SF, Hubbard MA. Clinical assessment of potential cytochrome P450-mediated herb-drug interactions. AAPS Ann Mtg & Expo Indianapolis, IN: 2000; Oct 29 - Nov 2:presentation #3460.
• Galluzzi S, Zanetti O, Binetti G, et al. Coma in a patient with Alzheimer's disease taking low dose trazodone and Ginkgo biloba. J Neurol Neurosurg Psychiatry 2000;68:679-80.
• Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82.
• Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87..

Interaction Details

Warfarin is classified as belonging to the following category: Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C9.
In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity . The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005;11:433-9.
• Gaudineau C, Beckerman R, Welbourn S, Auclair K. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Comm 2004;318:1072–8.
• Mohutsky MA, Anderson GD, Miller JW, Elmer GW. Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo. Am J Ther 2006;13:24-31.

Interaction Details

Warfarin is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.
There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4. Ginkgo does not appear to affect hepatic CYP3A4. However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates. Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity. However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4).

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Gurley BJ, Gardner SF, Hubbard MA. Clinical assessment of potential cytochrome P450-mediated herb-drug interactions. AAPS Ann Mtg & Expo Indianapolis, IN: 2000; Oct 29 - Nov 2:presentation #3460.
• Galluzzi S, Zanetti O, Binetti G, et al. Coma in a patient with Alzheimer's disease taking low dose trazodone and Ginkgo biloba. J Neurol Neurosurg Psychiatry 2000;68:679-80.
• Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82.
• Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87..
• Yale SH, Glurich I. Analysis of the inhibitory potential of Ginkgo biloba, Echinacea purpurea, and Serenoa repens on the metabolic activity of cytochrome P450 3A4, 2D6, and 2C9. J Altern Complement Med 2005;11:433-9.
• Yasui-Furukori N, Furukori H, Kaneda A, et al. The effects of Ginkgo biloba extracts on the pharmacokinetics and pharmacodynamics of donepezil. J Clin Pharmacol 2004;44:538-42.
• Markowitz JS, Donovan JL, Lindsay DeVane C, et al. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol 2003;23:576-81.
• Wiegman DJ, Brinkman K, Franssen EJ. Interaction of Ginkgo biloba with efavirenz. AIDS 2009;23:1184-5.
• Naccarato M, Yoong D, Gough K. A potential drug-herbal interaction between Ginkgo biloba and efavirenz. J Int Assoc Physicians AIDS Care (Chic). 2012;11(2):98-100. doi: 10.1177/1545109711435364. Epub 2012 Feb 9.
• Robertson, S. M., Davey, R. T., Voell, J., Formentini, E., Alfaro, R. M., and Penzak, S. R. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin 2008;24(2):591-599.
• Penzak, S. R., Busse, K. H., Robertson, S. M., Formentini, E., Alfaro, R. M., and Davey, R. T., Jr. Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions. J Clin Pharmacol 2008;48(6):671-680.
• Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15.

Interaction Details

Warfarin is classified as belonging to the following category: Anticoagulant/Antiplatelet Drugs

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting. A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time. An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin. It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation. However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. In addition, a single dose of ginkgo plus clopidogrel or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation. Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Benjamin J, Muir T, Briggs K, Pentland B. A case of cerebral haemorrhage-can Ginkgo biloba be implicated? Postgrad Med J 2001;77:112-3.
• Rowin J, Lewis SL. Spontaneous bilateral subdural hemotomas with chronic Ginkgo biloba ingestion. Neurology 1996;46:1775-6.
• Rosenblatt M, Mindel T. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med 1997;336:1108.
• Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7.
• Miller LG, Freeman B. Possible subdural hematoma associated with Ginkgo biloba. J Herb Pharmacother 2002;2:57-63.
• Kudolo GB, Dorsey S, Blodgett J. Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects. Thromb Res 2002;108:151-60..
• Kohler S, Funk P, Kieser M. Influence of a 7-day treatment with Ginkgo biloba special extract EGb 761 on bleeding time and coagulation: a randomized, placebo-controlled, double-blind study in healthy volunteers. Blood Coagul Fibrinolysis 2004;15:303–9.
• Destro MW, Speranzini MB, Cavalheiro Filho C, et al. Bilateral haematoma after rhytidoplasty and blepharoplasty following chronic use of Ginkgo biloba. Br J Plast Surg 2005;58:100-1.
• Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med 2005;20;657-61.
• Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis 2003;167:367.
• Bebbington A, Kulkarni R, Roberts P. Ginkgo biloba: Persistent bleeding after total hip arthroplasty caused by herbal self-medication. J Arthroplasty 2005;20:125-6. .
• Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 1998;352:36.
• Aruna D, Naidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol 2007;63:333-8.
• Kim BH, Kim KP, Lim KS, et al. Influence of Ginkgo biloba extract on the pharmacodynamic effects and pharmacokinetic properties of ticlopidine: An open-label, randomized, two-period, two-treatment, two-sequence, single-dose crossover study in healthy Kor
• Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy 2011;31:490-502.
• Bal Dit, Sollier C., Caplain, H., and Drouet, L. No alteration in platelet function or coagulation induced by EGb761 in a controlled study. Clin Lab Haematol. 2003;25(4):251-253.
• Kim, T. E., Kim, B. H., Kim, J., Kim, K. P., Yi, S., Shin, H. S., Lee, Y. O., Lee, K. H., Shin, S. G., Jang, I. J., and Yu, K. S. Comparison of the pharmacokinetics of ticlopidine between administration of a combined fixed-dose tablet formulation of ticl
• Pedroso, J. L., Henriques Aquino, C. C., Escorcio Bezerra, M. L., Baiense, R. F., Suarez, M. M., Dutra, L. A., Braga-Neto, P., and Povoas Barsottini, O. G. Ginkgo biloba and cerebral bleeding: a case report and critical review. Neurologist. 2011;17(2):89
• Stoddard GJ, Archer M, Shane-McWhorter L, Bray BE, Redd DF, Proulx J, Zeng-Treitler Q. Ginkgo and Warfarin Interaction in a Large Veterans Administration Population. AMIA Annu Symp Proc. 2015 Nov 5;2015:1174-83.
• Hoerr R, Zimmermann A, Seitz F, Dienel A. Single and repeated doses of EGb 761® do not affect pharmacokinetics or pharmacodynamics of rivaroxaban in healthy subjects. Front Pharmacol. 2022 Apr 20;13:868843.

Interaction Details

Warfarin is classified as belonging to the following category: Warfarin (Coumadin)

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38%. There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels. However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Benjamin J, Muir T, Briggs K, Pentland B. A case of cerebral haemorrhage-can Ginkgo biloba be implicated? Postgrad Med J 2001;77:112-3.
• Matthews, MK. Association of Ginkgo biloba with intracerebral hemorrhage. Neurology 1998;50:1934.
• Rowin J, Lewis SL. Spontaneous bilateral subdural hemotomas with chronic Ginkgo biloba ingestion. Neurology 1996;46:1775-6.
• Rosenblatt M, Mindel T. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med 1997;336:1108.
• Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7.
• Miller LG, Freeman B. Possible subdural hematoma associated with Ginkgo biloba. J Herb Pharmacother 2002;2:57-63.
• Kudolo GB, Dorsey S, Blodgett J. Effect of the ingestion of Ginkgo biloba extract on platelet aggregation and urinary prostanoid excretion in healthy and Type 2 diabetic subjects. Thromb Res 2002;108:151-60..
• Engelsen J, Nielsen JD, Winther K. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost 2002;87:1075-6.
• Gaudineau C, Beckerman R, Welbourn S, Auclair K. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Comm 2004;318:1072–8.
• Jiang X, Williams KM, Liauw WS, et al. Effect of ginkgo and ginger on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2005;59:425-32.
• Destro MW, Speranzini MB, Cavalheiro Filho C, et al. Bilateral haematoma after rhytidoplasty and blepharoplasty following chronic use of Ginkgo biloba. Br J Plast Surg 2005;58:100-1.
• Bent S, Goldberg H, Padula A, Avins AL. Spontaneous bleeding associated with Ginkgo biloba: a case report and systematic review of the literature. J Gen Intern Med 2005;20;657-61.
• Meisel C, Johne A, Roots I. Fatal intracerebral mass bleeding associated with Ginkgo biloba and ibuprofen. Atherosclerosis 2003;167:367.
• Bebbington A, Kulkarni R, Roberts P. Ginkgo biloba: Persistent bleeding after total hip arthroplasty caused by herbal self-medication. J Arthroplasty 2005;20:125-6. .
• Vale S. Subarachnoid haemorrhage associated with Ginkgo biloba. Lancet 1998;352:36.
• Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8.
• Kellermann AJ, Kloft C. Is there a risk of bleeding associated with standardized ginkgo biloba extract therapy? A systematic review and meta-analysis. Pharmacotherapy 2011;31:490-502.
• Engelsen, J., Nielsen, J. D., and Hansen, K. F. [Effect of Coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial]. Ugeskr.Laeger 4-28-2003;165(18):18
• Pedroso, J. L., Henriques Aquino, C. C., Escorcio Bezerra, M. L., Baiense, R. F., Suarez, M. M., Dutra, L. A., Braga-Neto, P., and Povoas Barsottini, O. G. Ginkgo biloba and cerebral bleeding: a case report and critical review. Neurologist. 2011;17(2):89
• Zhou, Y. and Zeng, R. [Effects of Ginkgo biloba extract on anticoagulation and blood drug level of warfarin in healthy wolunteers]. Zhongguo Zhong Yao Za Zhi 2011;36(16):2290-2293.
• Stoddard GJ, Archer M, Shane-McWhorter L, Bray BE, Redd DF, Proulx J, Zeng-Treitler Q. Ginkgo and Warfarin Interaction in a Large Veterans Administration Population. AMIA Annu Symp Proc. 2015 Nov 5;2015:1174-83.

Warfarin Overview

• Warfarin is used to prevent blood clots from forming or growing larger in your blood and blood vessels. It is prescribed for people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. Warfarin is also used to treat or prevent venous thrombosis (swelling and blood clot in a vein) and pulmonary embolism (a blood clot in the lung). Warfarin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood.

Ginkgo - More Interactions

Ginkgo interacts with 1216 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.