Ginkgo - Xarelto (Rivaroxaban) Interaction

Interaction Details

Rivaroxaban 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.
• Bai J, Zhang C. Metabolic interaction between biflavonoids in Ginkgo biloba leaves and tacrolimus. Biopharm Drug Dispos 2023;44(2):157-164.

Interaction Details

Rivaroxaban is classified as belonging to the following category: P-Glycoprotein Substrates

Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.
A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect.

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

• Fan, L., Tao, G. Y., Wang, G., Chen, Y., Zhang, W., He, Y. J., Li, Q., Lei, H. P., Jiang, F., Hu, D. L., Huang, Y. F., and Zhou, H. H. Effects of Ginkgo biloba extract ingestion on the pharmacokinetics of talinolol in healthy Chinese volunteers. Ann Phar

Interaction Details

Rivaroxaban 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.

Rivaroxaban Overview

• Rivaroxaban is used to treat deep vein thrombosis (DVT; a blood clot, usually in the leg) and pulmonary embolism (PE; a blood clot in the lung) in adults. Rivaroxaban is also used to prevent DVT and PE from happening again after initial treatment is completed in adults. It is also used to help prevent strokes or serious blood clots in adults who have atrial fibrillation (a condition in which the heart beats irregularly, increasing the chance of clots forming in the body, and possibly causing strokes) that is not caused by heart valve disease. Rivaroxaban is also used to prevent DVT and PE in adults who are having hip replacement or knee replacement surgery or in people who are hospitalized for serious illnesses and are at risk of developing a clot due to decreased ability to move around or other risk factors. It is also used along with aspirin to lower the risk of a heart attack, stroke, or death in adults with coronary artery disease (narrowing of the blood vessels that supply blood to the heart) or peripheral arterial disease (poor circulation in the blood vessels that supply blood to the arms and legs). Rivaroxaban is also used to treat and prevent DVT and PE from happening again in children and certain infants who have received at least 5 days of initial anticoagulation (blood thinner) treatment. It is also used to prevent DVT and PE after heart surgery in children 2 years of age or older who have congenital heart disease (abnormality in the heart that develops before birth). Rivaroxaban is in a class of medications called factor Xa inhibitors. It works by blocking the action of a certain natural substance that helps blood clots to form.

Ginkgo - More Interactions

Ginkgo interacts with 1236 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.