Danshen - Coumadin (Warfarin Sodium) Interaction

Interaction Details

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

Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that danshen tincture and various constituents of danshen inhibit the activity of CYP1A2. However, this activity has not been shown in humans when theophylline, a CYP1A2 substrate, was used as a target drug.

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

• Wang X, Cheung CM, Lee WY, Or PM, Yeung JH. Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine. 2010 Sep;17(11):868-75.
• Wang X, Yeung JH. Investigation of cytochrome P450 1A2 and 3A inhibitory properties of Danshen tincture. Phytomedicine. 2012 Feb 15;19(3-4):348-54.
• Zhou X, Chan K, Yeung JH. Herb-drug interactions with Danshen (Salvia miltiorrhiza): a review on the role of cytochrome P450 enzymes. Drug Metabol Drug Interact. 2012 Mar 2;27(1):9-18.

Interaction Details

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

Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2C9.
In vitro research shows that various constituents of danshen inhibit the activity of CYP2C9. So far, this interaction has not been reported in humans.

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

• Wang X, Cheung CM, Lee WY, Or PM, Yeung JH. Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine. 2010 Sep;17(11):868-75.

Interaction Details

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

Danshen might alter the levels and clinical effects of drugs metabolized by CYP3A4.
Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases the clearance of midazolam, a CYP3A4 substrate. The maximum concentration of midazolam was decreased by 31% to 67%, and drug levels were decreased by 27% to 80%. However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87%.

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

• Qiu F, Wang G, Zhang R, Sun J, et al. Effect of danshen extract on the activity of CYP3A4 in healthy volunteers. Br J Clin Pharmacol 2010;69:656-62.
• Qiu F, Jiang J, Ma Y, Wang G, Gao C, Zhang X, Zhang L, Liu S, He M, Zhu L, Ye Y, Li Q, Miao P. Opposite Effects of Single-Dose and Multidose Administration of the Ethanol Extract of Danshen on CYP3A in Healthy Volunteers. Evid Based Complement Alternat Me

Interaction Details

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

Theoretically, danshen may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Danshen has been reported to have antithrombotic effects.

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

• Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7.
• Yin QS, Chen L, Mi RH, Ai H, Yin JJ, Liu XJ, Wei XD. Efficacy and safety of danshen compound tablets in preventing thalidomide-associated thromboembolism in patients with multiple myeloma: a multicenter retrospective study. Med Sci Monit. 2016 Oct 20;22:3

Interaction Details

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

Theoretically, danshen may increase the risk of bleeding if used with warfarin.
There have been several case reports of increased international normalized ratio (INR) after concomitant use of danshen and warfarin. Elevations in INR have occurred as early as 3-5 days after start of danshen. However, a clinical trial in adults taking warfarin with stable INR found that the addition of compound danshen dripping pills, containing danshen extract, Panax notoginseng, and borneol, 270 mg three times daily for 4 weeks did not alter INR levels or the average required warfarin dose when compared to baseline. These findings are consistent with animal research, which found no change in warfarin pharmacokinetics with the use of danshen. Other research in healthy adult males also shows that taking a combination of danshen and kudzu with warfarin does not increases plasma warfarin area under the curve, but may reduce plasma soluble thrombomodulin levels. However, other research shows that danshen might increase the rate of absorption and decrease the elimination rate of warfarin. Also, research in healthy adult males shows that taking a combination of danshen and kudzu with warfarin increases plasma area under the curve of danshensu, a constituent of danshen, by approximately 29.5-fold. Danshen should be used cautiously in patients taking warfarin.

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

• Yu CM, Chan JC, Sanderson JE. Chinese herbs and warfarin potentiation by danshen. J Intern Med 1997;241:337-9.
• Tam LS, et al. Warfarin interacions with Chinese traditional medicines: danshen and methyl salicylate medicated oil. Aust N Z J Med 1995;25:258.
• Chan TY. Interaction between warfarin and danshen (Salvia miltiorrhiza). Ann Pharmacother 2001;35:501-4.
• Chan TY. Drug interactions as a cause of overanticoagulation and bleedings in Chinese patients receiving warfarin. Int J Clin Pharmacol Ther 1998;36:403-5.
• Izzat MB, Yim APC, El-Zufari MH. A taste of Chinese medicine! Ann Thorac Surg 1998;66:941-2.
• Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7.
• Chu Y, Zhang L, Wang XY, Guo JH, Guo ZX, Ma XH. The effect of Compound Danshen Dripping Pills, a Chinese herb medicine, on the pharmacokinetics and pharmacodynamics of warfarin in rats. J Ethnopharmacol. 2011 Oct 11;137(3):1457-61.
• Zhang Z, Ge B, Zhou L, Lam TN, Zuo Z. Induction of liver cytochrome P450s by Danshen-Gegen formula is the leading cause for its pharmacokinetic interactions with warfarin. J Ethnopharmacol. 2014 Jul 3;154(3):672-86.
• Zhou X, Chan K, Yeung JH. Herb-drug interactions with Danshen (Salvia miltiorrhiza): a review on the role of cytochrome P450 enzymes. Drug Metabol Drug Interact. 2012 Mar 2;27(1):9-18.
• Zhou L, Wang S, Zhang Z, Lau BS, Fung KP, Leung PC, Zuo Z. Pharmacokinetic and pharmacodynamic interaction of Danshen-Gegen extract with warfarin and aspirin. J Ethnopharmacol. 2012 Sep 28;143(2):648-55.
• Lv C, Liu C, Yao Z, et al. The clinical pharmacokinetics and pharmacodynamics of warfarin when combined with compound danshen: a case study for combined treatment of coronary heart diseases with atrial fibrillation. Front Pharmacol. 2017 Nov 21;8:826.
• Zhang Y, Yang M, Ho NJ, et al. Is it safe to take Radix Salvia Miltiorrhiza - Radix Pueraria Lobate product with warfarin and aspirin? A pilot study in healthy human subjects. J Ethnopharmacol. 2020 Nov 15;262:113151.

Warfarin Sodium 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.

Danshen - More Interactions

Danshen interacts with 1011 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.