Warfarin with Tan-Shen Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
Increased risk of bleeding
Interaction Summary
Human cases with concomitant use of warfarin and tan-shen report greatly elevated International Normalized Ratio (INR) and bleeding complications. In animals, tan-shen increased warfarin AUC and Cmax as well as prothrombin time (PT) . In vitro, tan-shen extracts alone have shown inhibition of platelet aggregation .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Avoid concomitant administration of anticoagulants with tan-shen regardless of tan-shen dosage form (i.e., orally or as cigarettes).
Mechanism Of Interaction
Increased serum concentration and bioavailability of anticoagulants
Literature Reports
A) A 62-year-old man had been stabilized on warfarin 5 mg orally daily for mechanical valve prosthesis with an associated International Normalized Ratio (INR) of 3.0. The patient was also taking digoxin 0.25 mg, captopril 75 mg and furosemide 40 mg daily. Follow-up visits at 2 weeks and 4 weeks required no warfarin dose adjustment. At 6 weeks, he was admitted through the emergency room for massive right pleural effusion and an INR of 8.4. A detailed history revealed that he had begun taking tan-shen tea for "mending his heart" approximately two weeks prior to admission. With warfarin and tan-shen discontinuation, administration of 6 units of fresh frozen plasma and 7 units of packed red blood cells, and drainage of 4.5 L of nonclotted blood from a right pleural drain, the INR was brought down to 2.0 and the patient was stabilized .
B) In a letter-to-the-editor in response to the report, it was noted that tan-shen, the root of Salvia miltiorrhiza, is not only available for oral intake but also is inhaled. It has been incorporated into some Chinese cigarettes .
C) A 48-year-old woman with rheumatic heart disease with atrial fibrillation and mitral stenosis since age 26 underwent percutaneous transvenous mitral valvuloplasty with subsequent warfarin administration. Warfarin required frequent dose adjustments over the ensuing 14 months. One month prior to admission, INR was 1.35 and the warfarin dose was increased to 4 mg daily. The patient reported to the emergency room with dyspnea and atrial fibrillation with a prothrombin time (PT) exceeding 60 seconds and INR 5.62. The patient admitted to using tan-shen every day for the month preceding admission. The clotting abnormality persisted for 5 days. With resumption of warfarin at 3 mg daily, her INR stabilized at 2.5. Tan-shen was not reintroduced .
D) A 66-year-old male stabilized on warfarin with an International Normalized Ratio (INR) of approximately 2 experienced bleeding complications following use of methyl salicylate medicated oil and tan-shen. On admission, the INR was greater than 5.5, activated partial thromboplastin time was 43.7 seconds, and hemoglobin was 7.6 grams/deciliter. The patient had been experiencing melena for the previous two days. Other medications were digoxin 0.25 mg daily and propranolol 5 mg twice daily. Nine days prior to admission, the patient began treating non-specific left-sided chest wall pain with "Kwan Loong Medicated Oil" containing 15% methyl salicylate topically two to three times daily. Five and three days prior to admission, he drank a decoction of tan-shen. Gastroscopy revealed bleeding from a gastric carcinoma. Warfarin was stopped and 12 units of fresh frozen plasma and 7 units of packed cells were required to normalize the INR. This case of bleeding was attributed to an interaction between tan-shen, Kwan Loong Medicated Oil, and warfarin .
E) Tan-shen extract changed the concentration and effects of warfarin when given intraperitoneally to rats in doses of 5 grams/kg twice daily for 3 days followed by a single oral dose of 2 mg/kg racemic warfarin. Both R- and S-warfarin had increased rate of absorption, AUC, maximum concentration, and elimination half-life and decreased clearance and volume of distribution. This produced significantly increased plasma concentrations for 24 hours and prothrombin time for 2 days. The increased concentrations and prothrombin time also occurred with steady-state levels of racemic warfarin when it was given in doses of 0.2 mg/kg/day for 5 days and followed by tan-shen extract 2 g/kg twice daily for three days with warfarin treatment continuing .
F) Within 48 hours of a single warfarin dose in rats administered tan-shen, area under the curve (AUC) of warfarin was increased, half-life was decreased, and maximum concentration nearly doubled; prothrombin time was also increased. Tan-shen, authenticated pharmacognostically, was administered to 10 rats in a fixed dose of 5 g/kg twice daily intraperitoneally. Three days later a single oral dose of warfarin (2 mg/kg) was then administered. AUC increased from 154.8 mcg/mL/hr to 269.5 mcg/mL/hr (p less than 0.005), half-life decreased from 31.8 hr to 16.0 hr (p less than 0.001) and Cmax increased from 5500 ng/mL to 10,976 g/mL (p less than 0.001). Volume of distribution was significantly decreased from 142.5 mL to 54.4 mL (p less than 0.005). Clearance was nonsignificantly decreased from 3.53 mL/hr to 2.23 mL/hr. The authors concluded that tan-shen affected warfarin bioavailability initially and the shortened elimination half-life was due to the decrease in volume of distribution since the change in clearance was not considered significant. The prothrombin time when on warfarin alone was 41.1 seconds versus 49.9 seconds (p less than 0.001) with concomitant tan-shen administration .
Warfarin Overview
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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.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.