Warfarin with Disulfiram Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Disulfiram
- Antabuse®
- Disulfiram
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Concomitant disulfiram and warfarin therapy has resulted in a potentiation of warfarin's hypoprothrombinemic effect. Disulfiram may augment the anticoagulant effect of warfarin by directly affecting the hepatic mechanism responsible for hypoprothrombinemia.
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
In patients receiving oral anticoagulant therapy with warfarin, the prothrombin time ratio or international normalized ratio (INR) should be closely monitored with the addition and withdrawal of treatment with disulfiram, and should be reassessed periodically during concurrent therapy. Adjustments of the warfarin dose may be necessary in order to maintain the desired level of anticoagulation.
Mechanism Of Interaction
Decreased warfarin metabolism
Literature Reports
A) The effects of concomitant warfarin and disulfiram were studied in seven subjects who served as their own controls. The AUC of one-stage prothrombin times for the S-enantiomer of warfarin increased by 67% when both drugs were given compared to S-warfarin alone. No change in this measure of hypoprothrombinemic status was seen with the R-enantiomer. Because no change in plasma concentrations of the warfarin enantiomers was seen, it was suggested that the impact of concomitant use of these drugs on hypoprothrombinemia was due to a direct effect of disulfiram on the hepatic mechanism responsible for hypoprothrombinemia. Further study is needed .
B) A controlled clinical trial was conducted evaluating the concomitant use of these two drugs in 8 healthy volunteers. Patients served as their own controls and received warfarin as a single large dose (1.5 mg/kg) or over 21 days as 15 mg for three days followed by a maintenance dose of 7 mg daily. Patients received warfarin alone or in combination with disulfiram. With concurrent administration, an increase in the plasma level and hypoprothrombinemic effect of warfarin was noted in seven patients with the single dose and in six patients with the 21-day regimen. Disulfiram appeared to inhibit the metabolism of warfarin .
C) A case of disulfiram increasing the hypoprothrombinemic effect of warfarin was reported. Adequate anticoagulant therapy was established with warfarin 7.5 and 10 mg on alternate days. When 250 mg daily of disulfiram was added, prothrombin percentages fell and the patient hemorrhaged. A similar response was noted on two other occasions with disulfiram 250 mg every other day .
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.
Disulfiram Overview
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Disulfiram is used to treat chronic alcoholism. It causes unpleasant effects when even small amounts of alcohol are consumed. These effects include flushing of the face, headache, nausea, vomiting, chest pain, weakness, blurred vision, mental confusion, sweating, choking, breathing difficulty, and anxiety. These effects begin about 10 minutes after alcohol enters the body and last for 1 hour or more. Disulfiram is not a cure for alcoholism, but discourages drinking.
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This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
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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.