Warfarin with Sulfinpyrazone Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Sulfinpyrazone
- Anturane®
- Sulfinpyrazone
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
In patients maintained on warfarin, sulfinpyrazone has been reported to greatly enhance the hypoprothrombinemic effects of warfarin. Sulfinpyrazone increases the effects of warfarin primarily by inhibiting the cytochrome P-450-mediated oxidation of (S)-warfarin, the more potent enantiomer .
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 sulfinpyrazone, 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
Inhibition of oxidative metabolism of the S-warfarin enantiomer
Literature Reports
A) In a blinded, randomized study, the effect of sulfinpyrazone 200 mg four times daily on prothrombin activity in six patients on warfarin versus five patients taking placebo was demonstrated . The average daily warfarin dose required to maintain adequate anticoagulation in patients receiving both drugs was about half that of the warfarin/placebo group, whereas the average daily dose had previously been the same in both groups. The difference between groups was statistically significant.
B) The effect of sulfinpyrazone 200 mg every six hours upon the prothrombin time and subsequent warfarin dose in five patients stabilized for at least six months on oral warfarin therapy was investigated . Sulfinpyrazone necessitated a mean warfarin dose reduction of 46% to keep the prothrombin time from exceeding 3.5 times control. The warfarin dose returned to pre-study amounts within one to two weeks after the discontinuation of sulfinpyrazone. The protein binding of warfarin, and the concentration of racemic warfarin was not changed during sulfinpyrazone administration. Sulfinpyrazone does not interact with the anticoagulant phenprocoumon .
C) Sulfinpyrazone augments the hypoprothrombinemic effect of warfarin by prolonging the half-life of the more potent S-warfarin isomer . In six normal subjects, sulfinpyrazone pre-treatment caused an increase in S-warfarin half-life from 32 to 51 hours with a significant increase in the resulting prothrombin time. The half-life of R-warfarin decreased slightly and no effect on the prothrombin time response to the R-isomer was observed. Sulfinpyrazone interacts with warfarin by inhibiting S-warfarin metabolism.
D) The effects of sulfinpyrazone upon R- and S-warfarin protein binding in vitro were examined . R-isomer percentage bound decreased from 99.15% to 98.73%, and S-isomer binding decreased from 99.47% to 99.42%. These changes in stereoselective protein binding displacement may have an effect on the clearance of each isomer. The major mechanism of the sulfinpyrazone-warfarin interaction remains, however, to be the inhibition of metabolism of the more potent S-warfarin isomer by sulfinpyrazone. At low sulfinpyrazone concentrations, it appears that one molecule of sulfinpyrazone displaces one molecule of warfarin from albumin in vitro .
E) The stereochemical consideration in the warfarin-sulfinpyrazone interaction has been reported . Pharmacokinetic analysis of the data suggests the following: at least four distinct enzymes (two oxidases and two reductases) are involved in the metabolism of warfarin. Sulfinpyrazone increases the hypoprothrombinemia caused by warfarin primarily by inhibition of the cytochrome P-450-mediated oxidation of S-warfarin, the biologically more potent enantiomer. The increased clearance of R-warfarin results not from induction, but from its selective displacement from plasma protein binding sites.
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.
Sulfinpyrazone Overview
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Sulfinpyrazone is used to treat gouty arthritis. It works by lowering the amount of uric acid in your blood, preventing gout attacks. The drug helps prevent attacks but will not treat an attack once it has started.
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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.