Warfarin with Sulfasalazine Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Sulfasalazine
- Azulfidine®
- Azulfidine® EN-tabs®
- Sulfasalazine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
Increased risk of bleeding or reduced efficacy of warfarin
Interaction Summary
Concomitant use of sulfasalazine and warfarin may increase the risk of bleeding. A 60-year-old man treated with warfarin had approximately a 3-fold increase in INR and new-onset bruising within 30 days of initiating sulfasalazine for inflammatory bowel disease. Conversely, warfarin resistance with concomitant sulfasalazine has been reported. A 37-year-old woman experienced a DVT following consistent subtherapeutic INR levels despite approximately a 150% increase in warfarin dosage after initiating sulfasalazine for progressive arthritis and ulcerative colitis . If concomitant use of sulfasalazine and warfarin is required, additional prothrombin time and INR monitoring may be warranted.
Severity
Moderate
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Concomitant use of sulfasalazine and warfarin may potentiate warfarin anticoagulant effects or may cause sulfasalazine-induced warfarin resistance . If concomitant administration of sulfasalazine and warfarin is required, additional prothrombin time and INR monitoring may be warranted.
Mechanism Of Interaction
Unknown
Literature Reports
A) Concomitant use of sulfasalazine and warfarin resulted in approximately a 3-fold increase in INR in a 60-year-old man. The patient received warfarin 40 mg/week for mechanical aortic and mitral value replacements and his INR was stable. He started sulfasalazine 500 mg twice daily for 7 days, then 500 mg 4 times daily thereafter for inflammatory bowel disease. Three days after sulfasalazine initiation, his INR was 2.2 and his warfarin dose was increased to 42.5 mg/week. At his next clinic visit 22 days later, his INR was 6.1 and he had new-onset bruising. He reported no other symptoms, medication or diet changes, or alcohol ingestion. A sulfasalazine-warfarin interaction was suspected, sulfasalazine was discontinued, and warfarin was held for 3 days then resumed at 42.5 mg/week. In 1 week, his INR was 1.9 and 2 weeks later, his INR was in therapeutic range .
B) Concomitant sulfasalazine and warfarin was associated with warfarin resistance in a 37-year-old woman. Relevant medical history included ulcerative colitis treated with azathioprine 125 mg/day and 5-aminosalicyclic acid 1600 mg twice daily; arthritis treated with enteric-coated aspirin 325 mg/day; recurrent thromboembolic events treated with stable doses of warfarin (30 mg/wk); and taking oral contraceptives. On admission for joint aches/pain, progressive arthritis was diagnosed, 5-aminosalicyclic acid was discontinued, and sulfasalazine 1000 mg 4 times daily was initiated. Two weeks before starting and a day after starting sulfasalazine the INR was 2.7 and 1.5, respectively. The warfarin dose was subsequently increased. Within 30 days of starting sulfasalazine, a Doppler ultrasound showed a new DVT in her right popliteal vein and her INR was 1.4 with warfarin 40 mg/week. The DVT was treated and warfarin was increased to 52.5 mg/week, but her INR remained subtherapeutic. About 11 days later, her INR reached therapeutic range with warfarin 75 mg/week. The sulfasalazine was eventually switched back to 5-aminosalicyclic acid and her warfarin requirements reduced to less than 45 mg/week. Due to subtherapeutic INR levels with approximately a 150% increase in warfarin dosage, a sulfasalazine-induced warfarin resistance was suspected and the interaction was rated as probable on the Naranjo probability scale .
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.
Sulfasalazine Overview
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Sulfasalazine is used to treat ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum) and also to maintain improvement of ulcerative colitis symptoms. Sulfasalazine delayed-release (Azulfidine EN-tabs) is also used to treat rheumatoid arthritis in adults whose disease has not responded well to other medications or could not be tolerated. Sulfasalazine delayed-release (Azulfidine EN-tabs) is also used to treat polyarticular juvenile idiopathic arthritis (PJIA; a type of childhood arthritis that affects five or more joints during the first six months of the condition, causing pain, swelling, and loss of function) in children who have not been helped by other medications. Sulfasalazine is in a class of medications called anti-inflammatory drugs. It works by reducing inflammation (swelling) inside the body.
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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.