Warfarin with Methyl Salicylate Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Concomitant use of topical methyl salicylate and systemic warfarin may result in increased INR/PT response rates. Several cases of warfarin potentiation have been documented with concurrent use of topical methyl salicylate and warfarin .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of topical methyl salicylate and systemic warfarin may result in increased INR/PT response rates. Concurrent use of topical salicylates in patients taking warfarin should be avoided. Prescribing clinicians and their patients who are being treated with warfarin should be advised of this interaction. Topical capsaicin ointment is a preferable alternative.
Mechanism Of Interaction
Inhibition of warfarin metabolism
Literature Reports
A) A case report described retroperitoneal bleeding in a 53-year-old man following concomitant use of warfarin and topical methyl salicylate ointment. The patient was admitted to the hospital with a 2-day history of exacerbation of COPD, cor pulmonale and right leg swelling/pain. On day 13, warfarin therapy was initiated at 5 mg/day and reduced to 2 mg/day on days 15 and 16. His INRs were 2.14 and 2.66 on days 15 and 16. The patient had been receiving warfarin for 5 days when he fell and suffered a concussion to the right flank. From day 16 to 17, his Hgb level decreased to 9.7 g/dL. One day later, his INR had increased from 2.46 to between 3.49 and 3.71. On further questioning, the patient conceded to applying 20 g of 50% methyl salicylate topical ointment over his right calf on days 15 through 17. A large right retroperitoneal hematoma was identified on CT scan. Subsequently, 12 units of fresh frozen plasma and 4 units of packed cells were given and his INR was 1.5 to 1.79. On day 19 following another transfusion of plasma and packed cells, his INR decreased from 2.05 to 1.45. On day 20, he was given vitamin K IV 2.5 mg in addition to plasma and packed cells and his INR was 1.45. Thereafter, his Hgb and INR (about 1.01) stabilized and hematomas were resolving by day 24. On day 28, he received low-molecular weight heparins. On day 30, he was discharged to a nursing home where he was to receive 6 months of warfarin therapy and close monitoring .
B) Warfarin potentiation by topical methyl salicylate ointment was demonstrated in a case report of a 61-year-old woman. The patient received warfarin (mean dose 4 to 5 milligrams daily) following mitral valve replacement. Subsequently, the patient used methyl salicylate ointment topically to relieve osteoarthritic pain. At a follow-up visit, the patient had a great number of bruises, an elevated INR (international normalized ratio) of 6.09, and a blood salicylate level of 2.5 mmol/L. The methyl salicylate ointment was discontinued, and the patient received 3 units of fresh frozen plasma and made an uneventful recovery .
C) A later report documented 11 patients who had elevated INRs and positive blood levels of salicylate. Elevated INRs and positive blood levels of salicylates were documented in 11 patients who had used a significant amount of topical methyl salicylate while receiving warfarin. Three patients had bleeding episodes, two had bruising, and one had gastrointestinal bleeding .
D) INR elevation was reported due to topical methyl salicylate 0.05% used by a 22-year-old female also taking warfarin. The patient had been using the topical product for 8 days for severe knee pain when she presented with bruising and bleeding gums; her INR was reported to be 12.2. The patient received oral vitamin K 2.5 mg, the next two doses of warfarin were withheld, and the topical methyl salicylate containing gel was discontinued. At the one-week follow up appointment, her INR was therapeutic and symptoms resolved .
E) One case report describes INR elevation due to topical methyl salicylate 0.05% used by a 68-year-old female also taking warfarin. The patient was being hospitalized for suspected recurrence of metastatic sarcoma and developed several complications including pulmonary embolus. The patient had been using the topical product for an unknown period of time for foot pain; her INR was reported unstable and out of the therapeutic range (2 to 4.5). The topical methyl salicylate containing oil was an Asian complementary preparation. The patient received oral vitamin K 10 mg twice during her hospital stay. She was discharged to a nursing home on warfarin 1 mg/day. The authors hypothesize that absorption of methyl salicylate from this topical preparation was sufficient to potentiate warfarin anticoagulation resulting in excessive INRs .
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.