Warfarin with Voriconazole Interaction Details
Brand Names Associated with Warfarin
- Coumadin®
- Jantoven®
- Warfarin
Brand Names Associated with Voriconazole
- Vfend®
- Voriconazole
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 07, 2023
Interaction Effect
An increased risk of bleeding
Interaction Summary
Voriconazole is a CYP2C9 substrate and inhibitor and concomitant use with anticoagulants metabolized via CYP2C9, such as warfarin, may result in increased INR and increased risk for bleeding . In one study, coadministration of voriconazole (300 mg every 12 hours for 12 days) with warfarin (single 30-mg dose) significantly increased the maximum prothrombin time by approximately 2 times that of placebo in healthy subjects . The suspected mechanism of interaction may also involve alterations in intestinal flora that synthesize vitamin K. In a nested case-control study of continuous warfarin users aged 65 years or older, there was 2-fold increase in risk of bleeding requiring hospitalization with exposure to any antibiotic, specifically a 4.5-fold increase with azole antifungals, including voriconazole. When possible, substitute voriconazole with an antifungal with a low-risk profile for bleeding in patients on stable anticoagulation therapy . If concomitant use of voriconazole is required in patients receiving oral anticoagulants such as warfarin, close monitoring of prothrombin time and other appropriate anticoagulation tests are recommended .
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Concomitant use of voriconazole and an anticoagulant should be approached with caution, as coadministration with warfarin resulted in an increased INR and increased risk for bleeding. When possible, substitute voriconazole with an antifungal with a low-risk profile for bleeding in patients on stable anticoagulation therapy. If concomitant use of voriconazole and a coumarin anticoagulant is required, monitor prothrombin time or other suitable anticoagulation tests at close intervals and adjust the dosage of anticoagulants accordingly .
Mechanism Of Interaction
Disruption of vitamin K synthesis; inhibition of CYP2C9-mediated metabolism by voriconazole
Literature Reports
A) Initiation of antibiotics in patients on continuous warfarin therapy resulted in a significantly increased risk of serious bleeding requiring hospitalization according to a nested case-control study of United States Medicare part D beneficiaries aged 65 years and older (n=38,762). Patients on warfarin who received any antibiotic were twice as likely to be hospitalized for bleeding compared with matched controls on warfarin who were not exposed to antibiotics (adjusted odds ratio (aOR), 2.01; 95% CI, 1.62 to 2.5). Additionally, continuous-warfarin users were twice as likely to have a bleeding event that required hospitalization within 60 days of antibiotic exposure compared with non-exposure. Antibiotic exposure greater than 60 days from the index bleed was not significantly associated with increased risk of bleeding. Specific antibiotics with the highest bleeding risk were azole antifungals (aOR, 4.57; 95% CI, 1.9 to 11.03), followed by cotrimoxazole (aOR, 2.7; 95% CI, 1.46 to 5.05), cephalosporins (aOR, 2.45; 95% CI, 1.52 to 3.95), penicillins (aOR, 1.92; 95% CI, 1.21 to 2.07), macrolides (aOR, 1.86; 95% CI, 1.08 to 3.21), and quinolones (aOR, 1.69; 95% CI, 1.09 to 2.62) .
B) Prothrombin time increased significantly, with 6 reported bleeding events, in 16 warfarin-treated patients that were randomized to receive voriconazole in a double-blind, placebo-controlled, 2-way crossover trial. Healthy men were randomized to receive voriconazole 300 mg or placebo, twice daily for 12 days plus a single dose of 30 mg of warfarin on day 7 of each study period. Study periods were separated by a 7-day washout. Four cases of hemorrhage were reported with voriconazole plus warfarin compared to none reported with placebo plus warfarin. Two cases of gum hemorrhage were reported with voriconazole plus warfarin compared to one case with placebo with warfarin. There were significant differences in area under the effect curve (AUEC) (3211 s-h vs 2282 s-h, p=0.0002) and mean maximum increase from baseline in prothrombin time (17 seconds vs 8 seconds, p=0.0004) between the voriconazole treatment period and placebo treatment period, respectively .
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.
Voriconazole Overview
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Voriconazole is used in adults and children 2 years of age and older to treat serious fungal infections such as invasive aspergillosis (a fungal infection that begins in the lungs and spreads through the bloodstream to other organs), esophageal candidiasis (a yeast [a type of fungus] infection that may cause white patching in the mouth and throat), and candidemia (a fungal infection in the blood). It is also used to treat certain other fungal infections when other medications will not work for certain patients. Voriconazole is in a class of antifungal medications called triazoles. It works by slowing the growth of the fungi that cause infection.
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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.