Fluconazole significantly increases warfarin blood levels, dramatically raising the risk of bleeding. This interaction can cause INR values to spike to dangerous levels, leading to spontaneous bleeding, including intracranial hemorrhage. Even a short course of fluconazole can have a prolonged effect on warfarin levels.
How This Interaction Works (Mechanism)
Fluconazole is a potent inhibitor of CYP2C9, the primary enzyme responsible for metabolizing the more potent S-enantiomer of warfarin. Inhibition of CYP2C9 reduces warfarin clearance, causing its plasma concentration to rise significantly. Fluconazole also inhibits CYP3A4, which metabolizes the less potent R-enantiomer. The combined effect can increase INR by 2 to 3 times the baseline value within 2 to 5 days.
Source: American Society of Health-System Pharmacists Drug Interaction Monograph, 2025
When fluconazole is necessary for a patient on warfarin, reduce the warfarin dose by 25 to 50 percent prophylactically. Check INR within 3 to 5 days of starting fluconazole and adjust the warfarin dose accordingly. Continue frequent INR monitoring throughout fluconazole treatment and for 1 to 2 weeks after stopping it, as the enzyme inhibition persists. Report any signs of bleeding immediately.
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Sources and standards behind this page
What a drug interaction does, and how strongly it is supported, is documented in public labeling and federal safety references rather than in any one summary, and the sources below are the primary ones. They are linked so a reader can check a claim without taking this page's word for it.
- DailyMed carries the current FDA labeling for every marketed drug product, including the warnings and drug interaction sections.
- Drugs@FDA is the federal database of approved drug products and their approval documents.
- FDA: Drug interactions, what you should know explains how drug-drug, drug-food and drug-condition interactions are described on labels.
- FDA Drug Safety Communications publishes the agency's safety alerts and label changes as they are issued.
- FDA MedWatch is the program for reporting and reviewing adverse events, including suspected interactions.
- openFDA provides public access to FDA labeling and adverse event data.
- MedlinePlus drug information is the National Library of Medicine's consumer reference for what a medicine is and how it is taken.
- NIAAA: Harmful interactions documents which medicines interact with alcohol and how.
- NCCIH: Herb-drug interactions summarises the evidence on interactions between herbal products and medicines.
- National Library of Medicine maintains the drug and health databases the sources above draw on.
This page describes how this interaction works and where it is documented. It is not medical advice: a prescriber or pharmacist decides what applies to a particular patient and medication.
Frequently Asked Questions
Fluconazole and Warfarin have a severe interaction and should generally not be taken together without close medical supervision. The combination can cause serious, potentially life-threatening side effects. Contact your doctor immediately if you are currently taking both medications.
Fluconazole significantly increases warfarin blood levels, dramatically raising the risk of bleeding. This interaction can cause INR values to spike to dangerous levels, leading to spontaneous bleeding, including intracranial hemorrhage. Even a short course of fluconazole can have a prolonged effect on warfarin levels.
Yes. Anytime you are taking multiple medications, supplements, or substances, you should inform your doctor and pharmacist. They can evaluate your specific risk factors (age, kidney function, other medications, medical conditions) and determine whether the Fluconazole and Warfarin combination is safe for you, or whether adjustments are needed.
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