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.
Check More Drug Interactions
Use our free interaction checker to search thousands of drug, supplement, and food combinations.
Open Interaction CheckerSources and standards behind this page
Drug coverage in the United States is governed by published rules rather than by any one insurer's 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.
- FDA Orange Book publishes the therapeutic-equivalence ratings that decide whether a generic may be substituted for a brand-name drug.
- FDA generic drug facts sets out what "generic equivalent" means and what a manufacturer must prove.
- CMS prescription drug coverage defines the rules a Medicare drug plan formulary must follow and how it may change mid-year.
- Medicare.gov drug coverage (Part D) states what a Part D plan is required to offer a member.
- CMS prescription drug appeals documents the coverage-determination and exception process when a drug is denied.
- Medicare Plan Compare is the official tool for checking what a specific plan charges for a specific drug at a specific pharmacy.
- Drugs@FDA is the federal database of approved drug products, which establishes whether a covered product exists and in what form.
- DailyMed carries the current FDA labeling for every marketed drug product, including approved strengths and forms.
- MedlinePlus drug information is the National Library of Medicine's consumer reference for what a medication is and how it is used.
- FTC report on pharmacy benefit managers documents how the middlemen between an insurer and a pharmacy shape what a plan actually covers.
- National Library of Medicine maintains the drug and health databases the sources above draw on.
This page describes how coverage and formularies work. It is not medical advice, and a reader's own plan documents and prescriber decide what applies to them.
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.
Related Resources
- Supplement interactions with Fluconazole on Health Britannica
- Supplement interactions with Warfarin on Health Britannica
- Fluconazole prices and pharmacy comparison on RxGrab
- Warfarin prices and pharmacy comparison on RxGrab
- Full drug interaction checker tool
Get Drug Safety Alerts
Subscribe to receive updates on FDA warnings, new drug interactions, and patient safety information.