Fluconazole Drug Interactions

Introduction to Fluconazole Interactions

The American Heart Association recommends monitoring INR closely when initiating or discontinuing fluconazole in patients taking warfarin, as fluconazole can increase INR and bleeding risk through CYP2C9 inhibition, with a strength of evidence based on clinical studies 1
The Infectious Diseases Society of America suggests reducing cyclosporine doses by 30-50% in renal transplant patients taking fluconazole, due to significant increases in cyclosporine levels, with a moderate strength of evidence based on clinical trials 2

The American Heart Association advises reducing warfarin dose preemptively and monitoring INR every 2-3 days initially in patients taking warfarin and fluconazole, due to the increased risk of bleeding, with a high strength of evidence based on clinical studies 1
The Infectious Diseases Society of America recommends adjusting tacrolimus and sirolimus doses based on levels in patients taking these immunosuppressants with fluconazole, due to increased concentrations via CYP3A4 and P-glycoprotein inhibition, with a moderate strength of evidence based on clinical trials 2

The American College of Cardiology notes that statins, such as simvastatin, interact with fluconazole, carrying an increased risk of myopathy, with a moderate strength of evidence based on clinical trials 1, 3

The National Comprehensive Cancer Network (NCCN) notes that fluconazole can prolong the QT interval, and this risk is heightened when combined with fluoroquinolones, macrolides, or ondansetron. 4

The NCCN advises that patients receiving narrow‑therapeutic‑index medications metabolized by CYP2C9, CYP3A4, or CYP2C19 should be closely monitored for drug‑interaction effects when fluconazole is co‑administered. 5

The NCCN recommends obtaining infectious‑disease specialist consultation before initiating azole antifungal therapy in patients with complex polypharmacy. 4

According to the NCCN, fluconazole does not require therapeutic drug monitoring because of its linear pharmacokinetics, except in patients with renal impairment who require dose modification. 5