No Clinically Significant Interaction Between Jardiance and Fluconazole
Empagliflozin (Jardiance) does not have a clinically significant drug interaction with fluconazole, and the two medications can be co-administered without dose adjustment of either agent. 1
Evidence from FDA Labeling and Guidelines
The official FDA prescribing information for Jardiance does not list fluconazole as a contraindicated medication or one requiring special monitoring when used concurrently. 1 The drug interaction section of the Jardiance label specifically addresses interactions with diuretics, insulin/insulin secretagogues, and lithium, but makes no mention of azole antifungals including fluconazole. 1
Mechanistic Considerations
Empagliflozin Metabolism
- Empagliflozin is primarily metabolized through glucuronidation (UGT enzymes), not through the cytochrome P450 system. 2
- This insulin-independent mechanism of glucose lowering does not rely on hepatic CYP450 metabolism, making it less susceptible to drug interactions with CYP inhibitors. 2
Fluconazole's Interaction Profile
- Fluconazole is a known inhibitor of CYP2C9, CYP2C19, and to a lesser extent CYP3A4. 3, 4, 5
- However, fluconazole's CYP3A4 inhibition is much weaker compared to ketoconazole or itraconazole, and clinically significant interactions typically occur only at doses ≥200 mg/day. 5
- Since empagliflozin is not metabolized by these pathways, fluconazole's enzyme inhibition is not relevant. 2
Clinical Implications
You can safely prescribe both medications together without:
- Dose adjustments of either drug 1
- Additional monitoring beyond standard care for each medication 1
- Concerns about altered efficacy or increased toxicity 5
Important Caveats
While the empagliflozin-fluconazole combination is safe, be aware of:
- Genital mycotic infections: Empagliflozin increases the risk of genital fungal infections (a common adverse effect), which may paradoxically require antifungal treatment. 6, 1
- Volume depletion monitoring: Continue standard monitoring for empagliflozin's diuretic effects, especially if the patient is on other diuretics or has renal impairment. 1
- Hypoglycemia risk: If the patient is also taking insulin or sulfonylureas with empagliflozin, monitor for hypoglycemia regardless of fluconazole use. 1
Contrast with Other Azoles
Unlike itraconazole, ketoconazole, or voriconazole (which are potent CYP3A4 inhibitors and can cause significant interactions with many medications), fluconazole has a much more favorable interaction profile and does not interact with empagliflozin. 3, 7, 5