Glipizide and Fluconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fluconazole
Glipizide
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased glipiZIDE exposure and an increased risk of hypoglycemia
Interaction Deep Dive
Exert caution with concomitant use of fluconazole and glipiZIDE (CYP2C9 substrate that is an oral hypoglycemic agent) as it may precipitate clinically significant hypoglycemia due to reduced metabolism of glipiZIDE by fluconazole which may increase the exposure of glipiZIDE. When fluconazole is used concomitantly with glipiZIDE, blood glucose concentrations should be carefully monitored and the dose of the glipiZIDE should be adjusted as necessary. In three placebo-controlled studies in normal volunteers who received sulfonylurea alone as a single dose and again as a single dose following the administration of fluconazole 100 mg daily for 7 days, 22/46 (47.8%) of fluconazole-treated patients and 9/22 (40.1%) of placebo-treated patients experienced symptoms consistent with hypoglycemia. In 13 normal male volunteers, there was significant increase in glipiZIDE (2.5 mg single dose) AUC and Cmax following the administration of fluconazole. There was a mean +/- SD increase in glipiZIDE AUC of 49% (+/- 13%; range: 27% to 73%) and Cmax of 19% (+/- 23%; range: -11% to 79%). Fluconazole-mediated enzyme inhibition may persist for 4 to 5 days after discontinuation1.
Why it happens (mechanism)
Inhibition of CYP2C9-mediated metabolism of glipiZIDE
Literature reports
1 report — tap to read
a) In three placebo-controlled studies in normal volunteers who received sulfonylurea alone as a single dose and again as a single dose following the administration of fluconazole 100 mg daily for 7 days, 22/46 (47.8%) of fluconazole-treated patients and 9/22 (40.1%) of placebo-treated patients experienced symptoms consistent with hypoglycemia. In 13 normal male volunteers, there was significant increase in glipiZIDE (2.5 mg single dose) AUC and Cmax following the administration of fluconazole. There was a mean +/- SD increase in glipiZIDE AUC of 49% (+/- 13%; range: 27% to 73%) and Cmax of 19% (+/- 23%; range: -11% to 79%) 1.
Common questions
Can I take Glipizide and Fluconazole together?
Increased glipiZIDE exposure and an increased risk of hypoglycemia Always confirm with your pharmacist or prescriber before making any change.
How serious is the Glipizide and Fluconazole interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Glipizide or Fluconazole need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2024. DailyMed
Keep reading about Fluconazole
Keep reading about Glipizide
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist