Nitrofurantoin and Fluconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fluconazole
Nitrofurantoin
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 risk of hepatic and pulmonary toxicity
Interaction Deep Dive
Pulmonary and hepatic toxicity developed in a 73-year-old man after fluconazole was added to a prolonged treatment regimen of nitrofurantoin. He had previously received 3 months of concomitant treatment with itraconazole 400 mg/day (for 7 days each month) and nitrofurantoin without incident1.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) Pulmonary and hepatic toxicity developed in a 73-year-old man after fluconazole was added to a prolonged treatment regimen of nitrofurantoin. The patient had been treated over the preceding 5 years with nitrofurantoin 50 milligrams (mg)/day prior to beginning a regimen of fluconazole 150 mg per week for treatment of onychomycosis. Two years prior to presentation, he had received 3 months of treatment with itraconazole 400 mg/day (for 7 days each month) without incident. Two months after beginning fluconazole therapy, the patient presented with complaints of fatigue, dyspnea on exertion, pleuritic-type pain accompanied by a burning tracheal pain, and a worsening, mildly productive cough. Chest radiography confirmed the presence of bilateral pulmonary disease that appeared consistent with nitrofurantoin pulmonary toxicity. Laboratory blood analysis revealed clinically significant elevations over baseline in aspartate and alanine aminotransferase serum concentrations (from 64 Units/Liter (U/L) to 223 U/L and from 54 U/L to 297 U/L, respectively). Nitrofurantoin and fluconazole were discontinued, after which the patient's symptoms and laboratory abnormalities slowly resolved 1.
Common questions
Can I take Nitrofurantoin and Fluconazole together?
Increased risk of hepatic and pulmonary toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nitrofurantoin 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 "delayed". Effects tend to build up gradually over days to weeks.
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 Nitrofurantoin 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)
- Linnebur SA & Parnes BL: Pulmonary and hepatic toxicity due to nitrofurantoin and fluconazole treatment. Ann Pharmacother 2004; 38:612-616. PubMed
Keep reading about Fluconazole
Keep reading about Nitrofurantoin
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.
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