Felodipine and Ketoconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole
Felodipine
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 felodipine exposure and additive negative inotropic effect
Interaction Deep Dive
Concomitant use of felodipine and ketoconazole is contraindicated as coadministration may result increased felodipine exposure with additive inotropic effects and an increased risk for edema and congestive heart failure5. Triazole antifungals (itraconazole, fluconazole) and imidazole antifungals (ketoconazole) inhibit hepatic isoenzyme CYP3A4, an enzyme involved in the metabolism of dihydropyridine calcium channel antagonists (NIFEdipine, niCARdipine, amLODIPine, isradipine, felodipine) 3. Literature reports have documented substantial peripheral edema and/or elevated calcium antagonist serum concentrations during concurrent use of itraconazole and felodipine, isradipine, or NIFEdipine 24.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of felodipine; additive negative inotropic effect
Literature reports
2 reports — tap to read
a) A 68-year-old woman experienced ankle edema following treatment with nifedipine and itraconazole. The patient had been administered atenolol and NIFEdipine for hypertension. She was then started on itraconazole for pedal onychomycosis. Ankle edema appeared after two to three days of itraconazole and resolved two to three days after itraconazole was discontinued. The ankle edema reappeared with each subsequent course of itraconazole except the final course. NIFEdipine trough concentrations were obtained with the last course of therapy. Relative to the itraconazole therapy, trough nifedipine concentrations were obtained four days prior to and three days during therapy. The mean NIFEdipine trough concentrations were 12.7 ng/mL and 56.1 ng/mL, respectively 1.
b) Peripheral edema and elevated serum felodipine levels were described in two patients receiving combined therapy with felodipine and itraconazole. Swelling of the lower extremities occurred in both cases within 3 to 7 days and resolved within 2 to 4 days following discontinuation of one of the agents. Re-challenge in one of the patients resulted in reoccurrence of the edema. In this patient, area under the felodipine plasma concentration-time curve (AUC) was found to be at least four times higher with itraconazole therapy. The authors also mention an additional patient who developed ankle swelling when itraconazole was added to isradipine therapy, however, further details were not supplied 2.
Common questions
Can I take Felodipine and Ketoconazole together?
Increased felodipine exposure and additive negative inotropic effect Always confirm with your pharmacist or prescriber before making any change.
How serious is the Felodipine and Ketoconazole interaction?
It is rated contraindicated. These should generally not be used together.
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.
Questions for your pharmacist
- Does my dose of Felodipine or Ketoconazole 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 (5)
- Tailor S, Gupta A, Walker S, et al: Peripheral edema due to nifedipine-itraconazole interaction: a case report. Arch Dermatol 1996; 132:350-352. DOI
- Neuvonen PJ & Suhonen R: Itraconazole interacts with felodipine. J Am Acad Dermatol 1995; 33:134-135. PubMed
- Gibaldi M: Drug interactions: part I. Ann Pharmacother 1992; 26:709-713. PubMed
- Tailor S, Gupta A, Walker S, et al: Peripheral edema due to nifedipine-itraconazole interaction: a case report. Arch Dermatol 1996; 132:350-352. DOI
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
Keep reading about Ketoconazole
Keep reading about Felodipine
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