Ketoconazole Topical and Reboxetine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Reboxetine
No brand names on record
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 reboxetine bioavailability
Interaction Deep Dive
Avoid concomitant use of reboxetine with strong CYP3A4 inhibitors, as coadministration may result in increased reboxetine plasma concentrations. When reboxetine and the strong CYP3A4 inhibitor, ketoconazole, were used concurrently, plasma concentrations of reboxetine enantiomers increased by approximately 50%1, although no apparent effect on vital signs or the side effect profile was seen 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated reboxetine metabolism
Literature reports
1 report — tap to read
a) Eleven healthy volunteers participated in a single-dose, open-label, randomized study to assess the extent to which ketoconazole decreases the clearance of reboxetine. Each subject was given ketoconazole 200 mg once daily on days 1 through 5 and reboxetine 4 mg on day 2, or reboxetine 4 mg on day 2 in a crossover fashion. For the R,R- enantiomer of reboxetine, ketoconazole increased the mean area under the concentration-time curve (AUC) by 58% (from 1726 ng/h/mL to 2730 ng/h/mL), decreased the oral clearance by 34% (from 41.6 mL/min to 27.5 mL/min), and increased the half-life from 14.8 hours to 21.5 hours. The AUC value for the S,S- enantiomer of reboxetine was increased by 43% (from 762 ng/h/mL to 1090 ng/h/mL), the oral clearance was decreased by 24% (from 99.3 mL/min to 75.6 mL/min), and the half-life was prolonged from 14.4 hours to 18.9 hours in the presence of ketoconazole. Peak plasma concentrations of reboxetine were not significantly altered, which coincided with the lack of any relevant changes in blood pressure, heart rate, temperature, respirations, or hematologic parameters 2.
Common questions
Can I take Ketoconazole Topical and Reboxetine together?
Increased reboxetine bioavailability Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Reboxetine 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Reboxetine 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 (2)
- Product Information: EDRONAX oral tablets, reboxetine oral tablets. Pfizer Limited (per MHRA), Sandwich, Kent, United Kingdom, 2015.
- Herman BD, Fleishaker JC, & Brown MT: Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in humans. Clin Pharmacol Ther 1999; 66:374-379.
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Keep reading about Reboxetine
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