Ketoconazole Topical and Imipramine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Imipramine
No brand names on recordKetoconazole Topical
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 QT interval prolongation, reduced clearance and prolonged half-life of imipramine
Interaction Deep Dive
Coadministering oral ketoconazole and a drug that are known to prolong the QT interval, such as may increase the risk of QT interval prolongation1. In a controlled study of six healthy volunteers, coadministration of ketoconazole with a single dose of imipramine resulted in an increase in imipramine area under the concentration-time curve (AUC) and imipramine half-life as well as a decrease in imipramine clearance. The changes were minor, however, and deemed to be likely clinically insignificant considering the wide therapeutic range of imipramine 2.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of imipramine hepatic metabolism
Literature reports
1 report — tap to read
a) A controlled study evaluated oral ketoconazole and the pharmacokinetic effects on oral imipramine and desipramine in 12 healthy male volunteers. The subjects were divided into two groups and received either a single dose of imipramine 100 mg or desipramine 100 mg, both alone and after 10 days of a 14-day regimen of oral ketoconazole 200 mg per day. Coadministration of ketoconazole resulted in significantly increased imipramine area under the concentration-time curve (AUC) values (from 3795 +/- 918 nmol h/L to 4567 +/- 1076 nmol h/L) and significantly decreased imipramine oral clearance (from 1.16 +/- 0.21 L/hr/kg to 0.96 +/- 0.20 L/hr/kg). Imipramine half-life was also significantly increased during coadministration with ketoconazole, from 16.7 +/- 3.3 hours to 19.2 +/- 5.4 hours. The changes in imipramine pharmacokinetics were deemed to be minor considering the therapeutic range of the drug. During coadministration of ketoconazole with desipramine, no significant pharmacokinetic changes were observed. The authors concluded that ketoconazole inhibits the N-demethylation of imipramine by cytochrome P450 3A4, without affecting the 2-hydroxylation of imipramine and desipramine, which is thought to be mediated through the cytochrome P450 2D6 pathway 2.
Common questions
Can I take Ketoconazole Topical and Imipramine together?
Increased risk of QT interval prolongation, reduced clearance and prolonged half-life of imipramine Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Imipramine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
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 Ketoconazole Topical or Imipramine 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: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Spina E, Avenoso A, Campo GM, et al: Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects. Br J Clin Pharmacol 1997; 43:315-318. PubMed
Keep reading about Imipramine
Keep reading about Ketoconazole Topical
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