Ketoconazole Topical and Tolterodine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tolterodine
Ketoconazole 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
Enhanced tolterodine bioavailability in individuals with deficient CYP2D6 activity; increased risk for QT interval prolongation
Interaction Deep Dive
Coadministration of ketoconazole, a strong CYP3A4 inhibitor that prolong QT interval and tolterodine, a CYP3A4 substrate that are known to prolong the QT interval is contraindicated1, as it may increase the risk of serious ventricular arrhythmias including torsades de pointes. In addition, concomitant use may result in enhanced tolterodine bioavailability in individuals with deficient CYP2D6 activity. If concomitant use is required, it is recommended that the dose of tolterodine be decreased to 1 mg twice daily or 2 mg once a day (long-acting formulation) 2. Tolterodine is metabolized via hydroxylation catalyzed by CYP2D6 and via N-dealkylation catalyzed by CYP3A4. The high CYP2D6 specificity of tolterodine suggests that extensive metabolizers are not likely to be affected by the coadministration of a CYP3A4 inhibitor. However, in subjects deficient in CYP2D6, the oral clearance of tolterodine decreased by 60% when ketoconazole, a potent CYP3A4 inhibitor, was coadministered 3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of tolterodine; additive QT interval prolongation
Literature reports
1 report — tap to read
a) Eight healthy volunteers, all deficient in CYP2D6 activity, received single and multiple doses of tolterodine in the presence and absence of ketoconazole during an open, non-randomized, crossover study. During the single-dose study, subjects were given ketoconazole 200 mg once daily for four days, with a 2 mg dose of tolterodine being coadministered on day 2. Tolterodine was given as 1 mg twice daily for 4.5 days during the multiple-dose study. The pharmacokinetic values obtained after the multiple-dose study were similar to those seen after the single-dose study during the ketoconazole phase. The Cmax of tolterodine increased approximately 2-fold in the presence of ketoconazole, with no effect on the time to Cmax. The apparent oral clearance of tolterodine decreased by 60% during ketoconazole coadministration, with a subsequent 2.5-fold increase in the area under the concentration-time curve (AUC). This study demonstrated that CYP3A4 catalyzed the N-dealkylation of tolterodine in poor metabolizers of CYP2D6 3.
Common questions
Can I take Ketoconazole Topical and Tolterodine together?
Enhanced tolterodine bioavailability in individuals with deficient CYP2D6 activity; increased risk for QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Tolterodine interaction?
It is rated contraindicated. These should generally not be used together.
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 Tolterodine 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 (3)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: Detrol(R) oral tablets, tolterodine tartrate oral tablets. Pharmacia & Upjohn Co (per FDA), New York, NY, 2012. DailyMed
- Brynne N, Forslund C, Hallen B, et al: Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity. Br J Clin Pharmacol 1999; 48:564-572. PubMed
Keep reading about Tolterodine
Keep reading about Ketoconazole Topical
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