Ketoconazole Topical and Risperidone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Risperidone
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 risperiDONE exposure and an increased risk of QT interval prolongation
Interaction Deep Dive
Caution is warranted with the concurrent use of risperiDONE and ketoconazole1. The concomitant use of ketoconazole with risperiDONE may result in increased adverse effects of risperiDONE due to an increase in systemic exposure of risperiDONE. A pharmacokinetic study of 10 healthy, nonsmoking adult males demonstrated that concurrent use of ketoconazole and risperiDONE decreased the clearance of risperiDONE by approximately 35%, increased the AUC by 67%, and prolonged the t(1/2) by 28% due to the inhibition of CYP3A4-mediated risperiDONE metabolism by ketoconazole. Monitoring for clinical effect and adverse events as a result of increased risperiDONE exposure is recommended 2. In addition, both ketoconazole and risperiDONE have been shown prolong the QT interval 3 and result in life-threatening ventricular tachyarrhythmias such as torsade de pointes. Hence reduce risperiDONE dose as deemed necessary 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of risperiDONE; additive QT interval prolongation
Literature reports
1 report — tap to read
a) Concomitant use of ketoconazole and risperiDONE significantly decreased the clearance, raised the AUC, and prolonged the elimination half-life of risperiDONE in a randomized, open-label, pharmacokinetic, crossover study of 10 healthy, nonsmoking adult males. The study involved 2 periods separated by a 2-week washout period: in period 1, each subject received a single dose of risperiDONE 2 mg and in period 2, each subject received a single dose of risperiDONE 2 mg after pretreatment with ketoconazole 200 mg once daily for 3 days. The AUC(0 to infinity) in the risperiDONE treatment group was 73.19 +/- 46.36 nanograms (ng) x hr/mL compared with 113.71 +/- 63.32 ng x hr/mL in the ketoconazole/risperiDONE group (p less than 0.001). The t(1/2) was 4.87 +/- 3.23 hours and 6.46 +/- 5.32 hours, respectively (p less than 0.05). The clearance of risperiDONE significantly decreased by 34.81% +/- 15.1% (p less than 0.05) and the apparent Vd increased by 39.79% +/- 53.39% (p less than 0.001) after the coadministration with ketoconazole 2.
Common questions
Can I take Ketoconazole Topical and Risperidone together?
Increased risperiDONE exposure and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Risperidone 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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Risperidone 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
- Mahatthanatrakul W, Sriwiriyajan S, Ridtitid W, et al: Effect of cytochrome P450 3A4 inhibitor ketoconazole on risperidone pharmacokinetics in healthy volunteers. J Clin Pharm Ther 2012; 37(2):221-225. PubMed
- Product Information: RISPERDAL(R) oral tablets, oral solution, risperidone oral tablets, oral solution. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2022. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Risperidone
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