Cyclobenzaprine and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclobenzaprine
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
An increased risk of QT interval prolongation
Interaction Deep Dive
Coadministration of cyclobenzaprine with another QT prolonging drug may result in additive QT prolongation12. In a case report, the combination of FLUoxetine and cyclobenzaprine was suspected to have caused asymptomatic QT interval prolongation in a female patient, which progressed to torsade de pointes and ventricular fibrillation after preoperative administration of droPERidol, a drug known to prolong the QT interval and cause torsade de pointes 2.
Why it happens (mechanism)
Additive QT interval prolongation
Literature reports
1 report — tap to read
a) A 59-year-old woman developed torsade de pointes, progressing to ventricular fibrillation and cardiac arrest, after receiving droPERidol during elective Achilles tendon surgery the day after discontinuing cyclobenzaprine. Five days prior to the surgery, her QTc was prolonged at 497 milliseconds (msec); magnesium and potassium were within normal limits. Her home medication regimen, which was discontinued the day prior to surgery, included cyclobenzaprine 10 mg/day and FLUoxetine 30 mg/day, as well as amLODIPine, diclofenac, and triamterene/hydroCHLOROthiazide. She was premedicated 45 minutes prior to surgery with droPERidol 0.625 mg IV and metoclopramide 10 mg IV. Approximately 1 hour and 45 minutes after the surgery had started, the patient developed ventricular tachycardia consistent with torsade de pointes which progressed into ventricular fibrillation and cardiac arrest. Immediately following cardioversion, the patient's QTc was 500 msec with no evidence of ischemic injury. On postoperative day 1, her QT interval had normalized to 440 msec, which was below her baseline value, and an ECG showed normal sinus rhythm. The patient had no known history of cardiac disease or evidence of risk factors associated with torsade de pointes or other dysrhythmias. All preadmission medications were restarted at discharge, with the exception of cyclobenzaprine 2.
Common questions
Can I take Cyclobenzaprine and Ketoconazole Topical together?
An increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclobenzaprine and Ketoconazole Topical 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Cyclobenzaprine or Ketoconazole Topical 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: TONMYA(TM) sublingual tablets, cyclobenzaprine HCl sublingual tablets. Tonix Pharmaceuticals, Inc (per manufacturer), Chatham, NJ, 2025. DailyMed
- Michalets EL, Smith LK, & Van Tassel ED: Torsade de Pointes resulting from the addition of droperidol to an existing cytochrome P450 drug interaction. Ann Pharmacother 1998; 32:761-765. PubMed
Keep reading about Cyclobenzaprine
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.
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