Dofetilide and Ketoconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole
Dofetilide
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 dofetilide exposure, an increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest) and an increased risk of QT interval prolongation
Interaction Deep Dive
Ketoconazole increased dofetilide exposure through inhibition of CYP3A4 and renal tubular secretion of dofetilide; concomitant use is contraindicated31. Elevated serum levels of dofetilide have been associated with serious cardiovascular events, including QT prolongation, torsades de pointes, ventricular tachycardia, cardiac arrest, and sudden death 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated dofetilide metabolism; inhibition of renal cation transport system; additive QT interval prolongation
Literature reports
2 reports — tap to read
a) The coadministration of ketoconazole 400 mg daily and dofetilide 500 mcg twice daily for seven days increased the dofetilide Cmax by 53% and 97% in males and females, respectively, and increased the dofetilide AUC by 41% in males and 69% in females 1.
b) Ketoconazole increases dofetilide exposure through inhibition of both CYP3A4 and the renal cation transport system. Drugs that inhibit tubular secretion through the renal cation transport system are contraindicated with dofetilide. In addition, ketoconazole has been associated with QT prolongation 3.
Common questions
Can I take Dofetilide and Ketoconazole together?
Increased dofetilide exposure, an increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest) and an increased risk of QT interval prolongation Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dofetilide and Ketoconazole interaction?
It is rated contraindicated. These should generally not be used together.
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 "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Dofetilide or Ketoconazole 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: TIKOSYN(R) oral capsules, dofetilide oral capsules. Pfizer Labs (per FDA), New York, NY, 2019. DailyMed
- Allen MJ, Oliver SD, Newgreen MW, et al: Pharmacodynamic effect of continuous vs intermittent dosing of dofetilide on QT interval. Br J Clin Pharmacol 2002; 53:59-65.
- Yamreudeewong W, DeBisschop M, Martin LG, et al: Potentially significant drug interactions of class III antiarrhythmic drugs. Drug Safety 2003; 26(6):421-438. PubMed
Keep reading about Ketoconazole
Keep reading about Dofetilide
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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