Bretylium and Dofetilide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Dofetilide
Bretylium
No brand names on record
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 cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest)
Interaction Deep Dive
Concomitant use of two Class III antiarrhythmic agents may cause additive effects on the QT interval and is not recommended2. Cases of QTc prolongation and/or torsades de pointes have been reported with all Class III antiarrhythmic agents, including acecainide 3, amiodarone 4, azimilide 5, ibutilide 6, sematilide 7, dofetilide 1, and tedisamil 8. Class III antiarrhythmic drugs should not be administered concomitantly with or within four hours postinfusion of ibutilide 9. It is recommended that Class III antiarrhythmic agents be withheld for at least 3 half-lives before initiating dofetilide, and 5 half-lives before and 4 hours after ibutilide is administered. Dofetilide should be stopped for at least 2 days before any interacting drug is initiated 2.
Why it happens (mechanism)
Additive effect on QT prolongation
Literature reports
1 report — tap to read
a) All class III antiarrhythmic agents can prolong the QTc interval. Concurrent use of more than one class III antiarrhythmic agent is not recommended. It is recommended that class III antiarrhythmic agents be withheld for 3 half-lives before dofetilide is initiated, and 5 half-lives before and 4 hours after ibutilide is administered. Dofetilide should be stopped for at least 2 days before any interacting drug is initiated. If concurrent use cannot be avoided, cautious dosing and telemetric monitoring is advised 2.
Common questions
Can I take Bretylium and Dofetilide together?
An increased risk of cardiotoxicity (QT interval prolongation, torsades de pointes, cardiac arrest) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Bretylium and Dofetilide 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 "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 Bretylium or Dofetilide 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 (9)
- 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
- Chow MJ, Piergies AA, Bowsher DJ, et al: Torsade de pointes induced by N-acetylprocainamide. J Am Coll Cardiol 1984; 4:621-624. DOI
- Faggiano P, Gardini A, D'Aloia A, et al: Torsade de pointes occurring early during oral amiodarone treatment. Int J Cardiol 1996; 55(2):205-208. PubMed
- Corey AE, Agnew JR, Valentine SN, et al: Azimilide pharmacokinetics following intravenous and oral administration of a solution and capsule formulation. J Clin Pharmacol 1999; 39(12):1272-1276. PubMed
- Rodriguez I, Kilborn MJ, Liu XK, et al: Drug-induced QT prolongation in women during the menstrual cycle. JAMA 2001; 285(10):1322-1326. PubMed
- Singh BN: The coming of age of the class III antiarrhythmic principle: retrospective and future trends. Am J Cardiol 1996; 78(suppl):17-27. DOI
- Bargheer K, Bode F, Klein HU, et al: Prolongation of monophasic action potential duration and the refractory period in the human heart by tedisamil, a new potassium-blocking agent. Eur Heart J 1994; 15:1409-1414. DOI
- Product Information: Corvert(R), ibutilide fumarate injection. Upjohn Company, Kalamazoo, MI, 1998. DailyMed
Keep reading about Dofetilide
Keep reading about Bretylium
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