Trimethoprim and Dofetilide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Dofetilide
Trimethoprim
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 and an increased risk of QT interval prolongation, and an increased risk of torsades de pointes
Interaction Deep Dive
Trimethoprim inhibits the renal tubular secretion of dofetilide; concomitant use of trimethoprim and dofetilide is contraindicated41 as it may increase dofetilide exposure 2.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of renal tubular secretion of dofetilide
Literature reports
2 reports — tap to read
a) Trimethoprim 160 mg in combination with sulfamethoxazole 800 mg coadministered twice daily with dofetilide 500 mcg twice daily for four days resulted in an increase in the dofetilide AUC by 103% and a 93% increase in the Cmax. Dofetilide can cause serious ventricular arrhythmias associated with QT interval prolongation, including torsades de pointes, which are directly related to the dofetilide plasma concentration 3.
b) Trimethoprim inhibits the renal tubular secretion of dofetilide; concomitant use of trimethoprim and dofetilide is contraindicated 41.
Common questions
Can I take Trimethoprim and Dofetilide together?
Increased dofetilide exposure and an increased risk of QT interval prolongation, and an increased risk of torsades de pointes Always confirm with your pharmacist or prescriber before making any change.
How serious is the Trimethoprim and Dofetilide interaction?
It is rated contraindicated. These should generally not be used together.
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 "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 Trimethoprim 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 (4)
- Allen MJ, Nichols DJ, & Oliver SD: The pharmacokinetics and pharmacodynamics of oral dofetilide after twice daily and three times daily dosing. Br J Clin Pharmacol 2000; 50:247-253. PubMed
- Product Information: Dofetilide oral capsules, dofetilide oral capsules. Granules Pharmaceuticals Inc. (per DailyMed), Chantilly, VA, 2025. DailyMed
- Product Information: Tikosyn(TM), dofetilide capsules. Pfizer Inc, New York, NY, 1999. DailyMed
- 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 Dofetilide
Keep reading about Trimethoprim
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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