Cimetidine and Dofetilide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cimetidine
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 QT interval prolongation, and an increased risk of torsades de pointes
Interaction Deep Dive
Concurrent use of dofetilide and cimetidine is contraindicated as it may increase dofetilide exposure. If a patient is taking dofetilide and requires anti-ulcer therapy, use omeprazole, raNITIdine, antacids as alternatives to cimetidine, as these agents have no effect on the pharmacokinetics of dofetilide1. Cimetidine significantly increases dofetilide concentrations and QTc intervals by inhibiting dofetilide renal tubular secretion and metabolism through CYP3A4 2.
Why it happens (mechanism)
Renal cation inhibition; inhibition of CYP3A4-mediated metabolism of dofetilide
Literature reports
3 reports — tap to read
a) Cimetidine significantly increased dofetilide concentrations and QTc intervals in an open-label, placebo-controlled, randomized, four-way crossover study of 20 healthy subjects. Subjects received cimetidine 100 milligrams (mg), cimetidine 400 mg, raNITIdine 150 mg, or placebo twice daily for four days, with dofetilide 500 micrograms (mcg) administered on day 2. Cimetidine 100 mg and 400 mg increased the AUC of dofetilide by 11% and 48% and the Cmax by 11% and 29%, and decreased the renal clearance by 13% and 33%, respectively. Cimetidine 100 mg and 400 mg increased the QTc interval from baseline by 22% and 33%, respectively. RaNITIdine had no effect on dofetilide pharmacokinetics or pharmacodynamics 3.
b) Cimetidine significantly increases dofetilide concentrations and QTc intervals by inhibiting dofetilide renal tubular secretion and metabolism through CYP3A4 2.
c) Coadministration of cimetidine at 400 mg BID with dofetilide (500 mcg BID) for 7 days has been shown to increase dofetilide exposure by 58%. Cimetidine at doses of 100 mg BID resulted in a 13% increase in dofetilide exposure 1.
Common questions
Can I take Cimetidine and Dofetilide together?
Increased dofetilide exposure, 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 Cimetidine and Dofetilide 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 Cimetidine 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 (3)
- Product Information: Dofetilide oral capsules, dofetilide oral capsules. Granules Pharmaceuticals Inc. (per DailyMed), Chantilly, VA, 2025. 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
- Abel S, Nichols DJ, Brearley CJ, et al: Effect of cimetidine and ranitidine on pharmacokinetics and pharmacodynamics of a single dose of dofetilide. Br J Clin Pharmacol 2000; 49(1):64-71. PubMed
Keep reading about Cimetidine
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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