Hydrochlorothiazide and Dofetilide: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Hydrochlorothiazide
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 hypokalemia or hypomagnesemia, an increased risk of QT interval prolongation, and an increased risk of torsades de pointes
Interaction Deep Dive
The concomitant use of dofetilide and hydroCHLOROthiazide is contraindicated as it may increase dofetilide exposure and may also increase the risk of QT interval prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting diuretics, increasing the potential for torsade de pointes. Potassium levels should be within the normal range prior to administration of dofetilide and maintained in the normal range during administration of dofetilide1.
Why it happens (mechanism)
Unknown
Literature reports
2 reports — tap to read
a) Concomitant use of hydroCHLOROthiazide 50 mg QD or hydroCHLOROthiazide/triamterene 50/100 mg QD with dofetilide 500 mg QD for 5 days resulted in increase in dofetilide AUC and Cmax by 27% and 21%, respectively in patients receiving hydroCHLOROthiazide alone. In patients receiving hydroCHLOROthiazide in combination with triamterene, dofetilide AUC and Cmax increased by 30% and 16%, respectively 1.
b) In a study patients received a 5-day regimen of either 50 mg hydroCHLOROthiazide once daily with 500 mcg dofetilide twice daily or 50/100 mg hydroCHLOROthiazide/triamterene once daily with dofetilide 500 mcg twice daily. This regimen followed 2 days of the respective diuretic at half dose. In those patients who received hydroCHLOROthiazide alone, the dofetilide AUC increased by 27% and Cmax increased by 21%. However, there was a large increase in the pharmacodynamic effects as measured by QTc increase over time and maximum QTc increase. The observed increases were 197% and 95%, respectively. In patients receiving the combination of hydroCHLOROthiazide and triamterene the dofetilide AUC increased by 30%, the Cmax increased by 16%, the QTc increase over time increased by 190% and the maximum QTc increased by 84% 2.
Common questions
Can I take Hydrochlorothiazide and Dofetilide together?
Increased dofetilide exposure, an increased risk of hypokalemia or hypomagnesemia, 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 Hydrochlorothiazide 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 Hydrochlorothiazide 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 (2)
Keep reading about Hydrochlorothiazide
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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