Digoxin and Fluoxetine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Fluoxetine
Digoxin
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 digoxin exposure and an increased risk of digoxin toxicity (nausea, vomiting, arrhythmias)
Interaction Deep Dive
Coadministration of FLUoxetine to a patient taking another drug that is tightly bound to protein like digitoxin may cause a shift in plasma concentrations potentially resulting in an adverse effect since FLUoxetine is tightly bound to plasma proteins. The interaction between FLUoxetine and other highly protein-bound drugs has not been fully evaluated, but may be important1. One case report describes a 93-year-old female stabilized on digoxin who experienced toxic levels of digoxin after FLUoxetine had been added to her regimen for depression. Rechallenge with FLUoxetine again caused her digoxin levels to increase dramatically. While the mechanism of this interaction is not clear, it could be related to displacement of digoxin from binding sites or reduced clearance of digoxin 2.
Why it happens (mechanism)
Displacement of protein-bound FLUoxetine
Literature reports
2 reports — tap to read
a) Digoxin 0.125 mg daily was being administered to a 93-year-old female for congestive heart failure and paroxysmal atrial fibrillation. Digoxin levels ranged from 1.0 to 1.4 nmol/L during the two months preceding the initiation of FLUoxetine 10 mg daily. Within one week, the patient complained of anorexia. Her digoxin level measured 4.2 nmol/L, while renal function and potassium levels remained unchanged. Both digoxin and FLUoxetine were discontinued, and her digoxin level returned to normal in five days with resolution of the anorexia. During the next three weeks her digoxin serum levels ranged from 0.9 nmol/L to 1.4 nmol/L. Because the symptoms of depression persisted, FLUoxetine was again initiated at 10 mg daily and the digoxin serum level was closely monitored. After two days of FLUoxetine therapy, the digoxin level increased to 2.0 nmol/L, and after four days it was 2.8 nmol/L. Renal function remained unchanged, as did serum electrolytes. The patient again experienced anorexia, and treatment with FLUoxetine was discontinued 2.
b) The interaction between FLUoxetine and other highly protein-bound drugs has not been fully evaluated, but may be important 1.
Common questions
Can I take Digoxin and Fluoxetine together?
Increased digoxin exposure and an increased risk of digoxin toxicity (nausea, vomiting, arrhythmias) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Fluoxetine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 Digoxin or Fluoxetine 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 Fluoxetine
Keep reading about Digoxin
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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