Digoxin and Trazodone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Trazodone
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
Concomitant use of traZODone and digoxin may increase digoxin exposure. Measure serum digoxin exposure before initiating concomitant use of traZODone. Continue monitoring and reduce digoxin dose as necessary1. Digoxin maximum serum concentrations were increased nearly 30% compared with baseline after nefazodone (an antidepressant structurally related to traZODone) was given concurrently, in an open, randomized, crossover interaction study 2. Digoxin toxicity occurred in a 68-year-old woman after traZODone was added to a stable treatment regimen that included digoxin. Her digoxin level had remained within a stable therapeutic range for many months prior to beginning traZODone therapy 3. Increased serum digoxin serum concentrations have also been reported in patients treated concurrently with traZODone and digoxin 5.
Why it happens (mechanism)
Unknown
Literature reports
3 reports — tap to read
a) Digoxin serum concentrations were increased nearly 30% compared with baseline after nefazodone (a phenylpiperazine antidepressant structurally related to traZODone) was given concurrently with digoxin. In an open, randomized, triple-crossover interaction study, healthy subjects (n=18) received an 8-day oral regimen of digoxin 0.2 milligrams (mg) daily, nefazodone 200 mg twice daily, or both drugs administered concomitantly during each 8-day trial period; all subjects crossed over to an alternate study regimen after a 10-day wash-out period. Steady-state area under the AUC and Cmax and Cmin digoxin exposure were increased by 15%, 29% and 27%, respectively (p less than 0.05, each parameter). No significant changes were observed in vital signs, heart rate, or PR, QRS, and QT intervals. The frequency and severity of adverse events did not differ between treatment groups 2.
b) Digoxin toxicity occurred in a 68-year-old woman after traZODone was added to a stable treatment regimen that included digoxin. Prior to beginning traZODone therapy, her serum digoxin level had remained within therapeutic range for many months (at a dose of digoxin 125 micrograms (mcg) daily), and on admission was 0.8 nanograms/mL (1 nanomol/L). She was hospitalized for severe depression; traZODone was initiated at a dose of 50 milligrams (mg) on day 1, and then escalated to 300 mg daily by day 11. On treatment day 14, the patient complained of nausea and vomiting; her digoxin level measured at 2.8 nanograms/mL (3.6 nanomol/L). TraZODone 300 mg daily was continued and digoxin was withdrawn until therapeutic digoxin serum levels were restored. The patient's digoxin levels were sustained within therapeutic range after conversion to an every-other-day regimen of digoxin 125 mcg while she continued to receive traZODone 300 mg daily 3.
c) Increased serum concentrations of digoxin have been observed in patients receiving concurrent treatment with traZODone 4.
Common questions
Can I take Digoxin and Trazodone 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 Trazodone 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 Trazodone 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 (5)
- Product Information: Trazodone HCl oral tablets, trazodone HCl oral tablets. Rising Pharma Holdings, Inc (per DailyMed), East Brunswick, NJ, 2025. DailyMed
- Dockens RC, Greene DS, & Barbhaiya RH: Assessment of pharmacokinetic and pharmacodynamic drug interactions between nefazodone and digoxin in healthy male volunteers. J Clin Pharmacol 1996; 36:160-167. PubMed
- Rauch PK & Jenike MA: Digoxin toxicity possibly precipitated by trazodone. Psychosomatics 1984; 25(4):334-335. DOI
- Product Information: Desyrel(R), trazodone HCL. Bristol-Myers Squibb Company, Princeton, NJ, 2003. DailyMed
- Product Information: Desyrel(R), trazodone HCL. Bristol-Myers Squibb Company, Princeton, NJ, 2003. DailyMed
Keep reading about Trazodone
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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