Digoxin and Nefazodone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Nefazodone
No brand names on recordDigoxin
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
Interaction Deep Dive
Coadministration of digoxin and nefazodone (P-gp inhibitor) may increase digoxin exposure. Measure digoxin exposure prior to initiation of concurrent use. Reduce digoxin concentrations by reducing the digoxin dose (by approximately 15% to 30% with oral preparations) or by modifying the dosing frequency. Continue monitoring digoxin exposure. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing nefazodone12.
Why it happens (mechanism)
Inhibition of P-gp mediated efflux transport of digoxin
Literature reports
2 reports — tap to read
a) In pharmacokinetic studies, coadministration of digoxin and nefazodone resulted in a 27% increase in digoxin serum concentrations and a 15% increase in digoxin AUC 12.
b) To assess the effect of nefazodone on the pharmacokinetic and pharmacodynamic parameters of digoxin, 18 healthy male volunteers participated in an open, randomized, multiple-dose, three-way crossover study. Volunteers received nefazodone 200 mg twice daily, digoxin 0.2 mg daily, or both during three 8-day treatment periods, with a 10-day washout period in between treatment periods. Steady-state AUC, Cmax, and Cmin concentrations of digoxin were increased by 15%, 29% and 27%, respectively. No significant changes were observed in vital signs, heart rate, or PR, QRS, and QT intervals. Because digoxin has a narrow therapeutic index, monitoring of levels and an adjustment of the digoxin dose may be necessary when given concurrently with nefazodone 3.
Common questions
Can I take Digoxin and Nefazodone together?
Increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Nefazodone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Digoxin or Nefazodone 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: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
- Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. 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
Keep reading about Nefazodone
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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