Digoxin and Propafenone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Digoxin
Propafenone
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 propafenone (P-gp inhibitor) may increase digoxin exposure. Measure digoxin exposure before initiating concomitant drugs. Reduce digoxin concentrations by decreasing dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring12. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring 43. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing propafenone 3.
Why it happens (mechanism)
Inhibition of P-gp mediated efflux transport of digoxin
Literature reports
2 reports — tap to read
a) During pharmacokinetic studies, coadministration of oral digoxin and propafenone resulted in a 60% to 270% increase in digoxin AUC 12. Similarly, coadministration of IV/IM digoxin and propafenone resulted in a 28% increase in digoxin serum concentrations and a 29% increase in digoxin AUC 43.
b) Concomitant administration of oral propafenone and intravenous digoxin resulted in an increase in the area under the plasma concentration-time curve (AUC) and a decrease in the clearance of digoxin. In this study, six male volunteers were administered intravenous digoxin 1 mg alone, then the same dose after pretreatment with propafenone 150 mg orally every eight hours for seven days; intravenous digoxin 1 mg was also administered after propafenone 300 mg orally every eight hours for seven days. The total body clearance of digoxin decreased in a dose-related fashion, from 2.45 mL/min/kg on digoxin alone to 2.17 mL/min/kg after pretreatment with the lower dose of propafenone for seven days, and then to 1.92 mL/min/kg after pretreatment with the higher dose of propafenone. Propafenone serum levels increased by 2.5-fold after increasing the daily dose from 150 mg every eight hours to 300 mg every eight hours. There was a trend towards a decrease in the volume of distribution (Vd) of digoxin and a decrease in non-renal clearance during combined therapy, with decreases being more significant with the higher dose of propafenone. It was suggested that the mechanism of the interaction is related to decreases in the Vd and non-renal elimination of digoxin. This trial suggests that monitoring of digoxin serum levels are indicated during concomitant propafenone therapy, especially with higher doses of propafenone. In addition, as the interaction is dose-related, digoxin serum levels should be monitored closely when doses of propafenone are increased 5.
Common questions
Can I take Digoxin and Propafenone together?
Increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Propafenone 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 "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 Propafenone 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: 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
- Product Information: DIGOXIN intravenous injection, digoxin intravenous injection. Hikma Pharmaceuticals USA Inc. (per Dailymed), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: LANOXIN® intravenous, intramuscular injection, digoxin intravenous, intramuscular injection. Covis Pharma (per FDA), King of Prussia, PA, 2025. DailyMed
- Nolan PE, Marcus FI, Erstad BL, et al: Effects of coadministration of propafenone on the pharmacokinetics of digoxin in healthy volunteer subjects. J Clin Pharmacol 1989; 29:46-52. DOI
Keep reading about Digoxin
Keep reading about Propafenone
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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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