Digoxin and Trimethoprim: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Digoxin
Trimethoprim
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
An increased digoxin exposure
Interaction Deep Dive
Coadministration of digoxin and trimethoprim resulted in a 22% to 28% increase in digoxin serum concentrations12; increases of 30% to 50% have been reported in elderly patients 3. Measure digoxin concentrations prior to initiation of concurrent use. Reduce the digoxin dose (by approximately 15% to 30% for oral) or modify the dosing frequency. Continue monitoring digoxin plasma concentration levels. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing trimethoprim 12.
Why it happens (mechanism)
Reduced renal tubular secretion of digoxin
Literature reports
3 reports — tap to read
a) In pharmacokinetic studies, coadministration of digoxin and trimethoprim resulted in a 22% to 28% increase in digoxin serum concentrations 12.
b) A study of 9 elderly patients stabilized on digoxin therapy showed that the addition of trimethoprim 200 mg twice daily for 2 weeks significantly altered the serum concentrations of digoxin. All patients had normal serum creatinine values and no signs of hepatic or cardiac disease. Immediately prior to the addition of trimethoprim, digoxin serum concentrations averaged 1.0 nmol/L. Serum digoxin concentrations increased to 1.3 nmol/L after 7 days of trimethoprim administration and 1.5 nmol/L after 14 days. Seven days after the discontinuation of trimethoprim, digoxin levels had decreased to 0.9 nmol/L 3.
c) Six healthy young male subjects received a single IV infusion of digoxin 1 mg over 15 minutes, followed by 4 days of intermittent venous blood samples. On the fifth day, participants were started on oral trimethoprim 200 mg twice daily. Another IV dose of digoxin was given on day 10. Digoxin renal clearance was reduced by 17%, from an average of 1.93 mL/min/kg to 1.61 mL/min/kg. Digoxin total body clearance, extra renal clearance, and glomerular filtration rate were not significantly affected by the administration of trimethoprim 3.
Common questions
Can I take Digoxin and Trimethoprim together?
An increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Trimethoprim 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 Trimethoprim 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
- Petersen P, Kastrup J, Bartram R, et al: Digoxin-trimethoprim interaction. Acta Med Scand 1985; 217:423-427. PubMed
Keep reading about Digoxin
Keep reading about Trimethoprim
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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