Indomethacin and Digoxin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Indomethacin
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
Interaction Deep Dive
Coadministration of digoxin and indomethacin may increase digoxin exposure. Drugs that affect renal function, like indomethacin (NSAID) may impair the excretion of digoxin. Measure digoxin concentrations prior to initiation of concurrent use. Reduce digoxin concentrations by reducing the digoxin dose by approximately 15% to 30% or by modifying 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 indomethacin12.
Why it happens (mechanism)
Reduced GFR or tubular secretion; impaired secretion of digoxin
Literature reports
5 reports — tap to read
a) During pharmacokinetic studies, coadministration of digoxin and indomethacin resulted in a 40% increase in digoxin serum concentrations 12.
b) The renal depressant effects of indomethacin contributed to increased digoxin serum levels in an 1800 gram male infant being treated for congestive heart failure caused by persistent patent ductus arteriosus 3.
c) A case study reported toxic levels of digoxin when indomethacin was added in a full-term neonate. In this case, serum digoxin rose to 8.2 nanogram/mL (ng/mL; 10.5 nanomol/L) with a pronounced reduction in urine output. Clinical signs of toxicity were not apparent 4.
d) Concomitant therapy with oral indomethacin and digoxin was reported to result in significant elevations in serum digoxin concentrations, to potentially toxic levels, in preterm infants (from 2.2 to 3.2 nanogram/mL or 2.82 to 4.1 nanomol/L). This effect was correlated with a decrease in urine output. The half-life of digoxin increased significantly (to 97 hours) following indomethacin as compared with age-matched controls (half-life 43 hours). The authors suggest that digoxin dosages be reduced by 50% when indomethacin is added to digoxin therapy in preterm infants 5.
e) A study reported an increase in serum digoxin (from 0.73 +/- 0.34 to 1.02 +/- 0.43 nanomol/L) in 10 patients who were receiving chronic digoxin therapy when indomethacin 50 mg three times daily was added to their regimen. Eight patients who received concomitant ibuprofen 600 mg three times daily did not experience an alteration in steady-state serum digoxin concentration 6.
Common questions
Can I take Indomethacin and Digoxin together?
Increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Indomethacin and Digoxin 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.
Questions for your pharmacist
- Does my dose of Indomethacin or Digoxin 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 (6)
- 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
- Schimmel MS, Inwood RJ, Eidelman AI, et al: Toxic digitalis levels associated with indomethacin therapy in a neonate. Clin Pediatr 1980; 19:768-769. PubMed
- Haig GM & Brookfield EG: Increase in serum digoxin concentrations after indomethacin therapy in a full-term neonate. Pharmacotherapy 1992; 12:334-336. DOI
- Koren G, Zarfin Y, Perlman M, et al: Effects of indomethacin on digoxin pharmacokinetics in preterm infants. Pediatr Pharmacol 1984; 4:25-30.
- Jorgensen HS, Christensen HR, & Kampmann JP: Interaction between digoxin and indomethacin or ibuprofen. Br J Clin Pharmacol 1991; 31:108-110. PubMed
Keep reading about Indomethacin
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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