Spironolactone and Digoxin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Spironolactone
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 spironolactone (P-gp inhibitor) may increase digoxin exposure. Measure digoxin exposure before initiating concomitant drugs. Reduce digoxin concentrations by decreasing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing spironolactone2354.
Why it happens (mechanism)
Inhibition of P-gp mediated efflux transport of digoxin
Literature reports
7 reports — tap to read
a) During pharmacokinetic studies, coadministration of spironolactone and oral digoxin resulted in a 25% increase in digoxin serum concentrations 23. Coadministration of spironolactone and IV digoxin resulted in a 17% increase in a 44% increase in digoxin AUC 54.
b) The mechanism of renal handling of digoxin and spironolactone were evaluated 6. Simultaneous measurements of inulin and digoxin clearances were performed in 13 digitalized patients with chronic congestive heart disease. Nine of the patients were subsequently treated with spironolactone 100 mg daily for 10 days, and the measurements of inulin and digoxin clearances were repeated. The mean concentration of plasma digoxin increased from 0.8 nanogram/mL (ng/mL; 1.02 nanomol/L) to 1 ng/mL (1.3 nanomol/L; p less than 0.01). The data suggests that spironolactone decreases tubular secretion of digoxin in the distal segment of the renal tubulus. Digoxin radioimmunoassays free of cross-reactivity with spironolactone and its metabolites were utilized in this study 7.
c) A study was performed on four patients with arteriosclerotic heart disease and four healthy volunteers 8. The subjects were administered 0.75 mg digoxin intravenously, producing serum levels of 0.93 to 2.4 nanogram/mL (ng/mL; 1.191 to 3.07 nanomol/L). The subjects then received spironolactone 100 mg twice daily for 5 days followed by another IV digoxin 0.75 mg dose. Digoxin serum levels were 1.1 to 3.55 ng/mL (1.41 to 4.545 nanomol/L). During spironolactone administration plasma and renal clearance of digoxin and digoxin volume of distribution decreased significantly. The authors concluded that both the loading dose and maintenance dosage for digoxin may need to be reduced when taking spironolactone concurrently; also, further studies are needed to evaluate whether spironolactone displaces digoxin from receptor sites where digoxin exerts its therapeutic effect. Digoxin radioimmunoassays free of cross-reactivity with spironolactone and its metabolites were utilized in this study 7.
d) The effect of quiNIDine and spironolactone on the pharmacokinetics of digoxin were studied in 6 normal subjects who each received digoxin alone, digoxin with quiNIDine, digoxin with spironolactone, and digoxin with both quiNIDine and spironolactone 9. Spironolactone and quinidine, alone and in combination, reduced digoxin systemic, renal, and nonrenal clearance and prolonged the elimination half-life of digoxin. However, this study may not be valid due to the possible inclusion of spironolactone metabolites by the digoxin radioimmunoassay utilized 10.
e) Digoxin kinetic and hemodynamic studies were evaluated in 6 healthy volunteers during digoxin administration alone and digoxin plus spironolactone or triamterene. Spironolactone reduced renal tubular secretion of digoxin and attenuated digoxin's positive inotropic effect. Results also indicated a drug-receptor interaction between spironolactone metabolites and digoxin at the hypothesized inotropic digitalis receptor. However, this study may not be valid due to the possible inclusion of spironolactone metabolites by the digoxin radioimmunoassay utilized 11.
f) The effect of spironolactone on digoxin pharmacokinetics in pediatric patients with ventricular septal defects were studied. Twenty-three children (2 weeks to 3 1/2 years in age; 1.5 to 15 kg in weight) were concurrently administered digoxin 9.3 +/- 4.7 mcg/kg/day and spironolactone 2.4 +/- 0.9 mg/kg/day. None of the 23 children exhibited digoxin serum concentrations greater than 2.2 nanogram/mL (2.82 nanomol/L) or signs of toxicity. A second group of eight children (2 weeks to 3 1/2 years in age) received digoxin 7.5 mcg/kg/day as a single agent for at least 14 days; spironolactone 2.96 +/- 0.65 mg/kg/day was then added to the regimen. None of the eight children had elevated serum digoxin levels following administration of spironolactone 12.
g) Spironolactone used concurrently with digoxin can interfere with the radioimmunoassay commonly used for monitoring digoxin serum levels. This occurs due to the structural similarity of spironolactone and its metabolites to digoxin 1. However, many clinicians have reported negligible interference with digoxin radioimmunoassay if therapeutic doses of spironolactone are administered 131415.
Common questions
Can I take Spironolactone and Digoxin together?
Increased digoxin exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Spironolactone 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Spironolactone 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 (15)
- Product Information: LANOXIN(R) intravenous injection, intramuscular injection, digoxin intravenous injection, intramuscular injection. Covis Pharmaceuticals, Inc. (per FDA), Cary, NC, 2013. DailyMed
- 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
- Steiness E: Renal tubular secretion of digoxin. Circulation 1974; 50:103-107. PubMed
- Thomas RW & Maddox RR: The interaction of spironolactone and digoxin: a review and evaluation. Ther Drug Monit 1981; 3:117-120. DOI
- Waldorff S, Andersen JD, Heeboll-Nielsen N, et al: Spironolactone-induced changes in digoxin kinetics. Clin Pharmacol Ther 1978; 24:162-167. PubMed
- Fenster PE, Hager WD, & Goodman MM: Digoxin-quinidine-spironolactone interaction. Clin Pharmacol Ther 1984; 36:70-73. DOI
- Hedman A, Angelin B, Arvidsson A, et al: Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance. Eur J Clin Pharmacol 1992; 42:481-485. PubMed
- Waldorff S, Hansen PB, Egeblad H, et al: Interactions between digoxin and potassium sparing diuretics. Clin Pharmacol Ther 1983; 33:418-423. PubMed
- Koren G: Interaction between digoxin and commonly coadministered drugs in children. Pediatrics 1985; 75:1032-1037. DOI
- Ravel R: Negligible interference by spironolactone and prednisone in digoxin radioimmunoassay. Clin Chem 1975; 21:1801. DOI
- Personal Communication: Adam Myers, MD. Denver General Hospital, Denver, CO, Aug, 1982a.
- Personal Communication: Earl W Sutherland, MD, PhD, Assistant Professor of Medicine. University of Colorado School of Medicine, Denver, CO, Aug, 1982b.
Keep reading about Spironolactone
Keep reading about Digoxin
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