Digoxin and Itraconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Itraconazole
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 and an increased risk of digoxin toxicity (nausea, vomiting, arrhythmias)
Interaction Deep Dive
Several reports demonstrate that concurrent use of itraconazole and digoxin can lead to elevation of digoxin serum levels resulting in toxicity876. During pharmacokinetic studies, coadministration of digoxin and itraconazole resulted in an 80% increase in digoxin serum concentrations. Measure digoxin concentrations prior to initiation of concurrent use. Reduce digoxin concentrations by reducing the digoxin dose by approximately 30% to 50% or by modifying the dosing frequency. Continue monitoring digoxin exposure124. Also, monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing itraconazole 3.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of digoxin
Literature reports
6 reports — tap to read
a) During pharmacokinetic studies, coadministration of digoxin and itraconazole resulted in an 80% increase in digoxin serum concentrations 12.
b) A study reported the case of a 78-year-old man who had been stabilized on digoxin 0.25 mg daily for two years (serum digoxin level was 1.4 mcg/L or 1.79 nanomol/L); other medications included furosemide and warfarin. Thirteen days after oral itraconazole 400 mg daily was added to his regimen, he experienced blurred vision, nausea, and vomiting. Five days later the itraconazole was discontinued, but the symptoms continued and worsened. Eight days later the patient was admitted with sinus bradycardia and a temporary pacemaker was inserted. His serum digoxin level was 5.6 mcg/L (7.17 nanomol/L); digoxin was discontinued and the serum level decreased over the next several days 5.
c) A 67-year-old COPD patient was treated with itraconazole 200 mg daily for an Aspergillus fumigatus respiratory infection. His drug regimen included inhaled bronchodilators and steroids, verapamil 240 mg, and digoxin 250 mcg daily (serum level, 2.1 nanomol/L (nmol/L)). Nine days after initiation of itraconazole, the patient complained of lethargy and nausea; his digoxin serum concentration was measured at 5.4 nmol/L. Digoxin was discontinued and the serum concentration dropped to 2.7 nmol/L after four days; after another four days, the serum level was 1.2 nmol/L. Digoxin was restarted at 62.5 mcg daily with regular monitoring scheduled 6.
d) The effect of itraconazole on the pharmacokinetics of digoxin was studied in ten healthy volunteers. Subjects were randomized to receive itraconazole 200 mg once daily for five days or placebo. On day 3 each subject received a single oral dose of digoxin 0.5 mg. The average area under the plasma concentration curve was significantly increased by approximately 50% and the renal excretion of digoxin was significantly decreased by 20% during administration of itraconazole. Although the peak plasma concentration and half-life of digoxin were increased the change was not statistically significant. It was proposed that itraconazole inhibited the P-gp mediated renal excretion of digoxin 7.
e) A 60 year-old renal transplant patient on tacrolimus experienced digoxin toxicity after receiving itraconazole and digoxin concomitantly. The patient had symptoms of shortness of breath, edema, decreased urine output, and nephrotoxicity. Electrocardiography showed atrial fibrillation with a ventricular rate of 90 to 105 beats per minute (BPM). Serum creatinine (SCr) was 4.7 mg/dL (415 mcmol/L) and hemodialysis was initiated. Tacrolimus trough level was 8 nanogram/mL (ng/mL); 9.9 nanomol/L (nmol/L) on 2 mg twice daily. Seven days after discharge the patient was readmitted in atrial fibrillation with a ventricular rate of 30 BPM. Serum digoxin levels were 3.9 ng/mL (4.99 nmol/L), tacrolimus blood level was 16.7 ng/mL (20.77 nmol/L), SCr was 7.9 mg/dL (698.4 mcmol/L). Ventricular rate increased to 61 BPM 7 hours after digoxin, atenolol, and dilTIAZem were discontinued. Serum digoxin levels decreased from 3.9 ng/mL (4.99 nmol/L) to 2 ng/mL (2.6 nmol/L) over the next 5 days 8.
f) A 49 year-old Asian male with end-stage renal disease developed digoxin toxicity after receiving itraconazole therapy. The patient presented with fever, cough with hemoptysis, shortness of breath, and malaise for 4 days. Bronchoscopy cultures revealed Aspergillus niger and the patient was treated with amphotericin B lipid complex (ABLC) for 1.5 months. Itraconazole was initiated after the course of ABLC was completed. The patient developed headache, chills, fever, and chest pain several days after itraconazole was initiated. One week later he developed vomiting and blurred vision and presented to the emergency room with sinus bradycardia, SCr 2.7 ng/mL (23.9 nmol/L), and serum digoxin level 3.9 ng/mL (4.99 nmol/L). Digoxin was discontinued and symptoms subsequently resolved. The author suggests appropriate monitoring with concomitant use of itraconazole and digoxin 8.
Common questions
Can I take Digoxin and Itraconazole together?
Increased digoxin exposure and an increased risk of digoxin toxicity (nausea, vomiting, arrhythmias) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Itraconazole 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 Itraconazole 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 (8)
- 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: SPORANOX(R) oral solution, itraconazole oral solution. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2024. DailyMed
- McClean KL & Sheehan GJ: Interaction between intraconazole and digoxin (letter). Clin Infect Dis 1994; 18:259-260.
- Alderman CP & Jersmann HPA: Digoxin-itraconazole interaction. Med J Aust 1993; 159:838-839. PubMed
- Jalava KM, Partanen J, & Neuvonen PJ: Itraconazole decreases renal clearance of digoxin. Ther Drug Monit 1997; 19:609-613. DOI
- Mathis S & Friedman G: Coadministration of digoxin with itraconazole in renal transplant recipients. Am J Kidney Dis 2001; 37(2):1-8. PubMed
Keep reading about Itraconazole
Keep reading about Digoxin
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