Digoxin with Itraconazole Interaction Details
Brand Names Associated with Digoxin
- Cardoxin®
- Digitek®
- Digoxin
- Lanoxicaps®
- Lanoxin®
Brand Names Associated with Itraconazole
- Itraconazole
- Onmel®
- Sporanox®
- Tolsura®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 08, 2024
Interaction Effect
An increased risk of digoxin toxicity (nausea, vomiting, arrhythmias)
Interaction Summary
Several reports demonstrate that concurrent use of itraconazole and digoxin can lead to elevation of digoxin serum levels resulting in toxicity. Proposed mechanisms for these changes include inhibition of metabolism of digoxin and inhibition of renal elimination of digoxin . 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 plasma concentration levels .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Coadministration of digoxin and itraconazole may increase digoxin plasma 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 plasma concentration levels.
Mechanism Of Interaction
Inhibition of digoxin metabolism and clearance
Literature Reports
A) During pharmacokinetic studies, coadministration of digoxin and itraconazole resulted in an 80% increase in digoxin serum concentrations .
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 .
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 .
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-glycopeptide mediated renal excretion of digoxin .
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 .
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 .
Digoxin Overview
-
Digoxin is used to treat heart failure and abnormal heart rhythms (arrhythmias). It helps the heart work better and it helps control your heart rate.
Itraconazole Overview
-
Itraconazole capsules (Sporanox, Tolsura) are used to treat fungal infections in the lungs that can spread throughout the body. Itraconazole capsules (Sporanox) are also used to treat fungal infections of the fingernails and toenails. Itraconazole oral solution (liquid) is used to treat yeast infections of the mouth and throat or of the esophagus (tube that connects the throat to the stomach). Itraconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.