Digoxin with Spironolactone Interaction Details
Brand Names Associated with Digoxin
- Cardoxin®
- Digitek®
- Digoxin
- Lanoxicaps®
- Lanoxin®
Brand Names Associated with Spironolactone
- Aldactone®
- Carospir®
- Spironolactone
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 08, 2024
Interaction Effect
Increased digoxin exposure
Interaction Summary
. Coadministration of spironolactone and oral digoxin resulted in a 25% increase in digoxin serum concentrations, and with IV digoxin resulted in a 44% increase in digoxin AUC . Measure digoxin concentrations prior to initiation of concurrent use. Reduce the digoxin dose by approximately 15% to 30%, or modify the dosing frequency and continue monitoring . Additionally, spironolactone may be incorrectly detected as digoxin at levels up to 0.5 nanogram/mL in some assays, resulting in falsely elevated digoxin levels. Consider using testing methods less susceptible to interference, such as LC/MS/MS, and monitor patients for signs of toxicity .
Severity
Major
Onset
Unspecified
Evidence
Probable
How To Manage Interaction
Coadministration of spironolactone and oral digoxin resulted in a 25% increase in digoxin serum concentrations, and with IV digoxin resulted in a 44% increase in digoxin AUC . Measure digoxin concentrations prior to initiation of concurrent use. Reduce the digoxin dose by approximately 15% to 30%, or modify the dosing frequency and continue monitoring .
Mechanism Of Interaction
Inhibition of active tubular secretion of digoxin
Literature Reports
A) During pharmacokinetic studies, coadministration of digoxin and spironolactone resulted in a 44% increase in digoxin AUC. Values regarding an increase in digoxin serum concentration were not available .
B) The mechanism of renal handling of digoxin and spironolactone were evaluated . 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 .
C) A study was performed on four patients with arteriosclerotic heart disease and four healthy volunteers . 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.
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 . 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 .
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 .
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 .
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 . However, many clinicians have reported negligible interference with digoxin radioimmunoassay if therapeutic doses of spironolactone are administered .
Digoxin Overview
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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.
Spironolactone Overview
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Spironolactone is used to treat certain patients with hyperaldosteronism (the body produces too much aldosterone, a naturally occurring hormone); low potassium levels; heart failure; and in patients with edema (fluid retention) caused by various conditions, including liver, or kidney disease. It is also used alone or with other medications to treat high blood pressure. Spironolactone is in a class of medications called aldosterone receptor antagonists. It causes the kidneys to eliminate unneeded water and sodium from the body into the urine but reduces the loss of potassium from the body.
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High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
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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.