Spironolactone with Digitoxin Interaction Details
Brand Names Associated with Spironolactone
- Aldactone®
- Carospir®
- Spironolactone
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 13, 2023
Interaction Effect
Increased or decreased digitoxin elimination
Interaction Summary
Studies have demonstrated spironolactone induction of digitoxin hepatic metabolism resulting in a shorter digitoxin half-life. However, in one crossover study performed in three subjects, spironolactone administration increased the digitoxin half-life . Further studies in humans are needed to confirm the effects of spironolactone administration on digitoxin pharmacokinetics and to determine clinical significance.
Severity
Moderate
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Monitor digitoxin patients more closely when adding spironolactone to therapy or changing spironolactone dosage.
Mechanism Of Interaction
Induction of hepatic enzymes by spironolactone
Literature Reports
A) The effect of spironolactone on the metabolism of intravenously administered tritium-labelled digitoxin was studied in eight patients who had been receiving oral digitoxin 0.1 mg daily for at least eight weeks . The study was done in three patients taking digitoxin but not spironolactone, three patients before and during spironolactone administration, and two patients on digitoxin plus spironolactone. For the five patients receiving both drugs, oral spironolactone 400 mg daily was administered for at least 10 days prior to injection of tritium-labelled digitoxin. Spironolactone affected digitoxin metabolism significantly; fraction of unchanged digitoxin excreted in urine decreased from 79% to 66%, and fraction of water soluble compounds excreted in urine increased from 12% to 26% (p less than 0.05). Spironolactone also caused a 20% (p less than 0.01) decrease in the half-life of serum radioactivity and a 16% (p less than 0.05) decrease in volume of distribution. The changes in the composition of urinary metabolites was due to spironolactone induction of digitoxin hepatic metabolism. The authors concluded that this interaction was of minor clinical importance because the observed changes fell within the range of inter-individual variability for digitoxin pharmacokinetics.
B) The effects of oral cholestyramine and oral spironolactone 300 mg daily on the elimination rate of digitoxin was studied in six healthy subjects in order to evaluate the benefit of cholestyramine and spironolactone in the treatment of digitoxin toxicity . A crossover study was performed on three of the subjects who received digitoxin plus spironolactone and digitoxin plus placebo. Digitoxin 0.1 to 0.15 mg daily was administered for 30 days followed by spironolactone or placebo daily for eight days. Subjects then recommenced daily digitoxin to perform crossover study. The administration of spironolactone increased digitoxin half-life from 141.6 to 192.2 hours (p less than 0.01). The reason for this increase was unknown, and the authors concluded that spironolactone administration may be contraindicated in digitoxin toxicity.
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.