Verapamil with Digoxin Interaction Details

Brand Names Associated with Verapamil

Brand Names Associated with Digoxin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 08, 2024

Interaction Effect

Increased serum digoxin concentrations and risk of digitalis toxicity; increased risk of complete heart block

Interaction Summary

Coadministration of digoxin and verapamil may have additive effects on AV node conduction and increase the risk of bradycardia and advanced or complete heart block. Coadministration of verapamil with oral digoxin increased digoxin serum concentration by 50% to 75%; coadministration with IV digoxin increased digoxin AUC by 24%. Measure digoxin concentrations prior to initiation of concurrent use. Reduce the oral digoxin dose by approximately 30% to 50% or the IV or IM digoxin dose by approximately 15% to 30%, or modify the dosing frequency. Continue monitoring digoxin plasma concentration levels. Increases in serum digoxin levels may result in digitalis toxicity, and the effect may be magnified in patients with hepatic cirrhosis. In patients with mild ventricular dysfunction, optimum doses of digitalis and/or diuretics should be established prior to initiating verapamil. If verapamil is stopped after concurrent therapy, digoxin levels should be monitored and doses adjusted accordingly, to avoid under-digitalization .

Severity

Major

Onset

Rapid

Evidence

Established

How To Manage Interaction

Coadministration of digoxin and verapamil may have additive effects on AV node conduction and increase the risk of bradycardia and advanced or complete heart block. Measure digoxin concentrations prior to initiation of concurrent use. Reduce the oral digoxin dose by approximately 30% to 50% or the IV or IM digoxin dose by approximately 15% to 30%, or modify the dosing frequency. Continue monitoring digoxin plasma concentration levels. Increases in serum digoxin levels may results in digitalis toxicity, and the effect may be magnified in patients with hepatic cirrhosis. In patients with mild ventricular dysfunction, optimum doses of digitalis and/or diuretics should be established prior to initiating verapamil. If verapamil is stopped after concurrent therapy, digoxin levels should be monitored and doses adjusted accordingly, to avoid under-digitalization .

Mechanism Of Interaction

Inhibition of renal and/or extrarenal digoxin clearance; additive effects on AV node conduction

Literature Reports

A) During pharmacokinetic studies, coadministration of oral digoxin and verapamil resulted in a 50% to 75% increase in digoxin serum concentrations . Coadministration of IV digoxin and verapamil resulted in a 24% increase in digoxin AUC .

B) In clinical trials in patients receiving verapamil for ventricular control and digoxin for atrial fibrillation or flutter, 15% of patients had ventricular rates below 50 beats/minute at rest and 5% of patients experienced asymptomatic hypotension .

C) Serum digoxin concentrations increased gradually and linearly during the first few days of verapamil therapy, reached 90% of the peak value by 7 days, and peak values by 14 days. The interaction is dose-dependent and occurs at all levels of digitalization . After 5 to 6 weeks of verapamil therapy, plasma digoxin concentrations declined from about 60% to 30% above pre-verapamil levels and renal clearance normalized. Extrarenal clearance of digoxin remains affected and patients with renal failure may be more likely to experience persistent elevations in digoxin levels .

D) Concomitant verapamil and digoxin therapy was reported to increase serum digoxin levels from 0.96 to 1.63 nanogram/mL (1.229 to 2.087 nanomol/L) in 41 patients treated with verapamil 240 mg daily for chronic atrial fibrillation .

E) A study evaluated the pharmacokinetics of digoxin during concomitant verapamil therapy in patients with chronic atrial fibrillation. Verapamil in doses of 240 mg daily was administered to patients receiving maintenance digoxin doses, resulting in significant increases in digoxin serum concentrations (from 0.76 to 1.31 nanogram/mL or 0.973 to 1.677 nanomol/L). These effects were reported to be dose-dependent. In 7 of 49 patients evaluated, signs and symptoms of digitalis toxicity were observed. Steady state serum digoxin concentrations were achieved approximately 1 week after administration of verapamil. Following discontinuation of the drug, elevated serum digoxin levels persisted for at least 10 hours, but when patients were retested 2 weeks later the digoxin serum concentrations had returned to baseline levels. The effect of verapamil on digoxin distribution is explained partially by reduced renal excretion of digoxin, without a reduction in glomerular filtration .

F) A study reported a more pronounced interaction of verapamil and digoxin in patients with cirrhosis. Concurrent therapy with a single low dose of oral verapamil 80 mg and oral digoxin 0.5 mg in cirrhotic patients was reported to result in a significant 32% increase in the AUC and peak serum levels of digoxin, with an associated 23% decrease in renal digoxin clearance. In normal subjects, much smaller alterations in digoxin kinetics were observed during concurrent verapamil administration .

G) One report found the addition of oral verapamil 320 mg daily (range, 160 mg to 480 mg daily) provided increased control of ventricular response rates in digitalized patients with chronic atrial fibrillation. Heart rates at rest and during exercise were significantly reduced following the addition of verapamil. Although mean serum digoxin levels increased from 1.6 to 2.7 nanogram/mL (2.05 to 3.46 nanomol/L), clinical signs of digitalis toxicity were not present .

H) The inotropic activity of digoxin appears to be enhanced during concomitant verapamil therapy. Evidence suggests that this effect is due to the elevated plasma digoxin concentration induced by verapamil, rather than verapamil itself . Ventricular fibrillation and death occurred in a 73-year-old patient following the addition of oral verapamil 80 mg twice daily to digoxin therapy (0.25 mg daily). In a 77-year-old patient receiving digoxin 0.25 mg daily, asystole occurred following intravenous verapamil in aliquots of 5 mg for a total of 35 mg over a period of 130 minutes. In both patients, addition of verapamil was of no benefit in controlling rapid heart rate. In both patients, death occurred when digoxin levels reached 4 nanogram/mL (5.1 nanomol/L) .

Verapamil Overview

• Verapamil is used to treat high blood pressure and to control angina (chest pain). The immediate-release tablets are also used alone or with other medications to prevent and treat irregular heartbeats. Verapamil is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart and slows electrical activity in the heart to control the heart rate.

• 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.

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.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.