Digoxin with Diltiazem Interaction Details

Brand Names Associated with Digoxin

Brand Names Associated with Diltiazem

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

Interaction Effect

Increased digoxin exposure; increased risk of complete heart block

Interaction Summary

Coadministration of digoxin and diltiazem 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 15% to 30% or modify the dosing frequency. Continue monitoring digoxin plasma concentration levels .

Severity

Major

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Coadministration of digoxin and diltiazem 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 15% to 30% or modify the dosing frequency. Continue monitoring digoxin plasma concentration levels .

Mechanism Of Interaction

Inhibition of digoxin clearance; additive effects on AV node conduction

Literature Reports

A) During pharmacokinetic studies, coadministration of oral digoxin and diltiazem resulted in a 20% increase in digoxin plasma concentrations .

B) A reduction in digoxin renal clearance was observed with the concurrent use of diltiazem. Eight volunteers received oral digoxin 0.25 mg/day alone for 13 days; and then, on day 14, diltiazem 30 mg four times daily was added and therapy continued for 15 more days. Trough blood samples were obtained throughout the study for digoxin concentration determination. Following the digoxin dose on days 13 and 28, urine was collected for 24 hours. The coadministration of diltiazem resulted in a significant elevation of the mean steady-state digoxin trough concentration from 0.32 to 0.48 nanogram (ng/mL; 0.41 to 0.615 nanomol/L). Seven subjects displayed elevated digoxin concentrations, one demonstrating a 0.3 mg/mL (0.38 mmol/L) increase. Elevations became evident within one week of concurrent therapy. Mean renal clearances significantly decreased from 223 to 153 mL/min. No change in CrCl was observed among the subjects between the two phases. The authors attributed the interaction to decreased tubular secretion since digoxin renal clearance decreased but creatinine clearance remained constant. However, the determination of only trough concentrations does not allow for full determination of total body clearance and Vd, which would permit a better analysis .

C) The effect of diltiazem on digoxin steady-state concentrations was studied in 11 patients with congestive heart failure. All patients were receiving a chronic stable oral dose of digoxin (nine were receiving 0.25 mg and two were receiving 0.125 mg) for at least 14 days. Prior to initiating diltiazem therapy (60 mg three times daily), blood samples were obtained immediately prior to and 3, 6, and 24 hours after a dose of digoxin. Similar blood levels were drawn after 3 days of concurrent diltiazem therapy. Additionally, digoxin trough samples were obtained following the first and seventh doses of digoxin during combined therapy. A significant increase (36%) in digoxin concentration was observed during the third day of concurrent therapy. Trough concentrations increased significantly from 1.1 nanogram/mL (ng/mL; 1.41 nanomol/L) with digoxin alone to 1.5 ng/mL (1.92 nanomol/L) on the seventh day of combined therapy. None of the patients demonstrated digoxin toxicity. The authors concluded that an interaction exists between diltiazem and digoxin, but is of minor clinical importance unless digoxin concentrations are initially at the upper limit of normal .

D) Not all investigators have observed an elevation in digoxin concentrations with the addition of diltiazem. Nine patients with organic heart disease (five with congestive heart failure (CHF); four with atrial fibrillation) who were receiving chronic oral digoxin 0.25 mg daily were studied. Prior to diltiazem therapy, a 24-hour urine collection and a mid-interval blood sample were obtained. Patients then received diltiazem 30 mg four times daily for 4 to 11 days (mean 7 days), which was eventually increased to 60 mg four times daily for an additional 5 to 20 days (mean 11 days). Blood and urine were collected for digoxin analysis at each diltiazem dose. No significant change in mean, midpoint digoxin concentrations or digoxin renal clearance were observed during either diltiazem phase. Only one patient demonstrated a clinically significant rise in digoxin concentration. The authors concluded that no interaction exists between digoxin and diltiazem .

E) A lack of change in digoxin trough concentrations following the concurrent administration of several different doses of diltiazem was reported. Eight subjects received digoxin 0.25 mg for one week at which time a trough blood sample was obtained. Diltiazem 30 mg four times daily was then coadministered for seven days before a second trough blood sample was obtained. This procedure was repeated for diltiazem 60 mg four times daily and 90 mg four times daily. No significant difference from baseline (0.85 nanogram/mL (ng/mL) or 1.088 nanomol/L) in any of the digoxin trough concentration with the addition of diltiazem was noted (0.86, 0.84, and 0.90 ng/mL or 1.101, 1.076, and 1.152 nanomol/L, respectively) .

F) It was of the opinion of the authors that diltiazem did not elevate digoxin concentrations. The results of another study might explain the conflicting results observed among the trials described above. Twelve patients with congestive heart failure who were receiving a stable oral dose of beta-acetyldigoxin (0.1 to 0.3 mg daily) for several weeks were entered into a trial. Trough blood samples for digoxin determination were obtained prior to the initiation of diltiazem (60 mg three times daily) and during diltiazem therapy. Urine was collected for a 24-hour period prior to and on several occasions during diltiazem therapy in nine patients. Mean digoxin concentrations did not increase with the coadministration of diltiazem overall. However, when looking at individual data, 8 of 12 patients displayed significant increases ranging from 24% to 70% (mean 46%) in digoxin plasma concentrations with the coadministration of diltiazem. In these individuals, total body clearance was reduced 28% (oral absorption was assumed to be 80%), but renal clearance remained unchanged, suggesting the interaction in these individuals occurred through nonrenal mechanisms. Mean total body clearance and renal clearance for the total study group was not reported. It should be noted that the calculation of total body clearance and renal clearance of digoxin was not optimal in this trial since only single trough samples were used .

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.

Diltiazem Overview

• Diltiazem is used to treat high blood pressure and to control angina (chest pain). Diltiazem 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.

• High blood pressure is a common condition, and when not treated it 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:

• 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.