Digoxin and Verapamil: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Verapamil
Digoxin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased digoxin exposure, increased risk of digitalis toxicity and an increased risk of complete heart block
Interaction Deep Dive
Coadministration of digoxin and verapamil (P-gp inhibitor and calcium channel blocker) may increase digoxin exposure, may also cause additive effects on AV node conduction which may result in bradycardia and advanced or complete heart block. Measure digoxin exposure before initiating concomitant drugs. Reduce digoxin concentrations by decreasing dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring2. Reduce digoxin exposure by reducing the dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing verapamil 43. 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, establish optimum doses of digitalis and/or diuretics prior to initiating verapamil. If verapamil is stopped after concurrent therapy, monitor digoxin levels and doses adjusted accordingly, to avoid under-digitalization 5.
Why it happens (mechanism)
Inhibition of P-gp mediated efflux transport of digoxin; additive effects on AV node conduction
Literature reports
8 reports — tap to read
a) During pharmacokinetic studies, coadministration of oral digoxin and verapamil resulted in a 50% to 75% increase in digoxin serum concentrations 12. Coadministration of IV digoxin and verapamil resulted in a 24% increase in digoxin AUC 43.
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 6.
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 7. 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 8.
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 9.
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 10.
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 11.
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 12.
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 13. 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) 14.
Common questions
Can I take Digoxin and Verapamil together?
Increased digoxin exposure, increased risk of digitalis toxicity and an increased risk of complete heart block Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin and Verapamil interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Digoxin or Verapamil need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (14)
- Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
- Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. DailyMed
- Product Information: DIGOXIN intravenous injection, digoxin intravenous injection. Hikma Pharmaceuticals USA Inc. (per Dailymed), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: LANOXIN® intravenous, intramuscular injection, digoxin intravenous, intramuscular injection. Covis Pharma (per FDA), King of Prussia, PA, 2025. DailyMed
- Product Information: Verelan(R) oral capsules, verapamil HCl oral capsules. Schwarz Pharma, LLC (per FDA), Smyrna, GA, 2011. DailyMed
- Product Information: Verelan(R) PM oral extended-release capsules, verapamil HCl oral extended-release capsules. Schwarz Pharma, LLC (per FDA), Smyrna, GA, 2011. DailyMed
- Klein HO & Kaplinsky E: Verapamil and digoxin. Their respective effects on atrial fibrillation and their interaction. Am J Cardiol 1982; 50:894-902. PubMed
- Pedersen KE, Dorph-Pedersen A, Hvidt S, et al: The long-term effect of verapamil on plasma digoxin concentration and renal digoxin clearance in healthy subjects. Eur J Clin Pharmacol 1982; 22:123-127. DOI
- Klein HO, Lang R, Di Segni E, et al: Verapamil-digoxin interaction. N Engl J Med 1980; 303:160. PubMed
- Klein HO, Lang R, Weiss E, et al: The influence of verapamil on serum digoxin concentration. Circulation 1982; 65:998-1003. DOI
- Maragno I, Gianotti C, Tropeano PF, et al: Verapamil-induced changes in digoxin kinetics in cirrhosis. Eur J Clin Pharmacol 1987; 32:309-311. PubMed
- Schwartz JB, Keefe D, Kates RE, et al: Acute and chronic pharmacodynamic interaction of verapamil and digoxin in atrial fibrillation. Circulation 1982a; 65:1163-1170. PubMed
- Pedersen KE, Thayssen P, Klitgaard NA, et al: Influence of verapamil on the inotropism and pharmacokinetics of digoxin. Eur J Clin Pharmacol 1983; 25:199-206. DOI
- Zatuchni J: Verapamil-digoxin interaction. Am Heart J 1984; 108:412-413. PubMed
Keep reading about Verapamil
Keep reading about Digoxin
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