Prescription ·Moderate evidence ·Reviewed May 2026
Digoxin is a cardiac glycoside used for rate control in atrial fibrillation and symptomatic improvement in heart failure with reduced ejection fraction. The DIG trial showed it reduces hospitalizations but not mortality in heart failure. It has a narrow therapeutic index, requiring careful dosing and monitoring.
The bottom line
Evidence rating moderate. Most-documented uses: rate control in atrial fibrillation (especially at rest), reduces heart failure hospitalizations (dig trial), positive inotropic effect. 10 sources indexed (2015–2022), with 11 interaction records on file.
Core mechanism
Inhibits the sodium-potassium ATPase (Na+/K+ pump) in cardiomyocytes, leading to increased intracellular sodium, which reduces calcium extrusion via the Na+/Ca2+ exchanger. The resulting increased intracellular calcium enhances contractility (positive inotrope). Also increases vagal tone and decreases sympathetic activity, slowing AV nodal conduction and heart rate. Centrally sensitizes baroreceptors, reducing neurohormonal activation in HF.
Can be taken with or without food; high-fiber meals and kaolin-pectin antacids can reduce absorption; primarily renally eliminated
Berberine inhibits P-glycoprotein, increasing digoxin bioavailability. Digoxin has a narrow therapeutic index.
Recommendation: Avoid combining without medical supervision and digoxin level monitoring. Risk of digoxin toxicity.
Hypomagnesemia increases sensitivity to digoxin toxicity by altering the cardiac sodium-potassium ATPase that digoxin inhibits. Maintaining adequate magnesium levels is important for preventing digoxin-related cardiac arrhythmias. Many patients on digoxin also take diuretics that deplete magnesium.
Recommendation: Monitor magnesium levels regularly while on digoxin. Maintain adequate magnesium intake through supplementation if needed (200-400mg/day). Be especially vigilant if also taking diuretics that deplete magnesium.
Hypokalemia dramatically increases the risk of digoxin toxicity, including life-threatening cardiac arrhythmias. Conversely, hyperkalemia with digoxin can also be dangerous. Potassium levels must be kept within a very narrow range for safe digoxin therapy.
Recommendation: Monitor potassium levels closely while on digoxin. Target serum potassium of 4.0-5.0 mEq/L. Potassium supplementation may be needed, especially if also taking diuretics, but avoid oversupplementation. Discuss with your prescriber.
St. John's Wort significantly reduces digoxin levels through potent P-glycoprotein induction. A landmark study showed that St. John's Wort reduced digoxin AUC by 25%, which can lead to loss of therapeutic effect and potential decompensation in heart failure patients.
Recommendation: Do not combine St. John's Wort with digoxin. The reduction in digoxin levels can lead to loss of rate control or worsening heart failure. If already taking both, consult your cardiologist before making changes.
Amiodarone increases digoxin levels by 70-100% through inhibition of P-glycoprotein and reduction of renal and non-renal clearance. This can cause potentially fatal digoxin toxicity with cardiac arrhythmias.
Recommendation: Reduce digoxin dose by 50% when starting amiodarone. Monitor digoxin levels closely. Watch for toxicity signs (nausea, visual changes, bradycardia, arrhythmias).
High-dose vitamin D3 can cause hypercalcemia, and hypercalcemia can make digoxin-related rhythm problems more likely. This is not a routine-dose vitamin D issue for most people, but it becomes clinically important with high-dose D3, accidental overuse, kidney disease, granulomatous disease, or concurrent calcium supplements. Symptoms can include nausea, confusion, weakness, visual changes, palpitations, or fainting.
Recommendation: Avoid high-dose vitamin D3 while taking digoxin unless your clinician is monitoring calcium and kidney function. If you need vitamin D repletion, use the prescribed dose and ask when calcium should be rechecked. Seek urgent care for fainting, new irregular heartbeat, severe weakness, confusion, or persistent vomiting.
Large or repeated calcium supplement doses can cause hypercalcemia in susceptible people, particularly with kidney disease, dehydration, thiazide use, or concurrent vitamin D. Hypercalcemia can increase the heart's sensitivity to digoxin and may contribute to conduction problems or arrhythmias. Routine dietary calcium is not the concern; high-dose supplementation and calcium-alkali syndrome are.
Recommendation: Do not take high-dose calcium supplements while on digoxin unless your clinician is monitoring calcium and kidney function. Stay within the prescribed daily elemental calcium target and avoid stacking multiple calcium-containing products. Seek urgent care for fainting, new irregular heartbeat, severe weakness, confusion, or persistent vomiting.
Activated charcoal binds digoxin in the gastrointestinal tract and can sharply reduce absorption when taken near a dose. Because digoxin has a narrow therapeutic window, reduced absorption can worsen atrial fibrillation rate control or heart failure symptoms. Charcoal is used medically for selected poisonings and is not a routine detox supplement for people taking digoxin.
Recommendation: Avoid activated charcoal supplements while taking digoxin unless a clinician specifically directs it. If a one-time charcoal dose is unavoidable outside an emergency setting, separate it from digoxin by at least 6 hours and tell your prescriber if palpitations, swelling, or shortness of breath worsen.
Psyllium husk is a bulk-forming fiber similar to ispaghula, which has reduced digoxin bioavailability in human studies. Taking psyllium close to digoxin can lower digoxin exposure and may reduce heart rate or heart failure control. The risk is highest when fiber timing changes suddenly in older adults or people maintained near the low end of the therapeutic range.
Recommendation: Take psyllium husk at least 4 hours away from digoxin and keep your fiber routine consistent from day to day. Tell your prescriber if you start or stop daily psyllium, because symptoms or digoxin levels may need monitoring.
Berberine may increase oral digoxin exposure by inhibiting intestinal P-glycoprotein. Digoxin has a narrow therapeutic index, so even moderate changes in exposure can increase the risk of nausea, visual changes, bradycardia, or arrhythmia.
Recommendation: Do not combine berberine with digoxin without prescriber approval. If both are used, monitor for digoxin toxicity and ask your clinician whether a digoxin level is needed after berberine is started or stopped.
Berberine HCl may increase oral digoxin exposure by inhibiting intestinal P-glycoprotein. Digoxin has a narrow therapeutic index, so even moderate changes in exposure can increase the risk of nausea, visual changes, bradycardia, or arrhythmia.
Recommendation: Do not combine berberine HCl with digoxin without prescriber approval. If both are used, monitor for digoxin toxicity and ask your clinician whether a digoxin level is needed after berberine HCl is started or stopped.
Numbered references. Citations throughout the page link here.
Salcedo-Mingoarranz ÁL, García-Díaz B, Barcia-Hernández E. Population pharmacokinetics of digoxin in elderly patients: A systematic review. Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria. 2022
Abdel Jalil M, Abdullah N, Alsous M et al.. Population Pharmacokinetic Studies of Digoxin in Adult Patients: A Systematic Review. European journal of drug metabolism and pharmacokinetics. 2021
Abdel Jalil MH, Abdullah N, Alsous MM et al.. A systematic review of population pharmacokinetic analyses of digoxin in the paediatric population. British journal of clinical pharmacology. 2020
Qureshi W, O'Neal WT, Soliman EZ et al.. Systematic review and meta-analysis of mortality and digoxin use in atrial fibrillation. Cardiology journal. 2016
Ziff OJ, Lane DA, Samra M et al.. Safety and efficacy of digoxin: systematic review and meta-analysis of observational and controlled trial data. BMJ (Clinical research ed.). 2015
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