Digoxin is a heart medicine used in heart failure and to control an irregular heart rhythm (atrial fibrillation). It strengthens the heartbeat and slows electrical conduction. It has a narrow margin between the effective and the toxic dose, so regular blood tests are required.
Furosemide-induced hypokalaemia increases Digoxin toxicity.
Furosemide is a loop diuretic that depletes potassium and magnesium, the electrolytes that most influence digitalis toxicity. Hypokalaemia increases digoxin binding to Na+/K+-ATPase and potentiates arrhythmias, even at therapeutic levels. This is a classic combination in heart failure patients, who use both drugs together. Monitor serum potassium (keep ≥ 4.0 mEq/L) and magnesium, correct deficits, monitor the ECG and consider digoxin level monitoring in unstable patients.
Loop diuretic + digoxin: diuretic-induced hypokalaemia and hypomagnesaemia increase digitalis toxicity. Monitor electrolytes and ECG.
Renal potassium loss sensitises the myocardium to Digoxin.
Electrolytes and digoxin levels; ECG if symptoms occur.
Nausea, anorexia, bradycardia, arrhythmias, confusion.
Monitor K+ and replace early; adjust the Digoxin dose if renal function changes.
DailyMed/FDA (NIH/NLM) — approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4 ; approved Furosemide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cdcd001-ab4b-4210-a455-2e17a7bc4972
Amiodarone raises plasma Digoxin levels, with risk of digitalis toxicity.
Amiodarone is a potent inhibitor of P-glycoprotein (P-gp), the transporter that eliminates digoxin at the intestinal, renal and biliary level. The inhibition reduces digoxin clearance and can raise its concentrations by 50–100%, with a risk of digitalis toxicity (nausea, arrhythmias, visual disturbances). The effect develops within days and persists for weeks after amiodarone is stopped (long half-life). The digoxin label recommends reducing the dose by about 30–50% when amiodarone is started and monitoring digoxin levels and the ECG. This combination is common in atrial fibrillation and requires tight control.
Amiodarone inhibits P-glycoprotein and can DOUBLE digoxin levels. Reduce the digoxin dose by 30–50% when starting and monitor digoxin levels.
Amiodarone inhibits P-glycoprotein and hepatic metabolism of Digoxin, potentially doubling its levels.
Digoxin levels from week 1 and symptom surveillance.
Nausea, yellow or blurred vision, bradycardia, arrhythmias.
Reduce the Digoxin dose (usually by half) and monitor serum levels.
DailyMed/FDA (NIH/NLM) — approved Amiodarone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51a88e8e-da02-4b97-9e7e-442fbffd908d ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Ketoconazole raises Digoxin concentrations, with a risk of digitalis toxicity.
Ketoconazole is a potent inhibitor of P-glycoprotein and CYP3A4, the two systems that eliminate digoxin. The inhibition increases oral bioavailability and reduces digoxin clearance, raising its concentrations and the risk of digitalis toxicity. Monitor digoxin levels when ketoconazole is started or adjusted, reduce the digoxin dose if needed and watch for toxicity symptoms (nausea, bradycardia, arrhythmias, visual disturbances), especially in prolonged treatment.
Ketoconazole inhibits P-glycoprotein and can raise digoxin levels. Monitor digoxin levels and toxicity signs.
P-glycoprotein inhibition by ketoconazole reduces digoxin elimination and increases its bioavailability.
Digoxin levels, ECG (bradycardia, arrhythmias), gastrointestinal and visual symptoms.
Nausea, vomiting, arrhythmias, yellow/green vision (xanthopsia).
Monitor digoxin levels and clinical signs; reduce the digoxin dose if needed. Watch closely in the elderly and in renal impairment.
DailyMed/FDA (NIH/NLM) — approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Azithromycin may raise plasma Digoxin levels by inhibiting P-glycoprotein, with a risk of digitalis toxicity.
Azithromycin, like other macrolides, can raise digoxin concentrations through two mechanisms: inhibition of P-glycoprotein (which eliminates digoxin) and reduction of the gut bacterial flora that inactivates digoxin (about 10% of patients have flora that metabolises the drug). The effect is variable, but reports of digitalis toxicity after macrolide courses exist. Monitor for toxicity symptoms (nausea, vomiting, bradycardia, arrhythmias, confusion, visual disturbances) and consider monitoring digoxin levels, especially in the elderly and in patients with reduced renal function.
Macrolides can raise digoxin levels (P-gp inhibition and reduction of the gut flora that metabolises digoxin). Monitor for signs of digitalis toxicity.
Azithromycin inhibits P-glycoprotein, the efflux transporter that clears Digoxin; inhibition raises serum digoxin and may trigger digitalis toxicity.
Monitor nausea, anorexia, visual disturbances, bradycardia/arrhythmias and digoxin and potassium levels.
Bradyarrhythmias, persistent nausea, confusion or visual changes require immediate evaluation.
Watch for digitalis toxicity and, when possible, check serum digoxin levels during the combination.
DailyMed/FDA (NIH/NLM) — approved Azithromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db52b91e-79f7-4cc1-9564-f2eee8e31c45 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Bumetanide-induced hypokalaemia increases digoxin toxicity.
Bumetanide is a loop diuretic that depletes potassium and magnesium. These electrolytes are critical in digitalis toxicity: hypokalaemia and hypomagnesaemia potentiate the arrhythmogenic effects of digoxin (aggravated Na+/K+-ATPase blockade), even at therapeutic digoxin levels. The risk is higher in elderly patients, in those with reduced renal function or with high diuretic doses. Monitor serum potassium and magnesium (keeping K+ ≥ 4.0 mEq/L), correct deficits, monitor the ECG and consider digoxin level monitoring.
Loop diuretic + digoxin: diuretic-induced hypokalaemia and hypomagnesaemia increase digitalis toxicity. Monitor electrolytes and digoxin levels.
Loop-diuretic potassium depletion sensitizes the myocardium to digoxin.
Potassium, digoxin levels, ECG.
Arrhythmia or bradycardia with nausea.
Monitor potassium and digoxin toxicity signs.
DailyMed (FDA) — approved Bumetanide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4a9229c8-89ba-423e-8e36-f56bc329ed38 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Calcitriol + digoxin: calcitriol-enhanced hypercalcaemia increases the risk of digitalis toxicity.
Calcitriol (active vitamin D) increases intestinal calcium absorption and can raise serum calcium. Hypercalcaemia combined with digoxin increases the risk of arrhythmias, especially in patients with renal impairment or on calcium supplements. Digitalis toxicity can occur at digoxin levels that would be safe with normal serum calcium. Monitor serum calcium during calcitriol treatment (especially with calcium supplementation or kidney disease), watch for digitalis toxicity signs and adjust accordingly.
Calcitriol raises serum calcium and hypercalcaemia increases digitalis toxicity (arrhythmias). Monitor serum calcium and toxicity signs.
Calcitriol increases calcium absorption; hypercalcaemia sensitises the myocardium to digoxin.
Serum calcium, renal function, ECG.
Nausea, arrhythmias, altered colour vision, confusion.
Monitor serum calcium and signs of digoxin toxicity; adjust digoxin dose if needed.
DailyMed (FDA) — approved Calcitriol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8465337c-86ca-ea9d-e053-2991aa0ab167 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Digoxin + vitamin D3: vitamin D-induced hypercalcaemia may increase digoxin toxicity.
Digitalis toxicity is potentiated by electrolyte disturbances, including hypercalcaemia (and hypokalaemia and hypomagnesaemia). Vitamin D3, especially at high doses or with simultaneous calcium supplementation, can raise serum calcium and increase myocardial sensitivity to digoxin, with risk of arrhythmias. In digitalised patients starting vitamin D (or increasing the dose), monitor serum calcium and signs of digitalis toxicity (nausea, bradycardia, arrhythmias, visual disturbances) and consider measuring digoxin levels; correct any hypercalcaemia promptly.
Digoxin + vitamin D3: vitamin D-induced hypercalcaemia may increase digitalis toxicity.
Vitamin D increases calcium absorption; in digitalised patients hypercalcaemia sensitises the myocardium.
Serum calcium and ECG.
Nausea, arrhythmias, confusion.
Monitor serum calcium and signs of digoxin toxicity, especially when thiazides are also used.
DailyMed (FDA) — approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 ; approved Cholecalciferol (vitamin D3) label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3822c324-e22a-4ac4-ac1c-9b63983b516a — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Digoxin + calcium: hypercalcaemia potentiates digoxin toxicity.
Calcium increases myocardial contractility and, at high concentrations, sensitises the heart to digoxin, increasing the risk of arrhythmias (including premature beats and ventricular tachycardias). Rapid intravenous calcium administration in digitalised patients is particularly dangerous. In patients on digoxin taking oral calcium supplements, monitor serum calcium and ECG, use the lowest effective calcium dose and correct any hypercalcaemia; also watch for signs of digitalis toxicity. The combination is safe with normal serum calcium, but the toxicity threshold falls with hypercalcaemia.
Digoxin + calcium: hypercalcaemia potentiates digitalis toxicity. Monitor ECG.
Calcium increases myocardial contractility and sensitises the heart to digoxin; intravenous calcium may precipitate arrhythmias.
Serum calcium, ECG, symptoms of digoxin toxicity.
Nausea, arrhythmias, confusion, altered colour vision.
Monitor serum calcium and signs of digoxin toxicity.
DailyMed (FDA) — approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 ; approved Calcium carbonate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=348d3dfa-6a52-4583-96e3-83c4bf2df45b — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Digoxin + magnesium: electrolyte imbalance with risk of arrhythmias.
Digitalis toxicity is potentiated by hypomagnesaemia (and hypokalaemia); conversely, hypermagnesaemia — which can occur with rapid infusion or renal impairment — depresses cardiac conduction and can worsen atrioventricular block in patients on digoxin. In digitalised patients, keep serum magnesium and potassium in the normal range, correct deficits (magnesium is even used in the treatment of digitalis toxicity with hypomagnesaemia) and, if IV magnesium is given, infuse slowly with ECG and renal function monitoring.
Digoxin + magnesium: electrolyte imbalance (hypo/hypermagnesaemia) with risk of arrhythmias.
Hypomagnesaemia increases digoxin toxicity; intravenous magnesium sulfate is used in toxicity, but cardiac monitoring is required.
Serum magnesium and ECG.
Arrhythmias, weakness, tetany.
Monitor magnesium, potassium and heart rhythm.
DailyMed (FDA) — approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 ; approved Magnesium sulfate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a5a9f565-639c-4b22-b9e5-718bac7cfcf3 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
As hyperthyroidism is controlled, methimazole can increase digoxin levels in the blood. Your doctor may need to reduce the digoxin dose.
The approved methimazole label (DailyMed) documents that serum digoxin levels may increase when a hyperthyroid patient on a stable digoxin regimen becomes euthyroid, recommending a digoxin dose reduction. Hyperthyroidism increases digoxin renal clearance and distribution; as the thyroid is controlled, clearance normalises and levels rise.
Serum digoxin levels may rise when a stabilised hyperthyroid patient becomes euthyroid; a digoxin dose reduction may be needed.
Normalisation of digoxin clearance with the euthyroid state, raising serum levels.
Digoxin levels, ECG and digestive/visual symptoms.
Persistent nausea, yellow/green vision, palpitations, bradycardia — assess digoxin toxicity.
Watch digoxin levels and signs of toxicity (nausea, colour vision, arrhythmias) as the patient reaches the euthyroid state.
DailyMed/FDA (NIH/NLM) — approved Methimazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b53f84ac-4263-478c-883d-aca7ab44fef5 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4 ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Epinephrine + digoxin: risk of arrhythmias (myocardial sensitisation).
Digoxin sensitises the myocardium to sympathetic stimulation: epinephrine, by stimulating beta and alpha receptors, increases automaticity and can precipitate ventricular arrhythmias, including ventricular tachycardia, in digitalised patients. The risk is higher with hypokalaemia (which digoxin itself favours) and with high epinephrine doses. This combination arises mainly in emergencies (cardiac arrest, anaphylaxis) or in patients with advanced heart failure. Monitor the ECG during administration, correct electrolytes (especially potassium and magnesium) and use the lowest effective epinephrine doses.
Epinephrine + digoxin: increased risk of ventricular arrhythmias (digoxin sensitises the myocardium to beta-adrenergic stimulation). Use with caution and monitor the ECG.
Both increase myocardial automaticity; potentiated hypokalaemia increases arrhythmia risk.
ECG and serum potassium.
Arrhythmias, palpitations, hypokalaemia.
Monitor heart rhythm and potassium in cardiac patients.
DailyMed (FDA) — approved Epinephrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5726eeca-db88-ba8e-e063-6294a90a927d ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Chloroquine can raise Digoxin levels, with a risk of digoxin toxicity.
Chloroquine inhibits P-glycoprotein and can reduce digoxin elimination, raising its plasma concentrations and the risk of digitalis toxicity. Reports exist of increased digoxin levels with concomitant chloroquine. Monitor digoxin levels and the ECG when chloroquine is started (especially in prolonged treatment, such as lupus or rheumatoid arthritis) and watch for digitalis toxicity signs, adjusting the digoxin dose if needed.
Chloroquine can inhibit P-glycoprotein and raise digoxin levels. Monitor digoxin levels during antimalarial treatment.
Inhibition of renal P-glycoprotein, reducing Digoxin excretion.
Digoxin level, ECG and renal function.
Nausea, vomiting, visual disturbances, bradycardia, arrhythmias.
Monitor digoxin levels and signs of toxicity; reduce the dose if needed.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Corticosteroid + digoxin: induced hypokalaemia increases digoxin toxicity.
Dexamethasone has mild mineralocorticoid activity that, at high doses or with prolonged use, can cause hypokalaemia and sodium/water retention. Hypokalaemia potentiates digitalis toxicity (ventricular arrhythmias, even at therapeutic digoxin levels), and fluid retention can decompensate the heart failure that prompted digoxin. Monitor serum potassium (keep ≥ 4.0 mEq/L) and weight, watch for decompensation and digitalis toxicity signs, and adjust accordingly.
Corticosteroids + digoxin: steroid-induced hypokalaemia increases digitalis toxicity; sodium/water retention may worsen heart failure. Monitor electrolytes.
Corticosteroid-associated potassium loss sensitises the myocardium to digoxin.
Serum potassium and ECG.
Nausea, arrhythmias, confusion, altered colour vision.
Monitor potassium and signs of digoxin toxicity.
DailyMed (FDA) — approved Dexamethasone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7cbd9005-7df2-47ee-adb3-7244c1c69bc3 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Erythromycin may raise plasma Digoxin levels, with a risk of digitalis toxicity (arrhythmias, nausea, visual disturbances).
Erythromycin raises digoxin concentrations through two mechanisms: P-glycoprotein inhibition (reduces intestinal and renal digoxin excretion) and elimination of the gut bacterial flora that metabolises digoxin to inactive metabolites. Studies show 40–100% increases in digoxin levels in patients treated with erythromycin, with a risk of digitalis toxicity. Monitor digoxin levels and the ECG during and after the antibiotic course, watch for toxicity symptoms and reduce the digoxin dose if needed.
Erythromycin inhibits P-gp and reduces the flora that inactivates digoxin, potentially raising its levels. Monitor for digitalis toxicity signs.
Erythromycin inhibits P-glycoprotein and CYP3A4, reducing Digoxin elimination and increasing its effect; electrolyte disturbances (hypokalemia) may potentiate digitalis toxicity.
Watch for bradycardia, arrhythmias, nausea, anorexia, visual disturbances and potassium levels.
Arrhythmias, marked bradycardia, persistent nausea or blurred vision require urgent evaluation and a digoxin level.
Monitor serum digoxin levels and signs of toxicity; a digoxin dose reduction or an alternative macrolide may be needed.
DailyMed/FDA (NIH/NLM) — approved Erythromycin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=49b3ca93-43cc-439c-8f5d-e3ea2e87ad2f ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Flecainide may raise digoxin by up to about 20%.
Flecainide and digoxin have additive effects on atrioventricular conduction, with a risk of AV block, and flecainide can slightly raise digoxin concentrations (possible inhibition of efflux transport). The combination is used in cardiology (e.g. control of atrial arrhythmias), but requires vigilance: monitor the ECG (PR interval, QRS duration), digoxin levels and signs of toxicity of both (flecainide can be proarrhythmic and digoxin causes arrhythmias at high levels).
Flecainide + digoxin: flecainide can slightly raise digoxin levels and both depress AV conduction. Monitor ECG and digoxin levels.
Flecainide slightly reduces renal clearance of digoxin, chiefly in the elderly and renal impairment.
Digoxin levels, heart rate, gastrointestinal symptoms.
Nausea, bradycardia or arrhythmia.
Monitor digoxin levels and signs of toxicity.
DailyMed (FDA) — approved Flecainide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=74c1eb2a-a37f-4f33-86bf-51e0d1d0c2bc ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Hydroxychloroquine raises Digoxin levels — risk of digoxin toxicity.
Hydroxychloroquine, like chloroquine, can inhibit P-glycoprotein and reduce digoxin elimination, raising its concentrations and the risk of digitalis toxicity. The interaction is most relevant in patients with lupus or rheumatoid arthritis on prolonged treatment, in whom the effect can manifest over weeks. Monitor digoxin levels and the ECG when hydroxychloroquine is started or adjusted and watch for digitalis toxicity signs (nausea, bradycardia, arrhythmias, visual disturbances).
Hydroxychloroquine can inhibit P-gp and raise digoxin levels. Monitor digoxin levels in prolonged treatment.
P-glycoprotein inhibition, reducing renal Digoxin excretion.
Digoxin level, ECG and renal function.
Nausea, visual disturbances, bradycardia.
Monitor digoxin levels; adjust the dose if needed.
DailyMed/FDA (NIH/NLM) — approved Hydroxychloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34496b43-05a2-45fb-a769-52b12e099341 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Indapamide-induced hypokalaemia raises digoxin toxicity.
Indapamide is a thiazide-like diuretic that depletes potassium and magnesium. Hypokalaemia potentiates digoxin toxicity (ventricular arrhythmias, even at therapeutic levels), especially in elderly hypertensive patients who frequently use the combination. Monitor serum potassium during treatment (keep ≥ 4.0 mEq/L), correct deficits, monitor the ECG and consider digoxin level monitoring if toxicity symptoms are suspected.
Thiazide-like diuretic + digoxin: diuretic-induced hypokalaemia increases digitalis toxicity. Monitor electrolytes.
The thiazide-like effect depletes potassium, sensitizing the myocardium to digoxin.
Potassium, ECG, GI symptoms.
Arrhythmia or bradycardia with nausea.
Monitor potassium and digoxin toxicity signs.
DailyMed (FDA) — approved Indapamide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=59cd3331-7afe-432a-8b50-39533fd5f392 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Itraconazole raises Digoxin concentrations, with a risk of digitalis toxicity.
Itraconazole is a potent P-glycoprotein inhibitor, reducing intestinal and renal digoxin excretion and raising its plasma concentrations — studies show 50–100% increases. The risk of digitalis toxicity (nausea, arrhythmias, visual disturbances) is significant. Monitor digoxin levels when itraconazole is started, reduce the digoxin dose if needed and watch the ECG and toxicity symptoms during and after antifungal treatment.
Itraconazole inhibits P-gp and can raise digoxin levels. Monitor digoxin levels and reduce the dose if needed.
P-glycoprotein inhibition by itraconazole reduces digoxin elimination.
Digoxin levels, ECG, gastrointestinal and visual symptoms.
Nausea, vomiting, arrhythmias, yellow/green vision.
Monitor digoxin levels and clinical signs; reduce the digoxin dose if needed (especially the elderly and renal impairment).
DailyMed/FDA (NIH/NLM) — approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Metoclopramide may reduce digoxin absorption and, in some patients, delay its therapeutic effect.
Metoclopramide accelerates gastric emptying and intestinal transit, which can increase the rate and extent of digoxin absorption (especially slow-release formulations) and transiently raise plasma levels. The effect is usually modest, but relevant in patients with borderline levels or reduced renal function. Monitor digoxin levels when metoclopramide is started or stopped and watch for digitalis toxicity signs; separate dosing when possible.
Metoclopramide accelerates gastric emptying and can increase digoxin absorption and levels. Monitor digoxin levels in stable patients.
Metoclopramide-induced faster intestinal transit reduces digoxin absorption time.
Monitor the antiarrhythmic/rate-control response and heart failure symptoms.
Loss of rhythm/heart failure control.
Monitor clinical response and consider dose adjustment or an alternative schedule.
DailyMed (FDA) — approved Metoclopramide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d31d815-50fa-4e78-8ebd-affc2514ce78 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Midodrine may potentiate digoxin bradycardia.
Midodrine (alpha-1 agonist) increases reflex vagal tone and digoxin has negative chronotropic and dromotropic effects: the combination can cause marked bradycardia and conduction blocks, especially in elderly patients with sinus node dysfunction. Digoxin itself also increases automaticity at toxic levels, so the ECG should be monitored. Monitor heart rate and ECG, use the lowest effective midodrine doses and watch for hypoperfusion symptoms (dizziness, syncope) and digitalis toxicity signs.
Midodrine + digoxin: additive negative chronotropic effect (bradycardia) and arrhythmia risk. Monitor heart rate and ECG.
Midodrine (alpha-1 agonist) reflexively lowers heart rate; digoxin also slows AV conduction.
Heart rate, BP, bradycardia symptoms.
Symptomatic bradycardia or supine hypertension.
Watch heart rate and blood pressure.
DailyMed (FDA) — approved Midodrine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=79b712a3-be12-4ea6-ac42-742826685ae5 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Propafenone raises digoxin levels, potentiating digitalis toxicity.
Propafenone raises digoxin concentrations (inhibition of efflux transport, with documented 30–80% increases) and, as a class 1C antiarrhythmic, has conduction-depressant effects that add to those of digoxin (AV block risk). The combination is common in atrial fibrillation. Monitor digoxin levels when propafenone is started (reducing the digoxin dose if needed), watch the ECG (PR, QRS, rate) and symptoms of toxicity of both drugs.
Propafenone can raise digoxin levels and both depress AV conduction. Monitor digoxin levels, ECG and toxicity signs.
Propafenone reduces digoxin renal clearance; largest effect at high doses.
Digoxin levels, bradycardia, GI symptoms.
Arrhythmia, nausea, confusion or lethargy.
Consider digoxin reduction and monitor levels/ECG.
DailyMed (FDA) — approved Propafenone label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2ecd6452-ccc3-493f-9a4a-69f0fbf67a42 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Quinine markedly raises Digoxin levels — high risk of digoxin toxicity.
Quinine is a potent P-glycoprotein inhibitor: it reduces renal and intestinal digoxin excretion and can raise its concentrations by 50–100%, with a significant risk of digitalis toxicity. Studies at therapeutic quinine doses show substantial increases in digoxin levels. Monitor digoxin levels when quinine is started (reducing the digoxin dose by about 30–50%), watch the ECG and toxicity symptoms (nausea, arrhythmias, visual disturbances) during and after antimalarial treatment.
Quinine inhibits P-gp and can markedly raise digoxin levels. Monitor digoxin levels and reduce the digoxin dose.
P-glycoprotein inhibition and reduced Digoxin volume of distribution.
Digoxin level, ECG and renal function.
Nausea, vomiting, visual disturbances, bradycardia, arrhythmias.
Monitor digoxin levels and the ECG; reduce the Digoxin dose if needed.
DailyMed/FDA (NIH/NLM) — approved Quinine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1f32f05c-a215-40be-b951-e41a7b54a8a0 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Rifampin lowers Digoxin levels (P-glycoprotein induction) — risk of losing control of heart failure or atrial fibrillation.
Rifampicin is a potent P-glycoprotein inducer: it increases transporter expression and accelerates digoxin elimination, reducing its plasma concentrations. The effect can decrease digoxin efficacy (loss of rate control in atrial fibrillation or of heart failure control), sometimes requiring a dose increase. The interaction is particularly relevant in tuberculosis treatment in cardiac patients. Monitor digoxin levels when rifampicin is started and stopped, adjust the digoxin dose as needed and re-evaluate after discontinuation (levels may rise when the inducing effect fades).
Rifampicin induces P-gp and can REDUCE digoxin levels, with loss of efficacy. Monitor digoxin levels and adjust the dose.
Induction of the P-glycoprotein transporter that eliminates Digoxin.
Digoxin levels, heart rate, heart-failure signs.
Worsening dyspnoea, tachyarrhythmias.
Monitor digoxin levels and clinical signs; adjust the dose.
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
The combination raises the risk of bradycardia and AV-node dysfunction.
Sotalol combines beta blockade (negative chronotropic and dromotropic effects) with class III activity (QT prolongation): with digoxin, the effects on heart rate and AV conduction add up, increasing the risk of bradycardia and block. Hypokalaemia/hypomagnesaemia (which digoxin can favour) potentiates sotalol torsades de pointes risk. This combination arises in atrial fibrillation, requiring ECG monitoring (rate, PR, QT), electrolytes and renal function, with dose adjustment.
Sotalol + digoxin: additive bradycardia and AV block; sotalol prolongs the QT and digoxin increases the arrhythmia risk. Monitor ECG and electrolytes.
Sotalol and digoxin depress AV conduction; sotalol also prolongs the QT.
Heart rate, ECG (PR/QT interval).
High-degree AV block, syncope or severe bradycardia.
Monitor heart rate and ECG; titrate with caution.
DailyMed (FDA) — approved Sotalol label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9a36d95c-6e93-4e57-befe-b5274f359244 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Sucralfate may reduce digoxin absorption, decreasing its effect.
Sucralfate forms a viscous gel that binds several drugs in the gastrointestinal tract, including digoxin, reducing its absorption and efficacy. The interaction is avoidable by separating doses: give digoxin at least 2 hours before sucralfate (some sources recommend longer). Separate the administrations, monitor the clinical response (rate control, heart failure signs) and, in stable patients with known levels, consider checking digoxin levels after sucralfate is introduced.
Sucralfate binds digoxin in the GI tract and reduces its absorption. Separate dosing by 2 hours and monitor the clinical response.
Sucralfate binding to digoxin in the gut reduces its bioavailability.
Monitor heart rate and heart failure symptoms.
Loss of rhythm/heart failure control.
Separate administration times (2 hours) and monitor levels/response.
DailyMed (FDA) — approved Sucralfate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e781cc0-24ec-4028-8262-dcef9873ea1f ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Voriconazole may raise Digoxin concentrations, with a risk of digitalis toxicity.
Voriconazole inhibits P-glycoprotein and can reduce digoxin elimination, raising its concentrations and the risk of digitalis toxicity. The voriconazole label recommends monitoring digoxin levels when they are co-administered. The interaction is particularly relevant in immunocompromised patients with invasive fungal infections, often on multiple drugs. Monitor digoxin levels when voriconazole is started and stopped, watch the ECG and digitalis toxicity symptoms and adjust the digoxin dose if needed.
Voriconazole inhibits P-gp and can raise digoxin levels. Monitor digoxin levels and toxicity signs.
Possible P-glycoprotein and metabolic inhibition, reducing digoxin elimination.
Digoxin levels, ECG, gastrointestinal and visual symptoms.
Nausea, vomiting, arrhythmias, xanthopsia.
Monitor digoxin levels and clinical signs; reduce the dose if needed.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5886e233-b2da-4acb-be05-9bf40fb8e7f4
Dietary fibre, such as wheat bran, may adsorb digoxin and reduce its oral absorption.
Separate digoxin intake from high-fibre meals by at least 2 hours.
EMC-UK (MHRA) — approved Digoxin SmPC: https://www.medicines.org.uk/emc/product/5463/smpc
Hypokalaemia increases myocardial sensitivity to digoxin and the risk of arrhythmias, including digoxin toxicity.
Correct potassium before and during treatment; monitor ECG and digoxin levels.
EMC-UK (MHRA) — approved Digoxin SmPC: https://www.medicines.org.uk/emc/product/5463/smpc
Digoxin crosses the placenta; data in pregnancy do not indicate teratogenicity, but the maternal dose may need adjustment.
Use if clinically indicated, with serum level monitoring and dose adjustment.
Digoxin is excreted into breast milk in small amounts, compatible with breastfeeding.
No specific additional contraception is required in chronic therapy.
EMC-UK (MHRA) — approved Digoxin SmPC: https://www.medicines.org.uk/emc/product/5463/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Cardiac glycoside: increases the force and velocity of myocardial systolic contraction (positive inotropy), slows the heart rate (negative chronotropy) and decreases conduction velocity through the atrioventricular node. Peak effect of tablets occurs 2 to 6 hours after dosing.
All of digoxin actions are mediated through inhibition of Na-K-ATPase: it increases intracellular calcium availability in the myocardium and conduction system, stimulates the parasympathetic system (effects on the sino-atrial and atrioventricular nodes) and reduces catecholamine reuptake.
After oral administration, peak serum concentrations occur in 1 to 3 hours; tablet absorption is 60 to 80% (absolute bioavailability). Meals slow absorption without changing the total amount absorbed; bran fibre may reduce it. Plasma protein binding is about 25% and the volume of distribution is large (475 to 500 L).
Only a small percentage (about 13%) of a dose is metabolised; metabolism does not depend on cytochrome P450. Digoxin is a substrate of P-glycoprotein. About 50 to 70% of a dose is excreted unchanged in urine, in proportion to creatinine clearance.
The elimination half-life is 1.5 to 2 days in volunteers with normal renal function, prolonging to 3.5 to 5 days in anuric patients. Dialysis removes digoxin ineffectively.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
