Cardiac glycosides (digitalis)
ATC code: C01AA05 (Digoxin)
Brand names
Lanoxin, Digox
Inhibits cardiomyocyte Na+/K+-ATPase. Rising intracellular sodium drives intracellular calcium up via the Na+/Ca2+ exchanger, enhancing contractility (positive inotropic effect). Simultaneously increases vagal tone, slowing AV conduction and lowering heart rate in atrial fibrillation. Narrow therapeutic window – target 0.5–0.9 ng/mL in HFrEF. Eliminated predominantly by the kidneys. A P-glycoprotein substrate – P-gp inhibitors (amiodarone, verapamil, clarithromycin, itraconazole) raise digoxin levels.
Second line
Per AF 2024, digoxin is an option for ventricular rate control in sedentary patients, HFrEF, or intolerance to beta-blockers and non-dihydropyridine calcium antagonists. First-line in AF with preserved EF: beta-blockers (metoprolol, bisoprolol, carvedilol) and verapamil/diltiazem when beta-blockade is contraindicated. Digoxin works at rest but does not control rate during exertion – monotherapy is insufficient in active patients. Often combined with a beta-blocker in HFrEF.
Individual decision
Per HF 2021, digoxin (class IIb, level B) is considered in HFrEF patients in sinus rhythm with persisting symptoms after full four-pillar therapy. Digoxin does not affect overall mortality (DIG trial 1997) but reduces decompensation hospitalisations. Target serum level 0.5–0.9 ng/mL; levels above 1.2 ng/mL increase mortality. In AF with HF, digoxin remains relevant for rate control in sedentary patients and in those with hypotension.
HFrEF with persistent symptoms on optimal therapy: ACEi/ARNI + beta-blocker + MRA + SGLT2i.
Individual decision
In adults with paroxysmal SVT, digoxin is rarely used for prophylaxis – international guidelines ( 2019 on SVT, /HRS 2015) prefer beta-blockers and non-dihydropyridine calcium antagonists, and propafenone or flecainide in WPW. In infants, digoxin remains acceptable for long-term prophylaxis of AV nodal reciprocating tachycardia. IV adenosine is the agent of choice for acute conversion.
Mostly paediatric long-term prophylaxis of SVT paroxysms in infants.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Digoxin is a cardiac glycoside. It is prescribed for heart failure with reduced ejection fraction (when standard therapy is ineffective) and for rate control in atrial fibrillation ( 2024). In alt-cardiology, digoxin is sometimes promoted as a mild cardiotonic for older adults to support the heart. No clinical studies of prophylactic use outside HF or AF exist, and such prescription is dangerous. Digoxin has a narrow therapeutic index – the gap between therapeutic and toxic doses is small. Signs of toxicity: nausea, visual disturbances (yellow-tinted vision), arrhythmias (especially with hypokalemia). Risk is higher in older adults and with renal impairment. If digoxin was prescribed outside heart failure or AF, consider seeking a second opinion.
20 pairs found. Sorted from critical to minor.
Mechanism
Amiodarone blocks P-glycoprotein in the intestine and renal tubules – the main dabigatran-style clearance route of digoxin. Digoxin plasma levels rise 1.7- to 2.5-fold. The narrow therapeutic window of digoxin turns any rise into a risk of acute toxicity.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. In older adults: confusion, dizziness. Symptoms appear 1–2 weeks after starting amiodarone.
Management
When amiodarone is started, halve the digoxin dose immediately. Measure digoxin level after 1 week (target 0.5–0.9 ng/mL in heart failure). Check potassium and magnesium monthly: hypokalaemia worsens digoxin toxicity.
Sources
Mechanism
Amiodarone blocks the P-glycoprotein transporter and renal tubular secretion of digoxin. Digoxin plasma levels rise 1.5- to 2-fold. The narrow therapeutic window converts any rise into acute toxicity risk.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Older adults: confusion, dizziness. Symptoms appear within 1–2 weeks of co-administration.
Management
When amiodarone starts, halve the digoxin dose. Measure digoxin level at 1 week (target 0.5–0.9 ng/mL in heart failure). Check potassium and magnesium monthly: low values worsen digoxin toxicity.
Mechanism
Clarithromycin blocks intestinal P-glycoprotein and suppresses gut flora that partly inactivates digoxin. Digoxin plasma levels rise 1.7- to 2.5-fold.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Older adults: confusion, dizziness. Symptoms appear within 1–2 weeks of co-administration.
Management
During clarithromycin therapy, reduce digoxin by 50%; check level at 5–7 days. Alternative antibiotics without P-glycoprotein block: azithromycin or doxycycline.
Mechanism
Diltiazem blocks intestinal P-glycoprotein – a key digoxin absorption route. Digoxin plasma levels rise by 20–30%. Diltiazem also slows AV conduction.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Older adults: confusion, dizziness. Symptoms appear within 1–2 weeks of co-administration.
Management
When diltiazem starts, reduce digoxin by 25%; check level at 1 week. Alternatives: amlodipine (no P-glycoprotein effect) or a beta-blocker for rate control.
Mechanism
Dronedarone blocks intestinal P-glycoprotein – the main route of digoxin absorption and elimination. Digoxin plasma levels rise 1.7- to 2.5-fold. Dronedarone also enhances contractile and bradycardic effects.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Older adults: confusion, dizziness. Symptoms appear within 1–2 weeks of co-administration.
Management
When dronedarone starts, halve the digoxin dose; check level at 1 week. If sinus node or AV conduction symptoms appear, hold digoxin temporarily.
Mechanism
Additive slowing of atrioventricular (AV) conduction and lowered heart rate. In atrial fibrillation this synergistic ventricular rate control is standard; without atrial fibrillation, bradycardia and AV block risks rise.
Symptoms
Bradycardia (heart rate below 50/min), dizziness, syncope. ECG: first- to second-degree AV block, prolonged PR. Older patients: fatigue, weakness.
Management
The combination is appropriate in atrial fibrillation with preserved or reduced ejection fraction. Check pulse and ECG at 1 and 4 weeks. If pulse drops below 50 or second-degree AV block appears, reduce metoprolol; if symptoms persist, hold digoxin temporarily.
Sources
Mechanism
Verapamil blocks P-glycoprotein in the intestine and renal tubules – key digoxin clearance routes. Digoxin plasma levels rise by 50–75%. Verapamil also slows AV conduction.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Older adults: confusion, dizziness. Symptoms appear within 1–2 weeks of co-administration.
Management
When verapamil starts, reduce digoxin by 30–50%; check level at 1 week. Alternative calcium channel blocker without P-glycoprotein effect: amlodipine (for blood pressure control) or a beta-blocker.
Mechanism
High aspirin doses can reduce renal digoxin clearance via prostaglandin-dependent renal blood flow suppression. The effect is clinically significant at analgesic aspirin doses (above 1 g/day), not cardioprotective ones.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias at aspirin doses above 1 g/day.
Management
Cardioprotective aspirin doses are acceptable without adjustment. At high doses, check digoxin level at 1 week. For chronic analgesia on digoxin: paracetamol.
Mechanism
Atorvastatin blocks intestinal P-glycoprotein (one of the digoxin clearance routes). Digoxin plasma levels rise by about 20%.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias. Older patients: confusion.
Management
After starting atorvastatin, check digoxin level at 2–4 weeks. If it rises above target, reduce digoxin by 25%.
Mechanism
Macrolides suppress the gut bacteria Eggerthella lenta that inactivate digoxin. Digoxin plasma levels rise within days of co-administration.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias. Older patients: confusion.
Management
For short azithromycin courses (3–5 days), check digoxin level at 5–7 days. If it rises, temporarily reduce digoxin. Alternative antibiotics without gut flora effect: a cephalosporin or doxycycline.
Mechanism
Additive bradycardia and atrioventricular (AV) conduction slowing. Used in atrial fibrillation and heart failure for ventricular rate control.
Symptoms
Lower blood pressure, postural dizziness, fatigue. Older patients: fall risk. With additional antihypertensives: bradycardia (pulse below 60/min).
Management
Standard regimen for atrial fibrillation with rapid ventricular response and heart failure. Check pulse and ECG at 1 and 4 weeks. If pulse drops below 50/min or second-degree AV block appears, adjust dose.
Sources
Mechanism
Ciclosporin inhibits P-glycoprotein in gut and renal tubules, reducing digoxin clearance. Digoxin AUC rises by 50–100%; toxicity risk is substantial.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
On ciclosporin start, reduce digoxin dose by 25–50% and check levels at 5–7 days. Target: 0.5–0.8 ng/mL. In parallel, monitor potassium and creatinine (ciclosporin is nephrotoxic and raises hyperkalaemia risk).
Mechanism
In 10–15% of patients, gut flora (mainly Eubacterium lentum) metabolises part of digoxin to inactive products. Ciprofloxacin suppresses this flora — digoxin levels rise by 30–80% in those patients, increasing toxicity risk.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
For short ciprofloxacin courses (5–7 days), most patients need no adjustment. In older patients and chronic kidney disease, check digoxin level at 5–7 days after antibiotic start. With toxicity signs, reduce dose by 25%. Alternative antibiotics: a cephalosporin (minimal gut flora impact).
Sources
Mechanism
Furosemide is a loop diuretic that increases urinary loss of potassium and magnesium. Low serum potassium (hypokalaemia) and low magnesium increase digoxin binding to the cardiac sodium-potassium ATPase and intensify its toxicity even when digoxin plasma levels are within range. Furosemide does not change digoxin concentration directly – the danger is the electrolyte shift.
Symptoms
Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias ranging from premature beats to ventricular tachycardia. Confusion in older adults. Symptoms emerge once potassium falls below 3.5 mmol/L.
Management
Check serum potassium before starting the combination, again at 1–2 weeks, and every 1–3 months thereafter. Monitor magnesium in parallel. If potassium drops below 4 mmol/L in a digoxin patient, add a potassium-sparing diuretic (spironolactone, eplerenone) or oral potassium. Replete magnesium when levels are below 0.7 mmol/L.
Mechanism
Thiazide diuretic causes hypokalaemia and hypomagnesaemia, increasing myocardial sensitivity to digoxin. Arrhythmia risk rises, especially ventricular arrhythmias.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
On the combination, check potassium and magnesium every 2–4 weeks in the first 3 months, then every 3–6 months. If potassium falls below 4 mmol/L, add potassium supplements or a low-dose potassium-sparing diuretic (spironolactone). Thiazide alternatives in hypokalaemia: indapamide with potassium supplementation or a thiazide/potassium-sparing combination.
Sources
Mechanism
Rifampicin induces enterocyte P-glycoprotein. Digoxin bioavailability falls by 30%, levels drop — risking loss of rate control in atrial fibrillation or worsening of chronic heart failure.
Symptoms
Return of underlying disease: tachycardia in atrial fibrillation, dyspnoea and oedema in chronic heart failure. After rifampicin stops, digoxin levels may rise sharply.
Management
On the combination, check digoxin levels at 2 and 4 weeks after rifampicin start and 2 weeks after rifampicin stops. Digoxin dose is usually raised by 25–50% during rifampicin and returned to baseline afterward. In atrial fibrillation, consider adding a beta-blocker (bisoprolol, metoprolol) for rate control.
Sources
Mechanism
Spironolactone moderately inhibits P-glycoprotein; digoxin levels rise by 20–30%. Spironolactone metabolites also cross-react with immunoassay measurements of digoxin, falsely elevating reported values.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
On spironolactone start, reinterpret target digoxin concentration (rather than 0.5–0.9 ng/mL, aim for the lower boundary). Check potassium and creatinine every 2–4 weeks for the first 3 months. With toxicity signs, reduce digoxin by 25%.
Sources
Mechanism
Spironolactone moderately inhibits P-glycoprotein; digoxin levels rise by 20–30%. Spironolactone metabolites cross-react with immunoassays and falsely elevate digoxin readings.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
On spironolactone start, shift the target digoxin concentration toward the lower end of the range. Check potassium and creatinine every 2–4 weeks for the first 3 months. With toxicity signs, reduce digoxin by 25%.
Sources
Mechanism
Telmisartan moderately inhibits intestinal P-glycoprotein. Digoxin AUC rises by 20–50%, which may trigger toxicity, especially in older patients and in chronic kidney disease.
Symptoms
Nausea, vomiting, loss of appetite, confusion, yellow-green halos around lights, arrhythmia (bigeminy, AV block). Symptoms appear earlier in older patients and chronic kidney disease.
Management
On telmisartan start, check digoxin levels at 1–2 weeks. In significant chronic kidney disease (clearance below 50 mL/min), reduce digoxin by 25%. In older patients, target 0.5–0.8 ng/mL. Alternatives: losartan or valsartan, with less effect on P-glycoprotein.
Mechanism
No direct pharmacokinetic or pharmacodynamic interaction. Isolated reports of slight digoxin elevation in older patients, without clinical significance.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. In older patients on digoxin, watch for alprazolam sedation signs.
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Digoxin crosses the placenta. Use in pregnancy is acceptable on vital indications (foetal tachyarrhythmias – maternal oral digoxin). Standard care for foetal tachyarrhythmias in some centres.
Excreted in breast milk in small amounts. Compatible with breastfeeding per LactMed.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Digoxin is evaluated for the following indications with varying evidence strength: Atrial fibrillation: ventricular rate control (evidence tier B), Heart failure (evidence tier B), Supraventricular tachycardia (evidence tier C). See the full indication matrix with dosing and citations above on this page.
Common side effects of Digoxin (≥ 1 in 100): Nausea, vomiting, anorexia, Visual disturbance (yellow-green halos), Headache, dizziness, Weakness, fatigue, Arrhythmias: bradycardia, ectopy. See the Safety section for uncommon and serious reactions.
FDA category C. Digoxin crosses the placenta. Use in pregnancy is acceptable on vital indications (foetal tachyarrhythmias – maternal oral digoxin). Standard care for foetal tachyarrhythmias in some centres.
Excreted in breast milk in small amounts. Compatible with breastfeeding per LactMed.
Digoxin is contraindicated in: Digitalis toxicity; Second- or third-degree AV block without pacemaker; Hypertrophic obstructive cardiomyopathy (worsens outflow obstruction); WPW syndrome with atrial fibrillation (accessory pathway conduction risk); Ventricular tachycardia or fibrillation. Full list in the Safety section.
digoxin increases contractility but does not affect overall HF mortality. Modern HF foundation: ACEi/ARNI, beta-blocker, MRA, SGLT2i – these reduce mortality. Digoxin remains a useful adjunct for persistent symptoms.
in older patients and those with reduced eGFR, toxicity risk is high; target levels at the lower end 0.5–0.7 ng/mL. Prescription requires biochemistry and drug-level monitoring.