Digoxin

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.

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).

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.

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.

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%.

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%.

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.