Summary

Amphotericin B can increase the risk of digoxin toxicity by causing electrolyte imbalances, particularly hypokalemia and hypomagnesemia. This interaction requires careful monitoring of electrolyte levels and digoxin concentrations to prevent potentially serious cardiac complications.

Introduction

Amphotericin B is a polyene antifungal medication used to treat serious systemic fungal infections, including invasive aspergillosis, candidiasis, and cryptococcosis. It works by binding to ergosterol in fungal cell membranes, causing cell death. Digoxin is a cardiac glycoside derived from the foxglove plant, primarily used to treat heart failure and certain arrhythmias like atrial fibrillation. It works by inhibiting the sodium-potassium ATPase pump, increasing intracellular calcium and improving cardiac contractility while slowing heart rate.

Mechanism of Interaction

The interaction between Amphotericin B and digoxin occurs through Amphotericin B's nephrotoxic effects, which can lead to significant electrolyte disturbances. Amphotericin B commonly causes hypokalemia (low potassium) and hypomagnesemia (low magnesium) by increasing renal losses of these electrolytes. These electrolyte imbalances enhance digoxin's binding to the sodium-potassium ATPase pump and increase myocardial sensitivity to digoxin's effects. Low potassium and magnesium levels predispose patients to digoxin toxicity even at therapeutic digoxin concentrations, as these electrolytes compete with digoxin for binding sites on the cardiac enzyme.

Risks and Symptoms

The primary risk of this interaction is increased digoxin toxicity, which can manifest as serious cardiac arrhythmias including ventricular tachycardia, heart block, and potentially fatal dysrhythmias. Patients may experience symptoms such as nausea, vomiting, visual disturbances (yellow-green halos), confusion, and cardiac symptoms like palpitations or bradycardia. The risk is particularly elevated in elderly patients, those with pre-existing kidney disease, or patients receiving higher doses of Amphotericin B. Additionally, Amphotericin B's nephrotoxic effects can reduce digoxin clearance, further contributing to elevated digoxin levels and toxicity risk.

Management and Precautions

Close monitoring is essential when these drugs are used concurrently. Electrolyte levels, particularly potassium and magnesium, should be checked frequently (at least twice weekly initially) and maintained within normal ranges through supplementation as needed. Digoxin levels should be monitored more frequently than usual, with consideration for dose reduction if levels become elevated. Renal function should be assessed regularly due to Amphotericin B's nephrotoxic potential. Consider using lipid formulations of Amphotericin B when possible, as they may have reduced nephrotoxicity. Patients should be educated about signs and symptoms of digoxin toxicity and advised to report any concerning symptoms immediately. Alternative antifungal agents should be considered if clinically appropriate to minimize interaction risks.

Amphotericin B interactions with food and lifestyle

Digoxin interactions with food and lifestyle

Digoxin has several important food and lifestyle interactions that patients should be aware of. High-fiber foods, including bran cereals and fiber supplements, can significantly reduce digoxin absorption and should be taken at least 2 hours apart from digoxin doses. St. John's wort, an herbal supplement, can decrease digoxin levels and reduce its effectiveness, so concurrent use should be avoided. Alcohol consumption can affect digoxin levels and increase the risk of side effects, particularly heart rhythm abnormalities. Patients should limit alcohol intake and discuss any alcohol use with their healthcare provider. Additionally, maintaining consistent dietary habits is important, as sudden changes in fiber intake or meal timing can affect digoxin absorption and blood levels. Patients should also be cautious with salt substitutes containing potassium, as changes in potassium levels can affect digoxin's effectiveness and safety.