Summary

Azithromycin may increase digoxin serum concentrations, potentially leading to digoxin toxicity. This interaction occurs through inhibition of P-glycoprotein transport and alterations in gut flora that affect digoxin metabolism.

Introduction

Digoxin is a cardiac glycoside primarily used to treat heart failure and certain arrhythmias, particularly atrial fibrillation. It works by inhibiting the sodium-potassium ATPase pump, increasing cardiac contractility and slowing heart rate. Azithromycin is a macrolide antibiotic commonly prescribed for respiratory tract infections, skin infections, and sexually transmitted diseases. It works by binding to the 50S ribosomal subunit, inhibiting bacterial protein synthesis.

Mechanism of Interaction

The interaction between digoxin and azithromycin occurs through multiple mechanisms. Azithromycin can inhibit P-glycoprotein, a transport protein responsible for digoxin elimination from cells, particularly in the kidneys and intestines. This inhibition reduces digoxin clearance and increases serum concentrations. Additionally, azithromycin may alter intestinal flora that normally metabolize digoxin in some patients (approximately 10% of the population), further contributing to elevated digoxin levels. The macrolide structure of azithromycin is associated with these transport protein interactions.

Risks and Symptoms

The primary risk of this interaction is digoxin toxicity, which can manifest as cardiac arrhythmias, including bradycardia, heart block, or ventricular arrhythmias. Gastrointestinal symptoms such as nausea, vomiting, and loss of appetite may occur early in toxicity. Neurological effects including confusion, visual disturbances (yellow-green halos), and fatigue can also develop. The interaction is considered moderate to major in clinical significance, as digoxin has a narrow therapeutic index. Elderly patients and those with renal impairment are at higher risk for developing toxicity.

Management and Precautions

Close monitoring of digoxin serum levels is essential when azithromycin is co-administered. Baseline digoxin levels should be obtained before starting azithromycin, with follow-up levels checked 3-5 days after azithromycin initiation and again after completion of the antibiotic course. Consider reducing the digoxin dose by 25-50% during azithromycin therapy, particularly in elderly patients or those with renal impairment. Monitor patients for signs and symptoms of digoxin toxicity, including cardiac rhythm changes, gastrointestinal symptoms, and neurological effects. Alternative antibiotics should be considered when possible, especially for patients with elevated baseline digoxin levels or previous episodes of digoxin toxicity.

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.

Azithromycin interactions with food and lifestyle

Azithromycin can be taken with or without food. However, taking azithromycin with food may help reduce stomach upset in some patients. Antacids containing aluminum or magnesium should be avoided within 2 hours before or after taking azithromycin, as they may decrease the absorption of the medication. No significant interactions with alcohol have been established, but patients should use alcohol cautiously while taking any antibiotic due to potential effects on immune function and healing.