Summary

Azithromycin can significantly increase digoxin serum levels, potentially leading to digoxin toxicity. This interaction occurs through inhibition of P-glycoprotein transport and alteration of gut flora that metabolizes digoxin.

Introduction

Azithromycin is a macrolide antibiotic commonly prescribed for respiratory tract infections, skin infections, and sexually transmitted diseases. It works by inhibiting bacterial protein synthesis. Digoxin is a cardiac glycoside 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.

Mechanism of Interaction

The azithromycin-digoxin interaction occurs through multiple mechanisms. Azithromycin inhibits P-glycoprotein, a transport protein responsible for digoxin elimination from cells, leading to increased digoxin absorption and decreased renal clearance. Additionally, azithromycin can alter intestinal flora, reducing bacteria that normally metabolize digoxin in the gut. This dual mechanism can result in significantly elevated digoxin serum concentrations, with increases of 20-70% reported in clinical studies.

Risks and Symptoms

The primary risk of this interaction is digoxin toxicity, which can be life-threatening. Signs of digoxin toxicity include nausea, vomiting, visual disturbances (yellow-green halos), confusion, and cardiac arrhythmias such as bradycardia, heart block, or ventricular arrhythmias. Elderly patients and those with renal impairment are at higher risk due to reduced digoxin clearance. The interaction can persist for several days after azithromycin discontinuation due to the antibiotic's long half-life and prolonged tissue distribution.

Management and Precautions

Close monitoring is essential when co-administering these medications. Obtain baseline digoxin levels before starting azithromycin and monitor levels 3-5 days after initiation. Consider reducing digoxin dose by 25-50% when starting azithromycin. Monitor patients for signs of digoxin toxicity including cardiac symptoms, gastrointestinal effects, and neurological changes. Check electrolyte levels, particularly potassium and magnesium, as imbalances can increase digoxin toxicity risk. Consider alternative antibiotics when possible, especially for patients with narrow therapeutic windows or history of digoxin toxicity.

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.

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.