Summary

Itraconazole significantly increases digoxin blood levels by inhibiting both CYP3A4 metabolism and P-glycoprotein transport. This interaction can lead to digoxin toxicity and requires careful monitoring and potential dose adjustments.

Introduction

Digoxin is a cardiac glycoside primarily used to treat heart failure and certain arrhythmias by increasing cardiac contractility and controlling heart rate. Itraconazole is a triazole antifungal medication used to treat various fungal infections, including systemic mycoses and dermatophyte infections. Both medications are commonly prescribed, making their potential interaction clinically significant.

Mechanism of Interaction

Itraconazole inhibits digoxin elimination through two primary mechanisms. First, it inhibits the CYP3A4 enzyme system responsible for digoxin metabolism in the liver and intestines. Second, itraconazole blocks P-glycoprotein, a transport protein that normally pumps digoxin out of cells and facilitates its renal elimination. This dual inhibition results in decreased digoxin clearance and significantly elevated plasma concentrations, potentially increasing levels by 70-100%.

Risks and Symptoms

The primary risk of this interaction is digoxin toxicity, which can manifest as cardiac arrhythmias, including bradycardia, heart block, and potentially fatal ventricular arrhythmias. Patients may also experience gastrointestinal symptoms such as nausea, vomiting, and loss of appetite, as well as neurological effects including confusion, visual disturbances, and fatigue. The narrow therapeutic index of digoxin makes even modest increases in blood levels potentially dangerous, particularly in elderly patients or those with kidney disease.

Management and Precautions

When concurrent use is necessary, reduce the digoxin dose by approximately 50% before starting itraconazole. Monitor digoxin serum levels closely, checking levels 1-2 weeks after initiating itraconazole and adjusting doses accordingly. Target therapeutic digoxin levels should be maintained between 1.0-2.0 ng/mL. Monitor patients for signs of digoxin toxicity including cardiac symptoms, gastrointestinal effects, and neurological changes. Consider alternative antifungal agents with less interaction potential, such as fluconazole or terbinafine, when clinically appropriate. Regular ECG monitoring may be warranted in high-risk patients.

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.

Itraconazole interactions with food and lifestyle

Itraconazole should be taken with food to enhance absorption and bioavailability. The capsule formulation requires an acidic environment for optimal absorption, so it should be taken with a full meal or acidic beverage. Avoid taking itraconazole with antacids, H2 blockers, or proton pump inhibitors as these reduce stomach acid and significantly decrease drug absorption. Grapefruit juice should be avoided as it can increase itraconazole levels and risk of side effects. Alcohol should be used with caution as both itraconazole and alcohol can affect liver function.