Summary

The combination of arsenic trioxide and digoxin presents a significant drug interaction with increased risk of cardiac arrhythmias and digoxin toxicity. Both medications can affect cardiac conduction and electrolyte balance, requiring careful monitoring and potential dose adjustments.

Introduction

Arsenic trioxide is an antineoplastic agent primarily used in the treatment of acute promyelocytic leukemia (APL), belonging to the class of heavy metal compounds with anticancer properties. Digoxin is a cardiac glycoside derived from the foxglove plant, commonly prescribed for heart failure and atrial fibrillation to improve cardiac contractility and control heart rate. Both medications have narrow therapeutic windows and can significantly impact cardiac function.

Mechanism of Interaction

The interaction between arsenic trioxide and digoxin occurs through multiple mechanisms. Arsenic trioxide can cause electrolyte imbalances, particularly hypokalemia and hypomagnesemia, which increase myocardial sensitivity to digoxin and predispose to digoxin toxicity. Additionally, both drugs can prolong the QT interval through different pathways - arsenic trioxide by blocking potassium channels and digoxin by affecting sodium-potassium ATPase pumps. This dual effect significantly increases the risk of life-threatening arrhythmias, including torsades de pointes.

Risks and Symptoms

The primary clinical risks include increased digoxin toxicity manifesting as nausea, vomiting, visual disturbances, and potentially fatal cardiac arrhythmias. The combination significantly elevates the risk of QT interval prolongation, which can progress to torsades de pointes, ventricular fibrillation, and sudden cardiac death. Electrolyte disturbances caused by arsenic trioxide further amplify these risks by making the heart more susceptible to digoxin's toxic effects. Patients may experience enhanced bradycardia, heart block, or other conduction abnormalities.

Management and Precautions

Close monitoring is essential when these medications must be used concurrently. Obtain baseline and frequent ECGs to monitor QT interval and cardiac rhythm. Regular monitoring of serum electrolytes (potassium, magnesium, calcium) and digoxin levels is crucial, with prompt correction of any imbalances. Consider reducing digoxin dose and increasing monitoring frequency. Maintain serum potassium above 4.0 mEq/L and magnesium above 2.0 mg/dL. Discontinue both medications immediately if QTc exceeds 500 ms or if signs of digoxin toxicity appear. Alternative treatments should be considered when possible to avoid this high-risk combination.

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.