Summary

Diltiazem significantly increases digoxin blood levels by inhibiting P-glycoprotein transport and reducing renal clearance. 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 atrial fibrillation by increasing cardiac contractility and controlling heart rate. Diltiazem is a non-dihydropyridine calcium channel blocker commonly prescribed for hypertension, angina, and certain arrhythmias. Both medications are frequently used in cardiovascular patients, making their interaction clinically significant.

Mechanism of Interaction

Diltiazem increases digoxin serum concentrations through multiple mechanisms. It inhibits P-glycoprotein, a transport protein responsible for digoxin efflux from cells and elimination through the kidneys and intestines. Additionally, diltiazem may reduce digoxin's renal clearance and potentially affect its hepatic metabolism. This results in decreased digoxin elimination and increased bioavailability, leading to elevated plasma concentrations that can reach toxic levels.

Risks and Symptoms

The primary risk of this interaction is digoxin toxicity, which can manifest as nausea, vomiting, visual disturbances, confusion, and potentially life-threatening cardiac arrhythmias including bradycardia, heart block, and ventricular arrhythmias. Studies show that diltiazem can increase digoxin levels by 20-50%, with the effect typically occurring within 24-72 hours of initiating diltiazem therapy. Elderly patients and those with kidney disease are at higher risk for toxicity.

Management and Precautions

When co-prescribing these medications, reduce the initial digoxin dose by 25-50% and monitor digoxin serum levels closely. Check digoxin levels within 1-2 weeks after starting diltiazem or changing its dose. Monitor patients for signs and symptoms of digoxin toxicity, including gastrointestinal symptoms, neurological changes, and cardiac rhythm abnormalities. Regular monitoring of kidney function, electrolytes (especially potassium and magnesium), and ECG is recommended. Consider alternative calcium channel blockers if clinically appropriate.

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.

Diltiazem interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking diltiazem as they can significantly increase blood levels of the medication, potentially leading to dangerous drops in blood pressure and heart rate. Alcohol consumption should be limited or avoided as it can enhance the blood pressure-lowering effects of diltiazem and increase the risk of dizziness, fainting, and falls. Patients should also be cautious when standing up quickly or engaging in activities requiring alertness, as diltiazem can cause dizziness and lightheadedness, especially when starting treatment or increasing the dose.