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 increased digoxin bioavailability and decreased elimination, leading to elevated plasma concentrations that can persist for several days after diltiazem initiation.

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 being dose-dependent. Elderly patients and those with renal impairment are at higher risk due to reduced digoxin clearance. The interaction typically develops within 24-72 hours of diltiazem initiation but may take longer to resolve after discontinuation.

Management and Precautions

When co-prescribing these medications, reduce the digoxin dose by 25-50% when initiating diltiazem therapy. Monitor digoxin serum levels closely, checking levels 1-2 weeks after starting diltiazem and after any dose adjustments. Baseline digoxin levels should be obtained before diltiazem initiation. Watch for signs and symptoms of digoxin toxicity including gastrointestinal symptoms, neurological changes, and cardiac rhythm abnormalities. Consider alternative calcium channel blockers like amlodipine if appropriate, as they have less interaction potential. Regular monitoring of renal function, electrolytes (especially potassium and magnesium), and ECG changes is recommended throughout concurrent therapy.

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.