Summary

Ticagrelor significantly increases digoxin plasma concentrations by inhibiting P-glycoprotein-mediated efflux transport. This interaction can lead to elevated digoxin levels and potential toxicity, requiring careful monitoring and possible dose adjustments.

Introduction

Ticagrelor is a P2Y12 receptor antagonist used as an antiplatelet agent for preventing thrombotic cardiovascular events in patients with acute coronary syndromes or established coronary artery disease. Digoxin is a cardiac glycoside primarily used to treat heart failure and certain arrhythmias, particularly atrial fibrillation, by increasing cardiac contractility and controlling heart rate. Both medications are commonly prescribed in cardiovascular patients, making their potential interaction clinically relevant.

Mechanism of Interaction

The interaction between ticagrelor and digoxin occurs through inhibition of P-glycoprotein (P-gp), an efflux transporter protein. Ticagrelor acts as a P-glycoprotein inhibitor, reducing the active transport of digoxin out of cells, particularly in the kidneys and intestines. This inhibition decreases digoxin clearance and increases its bioavailability, resulting in elevated plasma digoxin concentrations. The effect is dose-dependent and can lead to a 1.5-fold increase in digoxin exposure when co-administered with standard ticagrelor doses.

Risks and Symptoms

The primary clinical risk of this interaction is digoxin toxicity due to elevated serum concentrations. Signs of digoxin toxicity include nausea, vomiting, visual disturbances, confusion, cardiac arrhythmias (particularly bradycardia, heart block, or ventricular arrhythmias), and potentially life-threatening cardiac complications. Elderly patients and those with renal impairment are at higher risk due to reduced digoxin clearance. The narrow therapeutic index of digoxin makes even modest increases in plasma levels clinically significant, potentially leading to serious adverse events.

Management and Precautions

When ticagrelor and digoxin are co-administered, close monitoring of digoxin serum levels is essential, with baseline levels obtained before starting ticagrelor. Consider reducing the digoxin dose by approximately 50% when initiating ticagrelor therapy. Monitor patients for signs and symptoms of digoxin toxicity, including cardiac rhythm changes, gastrointestinal symptoms, and neurological effects. Regular ECG monitoring and serum digoxin level checks should be performed, particularly during the first few weeks of combination therapy. Adjust digoxin dosing based on serum levels and clinical response, and consider alternative antiplatelet agents if digoxin toxicity becomes problematic.

Ticagrelor interactions with food and lifestyle

Ticagrelor should be taken with or without food as food does not significantly affect absorption. However, patients should avoid grapefruit juice as it may increase ticagrelor levels in the blood through CYP3A4 inhibition, potentially increasing bleeding risk. Alcohol consumption should be limited as it may increase the risk of bleeding when combined with ticagrelor. Patients should also be cautious with activities that may increase bleeding risk, such as contact sports or activities with high injury potential, due to ticagrelor's antiplatelet effects.

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.