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.

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 and decreasing its renal elimination. This mechanism leads to increased digoxin absorption, reduced clearance, and elevated plasma concentrations. Studies have shown that ticagrelor can increase digoxin AUC by approximately 75% and peak concentrations by about 28%.

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 for developing toxicity. The narrow therapeutic index of digoxin makes this interaction clinically significant, as small increases in concentration can lead to adverse effects.

Management and Precautions

When ticagrelor and digoxin are used concurrently, close monitoring is essential. Measure baseline digoxin levels before initiating ticagrelor and monitor levels 1-2 weeks after starting combination therapy. Consider reducing the digoxin dose by 50% when initiating ticagrelor, with subsequent adjustments based on serum levels and clinical response. Monitor patients for signs and symptoms of digoxin toxicity, including cardiac rhythm changes, gastrointestinal symptoms, and neurological effects. Regular ECG monitoring and assessment of renal function are recommended. Healthcare providers should verify current digoxin levels and consider alternative antiplatelet agents if the interaction poses significant clinical risks.

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.