Summary

Verapamil significantly increases ticagrelor plasma concentrations through CYP3A4 inhibition, potentially leading to enhanced antiplatelet effects and increased bleeding risk. This interaction requires careful monitoring and possible dose adjustments when these medications are used concurrently.

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. Verapamil is a calcium channel blocker primarily used to treat hypertension, angina, and certain cardiac arrhythmias. Both medications are commonly prescribed in cardiovascular patients, making their potential interaction clinically relevant.

Mechanism of Interaction

The interaction between ticagrelor and verapamil occurs through inhibition of the CYP3A4 enzyme system. Verapamil is a moderate CYP3A4 inhibitor, while ticagrelor is primarily metabolized by CYP3A4. When verapamil inhibits this enzyme, it reduces ticagrelor's metabolism, leading to increased plasma concentrations of both ticagrelor and its active metabolite. This results in enhanced antiplatelet activity and prolonged drug effects.

Risks and Symptoms

The primary clinical risk of this interaction is significantly increased bleeding potential due to enhanced antiplatelet effects. Patients may experience prolonged bleeding times, increased risk of spontaneous bleeding, and more severe bleeding complications from minor trauma or procedures. The interaction may also increase the risk of ticagrelor-related side effects such as dyspnea, bradycardia, and ventricular pauses. Studies suggest verapamil can increase ticagrelor exposure by approximately 2.3-fold.

Management and Precautions

When concurrent use is necessary, consider reducing the ticagrelor dose and implement enhanced bleeding monitoring. Regular assessment of platelet function, complete blood counts, and clinical signs of bleeding is recommended. Patients should be educated about bleeding precautions and advised to report any unusual bleeding or bruising. Alternative calcium channel blockers with less CYP3A4 inhibition potential, such as amlodipine, may be considered. If bleeding occurs, temporary discontinuation of ticagrelor may be necessary. Healthcare providers should weigh the cardiovascular benefits against bleeding risks on an individual patient basis.

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.

Verapamil interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided while taking verapamil 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 verapamil's blood pressure-lowering effects and increase the risk of dizziness, fainting, and falls. High-fiber foods or fiber supplements may reduce verapamil absorption when taken at the same time, so it's recommended to separate their administration by at least 2 hours.