Summary

Diltiazem can significantly increase 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, particularly in patients with acute coronary syndromes or established coronary artery disease. Diltiazem is a non-dihydropyridine calcium channel blocker primarily used to treat hypertension, angina, and certain arrhythmias. Both medications are commonly prescribed in cardiovascular patients, making their potential interaction clinically relevant.

Mechanism of Interaction

The interaction between ticagrelor and diltiazem occurs through inhibition of the cytochrome P450 3A4 (CYP3A4) enzyme system. Diltiazem is a moderate CYP3A4 inhibitor, while ticagrelor is primarily metabolized by CYP3A4. When diltiazem inhibits this enzyme, it reduces the metabolism of ticagrelor, 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 an increased potential for bleeding complications due to enhanced antiplatelet effects. Patients may experience prolonged bleeding times, increased risk of major bleeding events, and heightened susceptibility to bruising. The interaction may also lead to other ticagrelor-related adverse effects such as dyspnea, which could be more pronounced. The clinical significance is considered moderate, requiring attention but not necessarily contraindication of concurrent use.

Management and Precautions

When ticagrelor and diltiazem are used together, close monitoring for signs of bleeding is essential. Healthcare providers should assess bleeding risk factors, monitor platelet function if available, and educate patients about bleeding precautions. Consider more frequent follow-up visits and laboratory monitoring. If significant bleeding occurs, temporary discontinuation of ticagrelor may be necessary. Alternative calcium channel blockers with less CYP3A4 inhibition potential, such as amlodipine, may be considered if clinically appropriate. Always consult current prescribing information and consider individual patient factors when managing this interaction.

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.

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.