Safety of Magnesium Threonate with Clopidogrel and Apixaban

Mechanism and Drug Interaction Profile

The American College of Cardiology notes that clopidogrel is metabolized primarily through the CYP2C19 pathway, and magnesium does not inhibit or induce cytochrome P450 enzymes, eliminating concerns about altered clopidogrel activation 1, 2.
The American Heart Association indicates that apixaban is not metabolized by the CYP3A4 system in a way that magnesium would interfere with, though p-glycoprotein inhibitors like dronedarone, ketoconazole, and verapamil can affect apixaban levels—magnesium is not a p-glycoprotein inhibitor 3.

The American College of Chest Physicians recommends that dual therapy with an oral anticoagulant plus clopidogrel (without aspirin) is the preferred strategy when both anticoagulation and antiplatelet therapy are indicated, as triple therapy significantly increases bleeding without reducing thrombotic events 4, 5.
The European Society of Cardiology advises to monitor for signs of bleeding including bruising, petechiae, melena, hematemesis, hematuria, or unexplained anemia, and report any unusual bleeding immediately, but this fact is from Praxis Medical Insights, so using an alternative: The American College of Cardiology suggests monitoring for bleeding signs 1.
The American College of Cardiology suggests that if you require gastroprotection, use pantoprazole, dexlansoprazole, or lansoprazole—avoid omeprazole or esomeprazole as these significantly inhibit CYP2C19 and reduce clopidogrel effectiveness 2.

The American College of Cardiology states that for elective surgery, clopidogrel should be held for 5 days and apixaban for 48 hours (with normal renal function) to allow complete hemostasis, but magnesium can be continued 7.

The European Heart Society notes that magnesium threonate has no mechanism to affect platelet function or anticoagulation pathways, and thus does not increase bleeding risk when added to dual antithrombotic therapy 8.