Summary

St John's Wort significantly reduces apixaban blood levels by inducing CYP3A4 and P-glycoprotein, potentially decreasing anticoagulant effectiveness. This interaction may increase the risk of thrombotic events in patients taking apixaban for stroke prevention or blood clot treatment.

Introduction

Apixaban (brand name Eliquis) is a direct oral anticoagulant (DOAC) belonging to the factor Xa inhibitor class, commonly prescribed for stroke prevention in atrial fibrillation and treatment of venous thromboembolism. St John's Wort (Hypericum perforatum) is a popular herbal supplement used for mild to moderate depression and mood disorders. While many patients view herbal supplements as safe, St John's Wort is a potent inducer of drug-metabolizing enzymes and can significantly affect prescription medications.

Mechanism of Interaction

St John's Wort contains hyperforin and other compounds that strongly induce cytochrome P450 3A4 (CYP3A4) enzymes and P-glycoprotein (P-gp) efflux pumps. Apixaban is metabolized primarily by CYP3A4 and is also a substrate for P-glycoprotein. When St John's Wort induces these pathways, it accelerates apixaban metabolism and increases its efflux from cells, resulting in significantly reduced plasma concentrations of apixaban. Studies have shown that St John's Wort can decrease apixaban exposure by approximately 54%, substantially compromising its anticoagulant effect.

Risks and Symptoms

The primary clinical risk of this interaction is reduced anticoagulant effectiveness, which may lead to treatment failure and increased risk of thrombotic events including stroke, pulmonary embolism, or deep vein thrombosis. Patients taking apixaban for atrial fibrillation may face increased stroke risk, while those being treated for existing blood clots may experience clot progression or recurrence. The interaction effect can persist for 1-2 weeks after discontinuing St John's Wort due to the time required for enzyme activity to return to baseline levels.

Management and Precautions

Patients taking apixaban should avoid St John's Wort supplementation. If a patient is already taking both, St John's Wort should be discontinued with close monitoring for signs of thrombotic events. Healthcare providers should counsel patients about the risks and consider alternative treatments for depression or mood disorders that do not interact with anticoagulants. Regular monitoring of anticoagulant effectiveness through clinical assessment is recommended, though routine coagulation testing is not typically required for apixaban. Patients should be educated to inform all healthcare providers about herbal supplement use and to avoid starting new supplements without medical consultation.

Apixaban interactions with food and lifestyle

Apixaban does not have any clinically significant food interactions and can be taken with or without food. However, patients should limit alcohol consumption while taking apixaban, as excessive alcohol use may increase the risk of bleeding. Additionally, patients should avoid activities with high risk of injury or trauma that could lead to bleeding, and should inform healthcare providers before any surgical or dental procedures. Grapefruit juice does not significantly affect apixaban levels, unlike some other medications.

St John's Wort interactions with food and lifestyle

St John's Wort should be taken consistently with regard to food - either always with food or always on an empty stomach - to maintain consistent absorption. Avoid excessive sun exposure and use sun protection, as St John's Wort can increase photosensitivity and risk of sunburn. Limit alcohol consumption as it may increase the risk of side effects and reduce the effectiveness of St John's Wort. Maintain consistent timing of doses to optimize therapeutic effects.