From the Guidelines
Diltiazem can significantly increase the risk of bleeding when used with direct oral anticoagulants (DOACs) due to its inhibition of P-glycoprotein and CYP3A4 enzymes, and therefore, careful dose adjustment and monitoring are crucial when combining these medications. The interaction between diltiazem and DOACs, such as apixaban, rivaroxaran, edoxaban, and dabigatran, can lead to increased plasma concentrations of the anticoagulants, thereby enhancing their anticoagulant effects and the risk of bleeding 1.
When using diltiazem with DOACs, it is essential to consider the potential for drug interactions and to adjust the doses of the DOACs accordingly. For instance, with apixaban, a dose reduction of 50% may be necessary when used concomitantly with diltiazem, while for rivaroxaran and edoxaban, caution and close monitoring for signs of bleeding are recommended 1. Dabigatran may require a dose reduction to 110 mg twice daily when combined with diltiazem.
Regular monitoring for signs of bleeding, such as unusual bruising, nosebleeds, or blood in urine or stool, is vital when patients are on this combination therapy 1. Patients should be informed about the potential risks and benefits of this combination and should carry medical alert information. Any adjustments to the doses of these medications should be made under close medical supervision to ensure appropriate anticoagulation while minimizing the risk of bleeding.
The mechanism behind this interaction involves diltiazem's inhibition of the transport and metabolic pathways that eliminate DOACs from the body, leading to higher plasma concentrations and prolonged anticoagulant effects. Given the potential for significant bleeding risk, careful consideration and management of this interaction are necessary to prioritize patient safety and outcomes.
From the Research
Interaction between Diltiazem and DOACs
- The concomitant use of diltiazem with direct oral anticoagulants (DOACs) may increase the risk of bleeding in patients with atrial fibrillation 2, 3.
- Studies have shown that the use of diltiazem with DOACs such as rivaroxaban, apixaban, and dabigatran may potentiate the bleeding risk through pharmacokinetic interactions 2.
- The risk of bleeding with diltiazem and DOACs was observed in both patients with and without chronic kidney disease (CKD) 2.
- A study found that current use of diltiazem was associated with an increased risk of major bleeding in patients with atrial fibrillation receiving a DOAC, with an adjusted odds ratio of 1.37 (95% CI, 1.08-1.73) 3.
- Another study found that the use of dabigatran with verapamil or diltiazem was associated with a higher bleeding rate compared to the use of amlodipine or metoprolol, with a hazard ratio of 1.52 (95% CI, 1.05-2.20) 4.
Bleeding Risk with Diltiazem and DOACs
- The overall bleeding rate was higher in patients receiving dabigatran with verapamil or diltiazem compared to those receiving amlodipine or metoprolol, with a hazard ratio of 1.52 (95% CI, 1.05-2.20) 4.
- The risk of gastrointestinal bleeding was also higher in patients receiving dabigatran with verapamil or diltiazem, with a hazard ratio of 2.16 (95% CI, 1.30-3.60) 4.
- A study found that the use of diltiazem with DOACs was associated with an increased risk of any bleeding-related hospitalization, with an adjusted hazard ratio of 1.56 (95% CI, 1.15-2.12) 2.
Clinical Implications
- Clinicians should be aware of the potential increased risk of bleeding when prescribing diltiazem with DOACs, particularly in patients with atrial fibrillation 2, 3.
- The benefits and risks of concomitant use of diltiazem and DOACs should be carefully considered, and patients should be closely monitored for signs of bleeding 2.