What is the interaction between Apixaban (Direct Oral Anticoagulant) and Amiodarone (Antiarrhythmic medication)?

From the Guidelines

Apixaban and amiodarone should be used together with caution due to a potential drug interaction that may increase apixaban levels in the blood, thereby raising the risk of bleeding complications. According to a study published in Circulation: Arrhythmia and Electrophysiology 1, apixaban interacts with drugs that induce or inhibit CYP3A4 or P-gp, and strong CYP3A4 inhibitors, such as amiodarone, can increase the maximum concentration (Cmax) and area under the curve (AUC∞) of apixaban, leading to an increased risk of bleeding.

Some key points to consider when using apixaban and amiodarone together include:

• Avoiding the combination of apixaban with strong CYP3A4 and P-gp inhibitors, such as amiodarone, if possible 1
• Reducing the dose of apixaban by 50% if the combination is unavoidable and the patient is on a regimen of 5-10 mg twice daily 1
• Close monitoring for signs of bleeding, including unusual bruising, nosebleeds, blood in urine or stool, and excessive menstrual bleeding
• Educating patients about bleeding risks and advising them to inform all healthcare providers about this combination therapy before any procedures
• Considering the use of andexanet alfa to reverse apixaban's anticoagulant effects in emergency situations if bleeding occurs.

It is essential to weigh the benefits and risks of using apixaban and amiodarone together and to closely monitor patients for signs of bleeding complications. Regular INR monitoring is not useful since apixaban doesn't affect INR values predictably. Experts recommend avoiding the combination of apixaban with strong CYP3A4 and P-gp inhibitors, such as amiodarone, if possible 1.

From the Research

Apixaban and Amiodarone Drug Interaction

• The interaction between apixaban and amiodarone has been studied in several research papers 2, 3, 4, 5, 6.
• A nationwide cohort study found that the rates of major bleeding were similar in patients treated with apixaban and warfarin in combination with amiodarone 2.
• Another study found that coadministration of amiodarone and apixaban resulted in a trend toward increased apixaban concentrations, but the extent of elevation suggests that empiric dose changes are not necessary 3.
• A population-based, nested case-control study found that current use of amiodarone was associated with a significant increase in major bleeding risk in patients with atrial fibrillation on a direct oral anticoagulant (DOAC) 4.
• A retrospective cohort study found that patients with atrial fibrillation treated with amiodarone during apixaban or rivaroxaban use had a greater risk for bleeding-related hospitalizations than those treated with flecainide or sotalol 5.
• A case report suggested that a drug-drug interaction between apixaban and amiodarone may have contributed to the development of hemopericardium in an 80-year-old man with paroxysmal atrial fibrillation 6.

Bleeding Risk

• The risk of bleeding-related hospitalizations was increased in patients treated with amiodarone and apixaban or rivaroxaban compared to those treated with flecainide or sotalol 5.
• The incidence of major bleeding was similar in patients treated with apixaban and warfarin in combination with amiodarone 2.
• Current use of amiodarone was associated with a significant increase in major bleeding risk in patients with atrial fibrillation on a DOAC 4.

Apixaban Concentrations

• Coadministration of amiodarone and apixaban resulted in a trend toward increased apixaban concentrations 3.
• The extent of elevation suggests that empiric dose changes are not necessary, but individual patients may benefit from monitoring and dose adjustment 3.