Amiodarone × Apixaban

Amiodarone and its metabolite inhibit the CYP3A4 enzyme and the P-glycoprotein transporter (amiodarone SmPC), and apixaban is cleared through both routes. Apixaban blood levels may rise, and with them the bleeding risk. There are no direct pharmacokinetic data for this pair (practical guide of the European Heart Rhythm Association, EHRA 2021). The apixaban SmPC of the European Medicines Agency (EMA) lists amiodarone among inhibitors expected to raise apixaban levels to a lesser degree than strong inhibitors. Because amiodarone is cleared slowly, interactions can persist for several months after it is stopped (amiodarone SmPC).

Gum bleeding, nosebleeds, bruising without trauma, blood in the urine or stool, heavy periods. Severe cases include gastrointestinal or intracranial bleeding. Risk is higher in older patients, with body weight 60 kg or less and with impaired kidney function (apixaban SmPC of the European Medicines Agency, EMA).

The combination is allowed with caution. Do not change the apixaban dose because of amiodarone: the apixaban SmPC of the European Medicines Agency (EMA) requires no dose adjustment with inhibitors that are not strong and names amiodarone among them (apixaban SmPC, EMA). In atrial fibrillation, reduce apixaban to 2.5 mg twice daily only by its own criteria: two of three (age 80 years or older, body weight 60 kg or less, serum creatinine 133 µmol/L or higher) or creatinine clearance 15–29 mL/min (apixaban SmPC, EMA). The European Heart Rhythm Association (EHRA) advises caution, especially with polypharmacy. If at least one more risk factor is present (age 75 years or older, body weight 60 kg or less, chronic kidney disease, antiplatelet drugs, non-steroidal anti-inflammatory drugs, systemic steroids, previous bleeding, anaemia or low platelets, frailty or falls), EHRA suggests considering an anticoagulant with fewer interactions or replacing the other drug (EHRA 2021). The effect of amiodarone on other drugs lasts for several months after it is stopped, so caution is needed during that period too (amiodarone SmPC).