Apixaban × Fluconazole

Fluconazole is a moderate inhibitor of the CYP3A4 enzyme (fluconazole SmPC), and apixaban is partly cleared through this enzyme. The apixaban SmPC of the European Medicines Agency (EMA) lists fluconazole among inhibitors expected to raise apixaban levels to a lesser degree than strong inhibitors. There are no figures for this pair: the European Heart Rhythm Association (EHRA) reports no data yet (EHRA 2021). Fluconazole keeps inhibiting the enzyme for 4–5 days after the last dose (fluconazole SmPC).

Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.

Do not change the apixaban dose during a fluconazole course. The apixaban SmPC of the European Medicines Agency (EMA) requires no dose adjustment with inhibitors that are not strong and names fluconazole among them (apixaban SmPC, EMA). Choose the apixaban dose by its usual rules: in atrial fibrillation, use 2.5 mg twice daily if two of three criteria are present (age 80 years or older, body weight 60 kg or less, serum creatinine 133 µmol/L or higher) or if creatinine clearance is 15–29 mL/min (apixaban SmPC, EMA). Tell the patient about signs of bleeding, and stop apixaban in severe bleeding (apixaban SmPC, EMA).