Bleeding Risk with Apixaban and Systemic Fluconazole Use

Bleeding Risk with Apixaban and Systemic Fluconazole Use Posted By:

We, as healthcare professionals, are aware that we must check for drug interactions in our patients taking multiple medications. In the specific setting of atrial fibrillation (AF), patients usually have comorbidities and take multiple medications in addition to anticoagulants such as warfarin or apixaban, a direct oral anticoagulant (DOAC). Direct oral anticoagulants act by direct inhibition of thrombin or coagulation factor Xa; they typically have a low risk of drug-drug interactions.

However, in a recent retrospective , case-crossover study, it was discovered that systemic fluconazole use was associated with a 3.5-fold increased bleeding risk in patients with AF receiving apixaban vs apixaban only (both explored over 30-day exposure windows). It was noted that GI bleed accounted for the majority (65%) of bleeding incidents experienced after both apixaban and fluconazole use. This increased risk was only seen with systemic fluconazole + apixaban. The study reports that the increased bleeding risk did not occur with topical fluconazole + apixaban or systemic fluconazole + rivaroxaban or dabigatran.

While advantages of DOACs include their typically lower risk of drug-drug interactions—in addition to rapid onset and offset of action, a wide therapeutic window, and a predictable anticoagulant response that allows for fixed doses and eliminates the need for frequent monitoring—this study highlights the importance of investigating potential drug-drug interactions despite the "lower" risk. We must all be vigilant about the possibility of medication interactions, even with agents that might not typically be considered for this, and consider options for modifying therapies to reduce risks while optimizing therapeutic outcomes. Drug-drug interactions have the potential to propagate serious outcomes for our patients, and we must be alert to them.