Original Research
Saturday, October 12, 2024
11:30 AM–01:00 PM
Abstract
Introduction: Itraconazole and posaconazole are frequently prescribed following transplantation to prevent and treat fungal infections. Navigating drug interactions is challenging due to these agents’ potent CYP3A4 inhibition and literature describing concurrent apixaban, a CYP3A4 substrate, is limited.
Research Question or Hypothesis: We hypothesized that routine apixaban dose reduction with itraconazole or posaconazole would be associated with goal apixaban levels.
Study Design: Single-center, retrospective, case series of adult cardiothoracic transplant recipients taking itraconazole or posaconazole with apixaban 2.5 mg twice daily (BID) for atrial fibrillation or venous thromboembolism (VTE).
Methods: Institution practice reduces apixaban to 2.5 mg BID with itraconazole or posaconazole and obtains apixaban calibrated anti-Xa assay within five days with goal trough 50-150 ng/mL. Antifungal and apixaban levels were drawn within seven days. The primary outcome was the impact of itraconazole and posaconazole on apixaban exposure. Clinical outcomes of major bleed per ISTH criteria, VTE, stroke, and clot resolution are described. Apixaban levels and clinical outcomes were compared using Wilcoxon rank sum and Fisher’s exact tests.
Results: Twenty-six transplant recipients were identified: 18 (69%) lung, 2 (8%) heart, 6 (23%) multi-organ. Seventeen levels from 14 patients on itraconazole displayed median [IQR] apixaban trough 143 ng/mL [95-183], 59% within and 41% above goal. Fourteen levels from 12 patients on posaconazole displayed median [IQR] apixaban trough 124 ng/mL [93.8-156.8], 71% within and 29% above goal. Linear regression performed suggests any itraconazole or posaconazole exposure potentiates increased apixaban exposure. Two major bleed events, two VTE, two stroke, and eight clot resolution were identified.
Conclusion: Apixaban 2.5 mg BID with itraconazole or posaconazole generally results in goal apixaban exposure but with notable variability. Empiric apixaban dose reduction is likely appropriate with any itraconazole or posaconazole exposure as data could not demonstrate a proportional increase in apixaban exposure with increasing azole concentrations. Apixaban TDM is highly encouraged for individualized dosing with itraconazole or posaconazole.
Presenting Author
Kennedy Concannon PharmDMayo Clinic Hospital
Authors
Kristin Cole MS
Mayo Clinic
Rachel Huntsman PharmD
Mayo Clinic Hospital
Cassie Kennedy MD
Mayo Clinic Hospital
Adley Lemke PharmD
Mayo Clinic Hospital
Andrew Rosenbaum MD
Mayo Clinic Hospital