Key result
Reduced-dose apixaban with azole antifungals achieves on-target trough concentrations across ~100% of expected ranges.
Why the study?
Itraconazole and posaconazole are potent CYP3A4 inhibitors frequently prescribed after transplantation, and literature describing their concurrent use with apixaban, a CYP3A4 substrate, is limited.
Does routine dose reduction of apixaban to 2.5 mg twice daily maintain target pharmacokinetic exposure and acceptable clinical outcomes when administered concurrently with itraconazole or posaconazole in cardiothoracic transplant recipients?
Observational (n=28)
No
Does routine dose reduction of apixaban to 2.5 mg twice daily maintain target pharmacokinetic exposure and acceptable clinical outcomes when administered concurrently with itraconazole or posaconazole in cardiothoracic transplant recipients?
In cardiothoracic transplant recipients taking concurrent itraconazole or posaconazole, reducing apixaban to 2.5 mg twice daily achieves drug exposure comparable to standard dosing in the general population, though therapeutic drug monitoring is encouraged for individualized dosing.
Answers are grounded in this paper and cite their sources.
Reduced-dose apixaban with itraconazole or posaconazole achieved expected exposure; leaves open optimal strategy and safety without prospective trials.
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. This retrospective study of cardiothoracic transplant recipients evaluates the impact of itraconazole and posaconazole on apixaban exposure and reports clinical outcomes from routine apixaban dose reduction. Institutional practice reduces apixaban to 2.5 mg twice daily with itraconazole or posaconazole and obtains apixaban therapeutic drug monitoring (TDM), expected range 34-230 ng/mL. Eighteen levels collected in 15 patients on itraconazole displayed a median [IQR] apixaban trough of 143 ng/mL [95-195]. Fifteen levels collected in 13 patients on posaconazole displayed a median [IQR] apixaban trough of 124 ng/mL [93-174]. Two major bleed events, three VTE, two stroke, and eight instances of clot resolution were identified. Reduced-dose apixaban resulted in apixaban exposure similar to normal dosing in the general population. Apixaban TDM is encouraged for individualized dosing when administered with itraconazole and posaconazole.
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Concannon et al. (2025) conducted an observational in Cardiothoracic transplant recipients on concurrent apixaban and itraconazole or posaconazole (n=28). Concurrent reduced-dose apixaban (2.5 mg twice daily) with itraconazole or posaconazole vs. Expected apixaban therapeutic range (34-230 ng/mL) was evaluated on Apixaban trough concentrations (ng/mL) and clinical events (major bleed, VTE, stroke, clot resolution). Reduced-dose apixaban (2.5 mg BID) with itraconazole or posaconazole yielded median troughs of 143 ng/mL [IQR 95-195] and 124 ng/mL [IQR 93-174], within the expected 34-230 ng/mL range.
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