Evaluation of Therapeutic Target Attainment With Various Posaconazole Formulations

Background: Therapeutic drug monitoring (TDM) is recommended for posaconazole oral immediate release suspension due to saturable absorption and variable bioavailability; however, it has been suggested that TDM may not be necessary for the delayed-release tablet or intravenous formulations. Our study evaluated target trough attainment with the delayed-release tablet and intravenous solution. Methods: This retrospective, single-center study included adult patients who received posaconazole at a dose of 300 mg every 24 h with at least one steady-state (SS) trough while on the delayed-release tablet or intravenous solution exclusively. Outcomes included the percentage of patients who achieved an initial SS trough ≥ 1300, ≥ 1000, or ≥ 700 ng/mL, in addition to a risk factor analysis. Results: Among the 142 patients included, 74 (52.1%), 102 (71.8%), and 122 (86%) patients had an initial SS trough ≥ 1300, ≥ 1000, and ≥ 700 ng/mL, respectively. More patients achieved an initial SS trough ≥ 1300 ng/mL under the following conditions: total body weight < 90 kg, body mass index < 30 kg/m², or no receipt of acid suppressive therapy. No significant differences were found for median initial SS troughs or percentage of patients with an initial SS trough ≥ 1000 or ≥ 700 ng/mL. Conclusion: With 47.9% of initial SS troughs < 1300 ng/mL and 28.8% < 1000 ng/mL, we recommend TDM for all patients receiving posaconazole for treatment, irrespective of formulation. Initial doses higher than 300 mg q24h should be considered for all patients and strongly considered for patients with risk factors for subtherapeutic troughs.