Evaluation of Posaconazole Therapeutic Drug Monitoring for Antifungal Prophylaxis in Hematology Patients at a Tertiary Referral Center

This is the authors' abstract. We don't add key points for this paper.

BACKGROUND: Posaconazole (PCZ) is used to prevent invasive fungal infection (IFI) in patients with hematological malignancies or postallogeneic hemopoietic stem cell transplantation (allo-HSCT). However, data are lacking on the utility of PCZ therapeutic drug monitoring (TDM) in this cohort. METHODS: In this retrospective, single-center cohort study, the authors identified patients with hematological malignancies or post-allo-HSCT who were prescribed prophylactic PCZ and had TDM results available from 2015 to 2020 at Alfred Health, Australia. The primary objective was to identify risk factors associated with subtherapeutic target levels (<0.7 mg/L). RESULTS: The authors analyzed 230 PCZ courses (142 patients, 1056 measurements). Of these, 18% of measurements were subtherapeutic and 46.5% of courses were associated with at least 1 subtherapeutic level. Most subtherapeutic levels (51.1%) occurred within the first 14 days after initiation. On multivariate regression, for every 0.1 mg/L increase in D7 PCZ level, there is a 77% reduced risk of having a future subtherapeutic level (Odds Ratio 0.23, 95% CI, 0.12-0.43, P < 0.001). Patients with courses with subtherapeutic levels took longer to attain target threshold (11.5 vs 8.0 days, P 0.01). A guideline-directed, TDM-guided dose-escalation strategy, led by pharmacists, aided in improving target attainment, with 73.4% of courses requiring only 1 dose increase to achieve targets. Adverse events were infrequent (10.9% of courses, 25/230), with hepatotoxicity (9.1%, 21/230) being most prevalent. Breakthrough infection was rare (5.7%). CONCLUSIONS: PCZ levels remain below target for nearly one-half of PCZ courses. Regular TDM during the first 14 days is critical, and patients with subtherapeutic levels at D7 should be prioritized for further close monitoring. A stepwise approach to pharmacist-led TDM-guided dose changes that follows a dosing guideline can improve target attainment for PCZ.