Journal of Clinical Research

Evaluation of the Implementation of a Voriconazole Pharmacokinetic Monitoring Program in Hematological Patients

Abstract

Paula Torrano Belmonte*

Background: Invasive Fungal Infections (IFI) is a significant cause of morbidity and mortality in patients with hematological malignancies. Voriconazole is widely used for the prophylaxis and treatment of IFIs. However, its efficacy and safety are influenced by factors such as nonlinear pharmacokinetics, genetic polymorphisms, hepatic metabolism, and drug interactions. Pharmacokinetic (PM) monitoring is an essential tool to optimize voriconazole therapy. Objectives: This study aimed to evaluate the impact of the implementation of a voriconazole MF program on drug safety and dosing optimization in hematological patients. Methods: A prospective study was conducted in hospitalized patients with hematological malignancies who received voriconazole between January and December 2023. Inclusion criteria included adults under therapy with both oral and intravenous voriconazole, with at least one plasma level determination. Voriconazole levels were measured using the ARK Voriconazole II Assay, and dose adjustments were made based on predefined therapeutic ranges (1-4 mcg/mL). Statistical analyzes were performed with SPSS v28, applying non-parametric tests. Results: A total of 42 blood samples from 32 patients were analyzed. Most patients (71.42%) received oral voriconazole. Therapeutic levels (1-4 mcg/mL) were reached in 57.14% of the samples, while 28.57% were supratherapeutic and 9.52% were infratherapeutic. Weight was significantly associated with voriconazole levels (p=0.032), while age and route of administration were not. Adverse events were observed in 17 cases, 82% in patients with supratherapeutic levels, including hepatotoxicity, neurotoxicity and renal alterations. The pharmacist's recommendations led to dose modifications in 40.47% of cases, with an acceptance rate of 88.10% by physicians. Conclusions: Implementation of voriconazole MF has proven to be a viable strategy to improve safety. It was observed that 82% of adverse effects occurred in patients with levels greater than 4 mcg/mL, highlighting the value of monitoring as a predictive tool. Furthermore, the intervention of hospital pharmacists had high acceptance (88%), which supports the importance of their role in optimization.