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. 2024 Apr;40(2):204-212.
doi: 10.1007/s12288-023-01709-3. Epub 2023 Oct 29.

A Prospective Study to Evaluate the Effect of Therapeutic Drug Monitoring-Based Posaconazole Prophylaxis on Invasive Fungal Infection Rate During Acute Myeloid Leukemia Induction Therapy

Mounika Boppana  1   2 , Manju Sengar  3   4 , Hasmukh Jain  3 , Murari Gurjar  5 , Madhavi Ambotkar  5 , Vikram Gota  5 , Avinash Bonda  6 , Bhausaheb Bagal  3 , Jayashree Thorat  3 , Anant Gokarn  7 , Lingaraj Nayak  3 , Nitin Shetty  8 , Akshay Baheti  8 , Smruti Mokal  9 , Sadhana Kannan  9 , Alok Shetty  1 , Thomas Eipe  1
Affiliations

A Prospective Study to Evaluate the Effect of Therapeutic Drug Monitoring-Based Posaconazole Prophylaxis on Invasive Fungal Infection Rate During Acute Myeloid Leukemia Induction Therapy

Mounika Boppana et al. Indian J Hematol Blood Transfus. 2024 Apr.

Abstract

Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality in de-novo acute myeloid leukemia patients receiving induction chemotherapy. Despite using posaconazole, a broad-spectrum antifungal, for IFI prophylaxis, the breakthrough IFI rate is high in the real-world setting. One of the reasons could be frequent suboptimal plasma posaconazole levels. In the present study, we evaluated if therapeutic drug monitoring (TDM) guided posaconazole prophylaxis can reduce the IFI rates in comparison to a historical cohort. We enrolled 90 patients, > / = 16 years of age, without baseline IFIs, planned for remission induction therapy. All patients were started on posaconazole suspension 200 mg TDS and the dose was increased in a stepwise manner if trough levels were found to be suboptimal (< 350 ng/ml for day 2 or < 700 ng/ml subsequently). The TDM based approach resulted in a significant decline in breakthrough IFI rates (18% versus 52%, P < 0.0001) A total of 69 patients (78%) required dose escalation. Thirty-one patients required change in antifungals due to either suboptimal levels, persistent fever, diarrhoea or vomiting. We could not demonstrate an exposure-response relationship but the difference in IFI rates in patients with a median posaconazole level > / = 700 ng/ml (0%) and < 700 ng/ml (21.6%) was clinically meaningful. Posaconazole levels were found to be significantly lower in patients on antacids and prokinetics. The incidence of posaconazole-related grade 3 toxicity was low (2.3%). Thus TDM-based dosing of posaconazole helps reduce breakthrough IFI rate and should be a part of posaconazole prophylaxis.

Supplementary information: The online version contains supplementary material available at 10.1007/s12288-023-01709-3.

Keywords: AML induction; Acute myeloid leukemia (AML); Invasive fungal infections (IFIs); Posaconazole; Therapeutic drug monitoring (TDM).

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Conflict of interest statement

Conflict of interestThe authors have declared no conflicts of interest.Ethical ApprovalAll authors declare that they approve the final version of the manuscript. In addition, the authors have declared no conflicts of interest. The study was approved by the institutional ethics committee and was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. The study was registered in the Clinical Trials Registry – India (CTRI) (CTRI/2017/06/008810).

Figures

Fig. 1
Fig. 1
Serum posaconazole trough concentrations and dose escalation. Legend—A scatter plot showing the three posaconazole dosing levels versus the serum trough concentration (ng/ml) of all the 88 patients at various time points after starting posaconazole
See this image and copyright information in PMC

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