Comparing the safety and efficacy of voriconazole versus posaconazole in the prevention of invasive fungal infections in high-risk patients with hematological malignancies

Hachem, Ray; Assaf, Andrew; Numan, Yazan; Shah, Pankil; Jiang, Ying; Chaftari, Anne-Marie; Raad, Issam

doi:10.1016/j.ijantimicag.2017.03.021

Cited by 36 publications

(38 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Neutropenic patients with acute myeloid leukemia (AML) have among the highest risk for fungal infections when compared to other hematologic malignancies . The proven or probable fungal infection rate in immunocompromised patients with AML ranges from 8–12%, although incidences over 20% have been observed . For those who develop an invasive fungal infection, mortality rates are 30–80% dependent on the specific fungal species .…”

mentioning

confidence: 99%

“…For those who develop an invasive fungal infection, mortality rates are 30–80% dependent on the specific fungal species . Epidemiology studies have demonstrated that mold infections (e.g., Aspergillus species) are more prevalent in neutropenic hematologic malignancy populations . Prophylactic use of antifungals with a broader spectrum of activity, such as voriconazole, reduce the incidence of invasive fungal disease, although breakthrough infections are commonly observed …”

mentioning

confidence: 99%

“…Voriconazole is an effective antifungal prophylactic and is recommended as primary treatment for invasive aspergillosis in immunocompromised patients . Voriconazole displays highly variable nonlinear pharmacokinetics, and there is a strong correlation between voriconazole plasma trough concentrations and clinical outcomes in those with invasive fungal infections .…”

mentioning

confidence: 99%

“…2,3 Epidemiology studies have demonstrated that mold infections (e.g., Aspergillus species) are more prevalent in neutropenic hematologic malignancy populations. 1,2 Prophylactic use of antifungals with a broader spectrum of activity, such as voriconazole, reduce the incidence of invasive fungal disease, although breakthrough infections are commonly observed. [3][4][5][6][7][8] Voriconazole is an effective antifungal prophylactic and is recommended as primary treatment for invasive aspergillosis in immunocompromised patients.…”

mentioning

confidence: 99%

“…[3][4][5][6][7][8] Voriconazole is an effective antifungal prophylactic and is recommended as primary treatment for invasive aspergillosis in immunocompromised patients. 2,5,9,10 Voriconazole displays highly variable nonlinear pharmacokinetics, and there is a strong correlation between voriconazole plasma trough concentrations and clinical outcomes in those with invasive fungal infections. 10,11 Trough concentrations < 1-2 μg/mL are predictive of treatment failure, whereas concentrations > 5-6 μg/ mL are associated with reversible neurotoxicity.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Prospective CYP2C19‐Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations

Hicks

Quilitz

Komrokji

et al. 2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

A risk mitigation strategy was implemented to determine if a higher prophylactic voriconazole dosage in patients with CYP2C19 rapid metabolizer neutropenic acute myeloid leukemia (AML) reduces the incidence of subtherapeutic trough concentrations. Patients with AML (n = 263) were preemptively genotyped for CYP2C19*2, *3, and *17 alleles as part of a single‐center prospective, interventional, quality improvement study. CYP2C19 rapid metabolizers (CYP2C19*1/*17) were recommended to receive interventional voriconazole 300 mg twice daily, ultrarapid metabolizers (CYP2C19*17/*17) were recommended to avoid voriconazole, and all others received the standard prophylactic dosage of 200 mg twice daily. In this real‐world setting, 202 patients (76.8%) were prescribed prophylactic voriconazole, and of these patients 176 (87.1%) received CYP2C19‐guided prophylactic dosing. Voriconazole trough concentrations were obtained for 41 of the 58 (70.7%) CYP2C19 rapid metabolizers prescribed prophylactic voriconazole. Interventional voriconazole resulted in higher plasma trough concentrations (median 2.7 μg/mL) compared with the standard prophylactic dosage (median 0.6 μg/mL; P = 0.001). Subtherapeutic concentrations were avoided in 83.8% of CYP2C19 rapid metabolizers receiving interventional dosage compared to 46.2% receiving standard dosage (P = 0.02). CYP2C19 genotyping to preemptively guide prophylactic voriconazole dosing is feasible and may be a potential strategy for reducing the risk of subtherapeutic trough concentrations that potentiate breakthrough fungal infections.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Prospective CYP2C19‐Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations

Hicks

Quilitz

Komrokji

et al. 2019

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

show abstract

Management of patients with acute myeloid leukemia undergoing therapy with midostaurin: a focus on antifungal prophylaxis

Cairoli

Ferrara

Girmenia

et al. 2020

Hematological Oncology

View full text Add to dashboard Cite

Both therapy and prophylaxis for infectious complications during the treatment of acute myeloid leukemia (AML) have improved, although invasive fungal disease still remains a life‐threatening occurrence. Accordingly, prophylactic strategies with effective and well‐tolerated antifungals remain a cornerstone of management. Herein, the recent literature on antifungal prophylaxis used during the treatment of AML is reviewed, with a focus on the use in combination with midostaurin. The multikinase inhibitor midostaurin targets FMS‐like tyrosine kinase 3 (FLT3) and is approved, in association with 7 + 3, for the treatment of adult patients with newly diagnosed FLT3‐mutated AML. Midostaurin has been shown to extend both overall and event‐free survival in AML patients with an FLT3 mutation and is now the standard of care in FLT3+ AML. Antifungal prophylaxis should be adopted during all phases of treatment in all AML patients, and the strong CYP3A4 inhibitor posaconazole is frequently the preferred agent. As midostaurin is metabolized primarily by CYP3A4, there is a potential for drug–drug interactions that requires further evaluation. At present, the available data suggest that there are no absolute contraindications for coadministration of midostaurin with posaconazole, albeit with cautious monitoring. Considering the survival advantage offered by midostarin, concomitant administration of strong CYP3A4 inhibitors should not be ruled out, although such use should be evaluated cautiously and used on a case‐by‐case basis only if there are no suitable alternatives. It should also be kept in mind that patients with invasive fungal infection undergoing therapy for AML with midostaurin may need prolonged antifungal therapy, which must be based on the administration of the appropriate antifungal agent.

show abstract

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

et al. 2017

View full text Add to dashboard Cite

Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. Since the last edition of antifungal prophylaxis recommendations of the German Society for Haematology and Medical Oncology in 2014, seven clinical trials regarding antifungal prophylaxis in patients with haematological malignancies have been published, comprising 1227 patients. This update assesses the impact of this additional evidence and effective revisions. Our key recommendations are the following: prophylaxis should be performed with posaconazole delayed release tablets during remission induction chemotherapy for AML and MDS (AI). Posaconazole iv can be used when the oral route is contraindicated or not feasible. Intravenous liposomal amphotericin B did not significantly decrease IFI rates in acute lymphoblastic leukaemia (ALL) patients during induction chemotherapy, and there is poor evidence to recommend it for prophylaxis in these patients (CI). Despite substantial risk of IFI, we cannot provide a stronger recommendation for these patients. There is poor evidence regarding voriconazole prophylaxis in patients with neutropenia (CII). Therapeutic drug monitoring TDM should be performed within 2 to 5 days of initiating voriconazole prophylaxis and should be repeated in case of suspicious adverse events or of dose changes of interacting drugs (BIItu). General TDM during posaconazole prophylaxis is not recommended (CIItu), but may be helpful in cases of clinical failure such as breakthrough IFI for verification of compliance or absorption.Electronic supplementary materialThe online version of this article (10.1007/s00277-017-3196-2) contains supplementary material, which is available to authorized users.

show abstract

Comparing the safety and efficacy of voriconazole versus posaconazole in the prevention of invasive fungal infections in high-risk patients with hematological malignancies

Cited by 36 publications

References 17 publications

Prospective CYP2C19‐Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations

Prospective CYP2C19‐Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations

Management of patients with acute myeloid leukemia undergoing therapy with midostaurin: a focus on antifungal prophylaxis

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

Contact Info

Product

Resources

About