Use of antifungal drugs in hematology

Nucci, Márcio

doi:10.5581/1516-8484.20120095

Cited by 9 publications

(9 citation statements)

References 69 publications

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“…Drug-drug interactions (DDI) with CYP3A-mediated metabolism are particularly problematic in patients with B-cell malignancies such as CLL/SLL because these patients are at risk for systemic fungal infections due to underlying disease-related immune dysfunction and therapy-related immunosuppression [22]. Prophylactic or therapeutic use of azole anti-fungals is common in CLL/SLL [23], and the agents in this therapeutic class (e.g., voriconazole, posaconazole) are moderate-to-strong inhibitors of CYP3A [24,25]. Because of the potential concomitant usage of these agents with zanubrutinib, it is important to understand the DDI potential between zanubrutinib and CYP3A inhibitors and inducers.…”

Section: Introductionmentioning

confidence: 99%

Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects

Mu¹,

Tang²,

Novotny³

et al. 2019

Cancer Chemother Pharmacol

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Purpose Zanubrutinib (BGB-3111) is a potent Bruton's tyrosine kinase inhibitor with promising clinical activity in B-cell malignancies. Zanubrutinib was shown to be mainly metabolized through cytochrome P450 3A (CYP3A) in vitro. We evaluated the effect of steady-state rifampin (a strong CYP3A inducer) and steady-state itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics (PK), safety, and tolerability of zanubrutinib in healthy Asian and non-Asian subjects.Methods In this open-label, two-part clinical study, 20 participants received a single oral dose of zanubrutinib (320 mg) and oral rifampin (600 mg) in Part A, and 18 participants received a single oral dose of zanubrutinib (20 mg) and oral itraconazole (200 mg) in Part B. Serial blood samples were collected after administration of zanubrutinib alone and zanubrutinib in combination with rifampin or itraconazole for the measurement of PK parameters. Results Coadministration with rifampin decreased AUC 0-∞ of zanubrutinib by 13.5-fold and C max by 12.6-fold. Coadministration with itraconazole increased the AUC 0-∞ of zanubrutinib by 3.8-fold and C max by 2.6-fold. The PK of zanubrutinib was consistent between Asian and non-Asian subjects, and zanubrutinib was well tolerated in this study. Conclusions These results confirm that zanubrutinib is primarily metabolized by CYP3A in humans. The PK of zanubrutinib was comparable between Asian and non-Asian subjects and, therefore, no dose modifications are necessary for zanubrutinib in these ethnic populations.

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Section: Introductionmentioning

confidence: 99%

Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects

Mu¹,

Tang²,

Novotny³

et al. 2019

Cancer Chemother Pharmacol

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“…Although the initiation of appropriate antifungal therapy is crucial and associated with improved outcomes, the management of antifungal treatment in this heterogeneous population is a matter of great research [3,6,11,12,13,14]. …”

Section: Discussionmentioning

confidence: 99%

“…Host factors are important for predicting IFIs as well, as they are the determinants of the outcome [6]. Neutropenia, one of the host factors, is still a significant risk factor, and resolution of neutropenia has a key role in complete recovery from an IFI [6,19]. The duration and also the severity of neutropenia are critical, but there was no practical tool that combined both the duration and the severity of neutropenia in its evaluation approach.…”

Section: Discussionmentioning

confidence: 99%

“…Although there has been significant progress in the management of febrile neutropenic cancer patients related to increasing protective measures and antifungal agents, neutropenia is still a critical risk factor for IFI. Profound (<100 neutrophils/µL) and prolonged (>10 days) neutropenia is associated with a higher risk of invasive aspergillosis [1,2,3,4,5,6,7]. …”

Section: Introductionmentioning

confidence: 99%

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D-index: A New Scoring System in Febrile Neutropenic Patients for Predicting Invasive Fungal Infections

Yılmaz

Coşkun²,

Elhan³

et al. 2016

Tjh

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Objective:Neutropenia is a critical risk factor for invasive fungal infections (IFIs). We retrospectively performed this study to assess the performance of the D-index, a new test that combines both the duration and the severity of neutropenia, in predicting IFIs among patients with acute myelogenous leukemia.Materials and Methods:Fifteen patients with IFIs and 28 patients who did not develop IFIs were enrolled in the study. The D-index was defined as the area over the neutrophil curve, whereas the cumulative-D-index (c-D-index) was the area over the neutrophil curve from the start of neutropenia until the first clinical manifestation of IFI. Results:The D-index and the c-D-index tended to be significantly higher in patients with IFIs, with medians of 10,150 (range: 4000-22,000) and 5300 (range: 2300-22,200), respectively (p=0.037 and p=0.003, respectively). The receiver operating characteristic analyses showed that there was a cutoff point of 3875 for the D-index in predicting IFI; the sensitivity, specificity, and positive and negative predictive values were 100%, 67.9%, 35.4%, and 100%, respectively. There was also a cutoff point of 4225 for the c-D-index in predicting IFI; the sensitivity, specificity, and positive and negative predictive values for the c-D-index were 93.3%, 71.4%, 36.6%, and 98.4%.Conclusion:The D-index and especially the c-D-index could be useful tools with high negative predictive value to exclude as well as to predict IFIs in the management of neutropenic patients.

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“…Candidemia and IFIs are major complications in patients with HMs who develop prolonged and severe neutropenia. Additionally, IFIs are difficult to diagnose in these severely immunocompromised patients [88][89][90][91]. In patients with MM prior to the introduction of novel therapies, IFIs were encountered in patients treated with traditional intensive cytotoxic chemotherapeutic regimens and mortality rates due to IFIs were reaching 60% [91].…”

Section: Fungal Infections In MMmentioning

confidence: 99%

Infections in Patients with Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

Al-Jasser¹,

Al-Anazi²

2019

Update on Multiple Myeloma

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Multiple myeloma is a common hematologic malignancy that is associated with reduced cellular as well as humoral immunity ultimately causing various infectious complications. The recent advances in the management of myeloma have led not only to prolonged survival but also to shifts in the incidence as well as the spectrum of infections encountered. This book chapter will be an updated review on the infectious complications in patients with multiple myeloma in the era of novel agents, stem cell therapies, and monoclonal antibodies. It will cover causes of immunosuppression, timing, and types as well as management of the various infections reported with various therapeutic modalities that are currently utilized in the management of myeloma patients.

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Use of antifungal drugs in hematology

Cited by 9 publications

References 69 publications

Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects

Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects

D-index: A New Scoring System in Febrile Neutropenic Patients for Predicting Invasive Fungal Infections

Infections in Patients with Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

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