scholarly journals Evaluation of Serum Posaconazole Concentrations in Patients with Hematological Malignancies Receiving Posaconazole Suspension Compared to the Delayed-Release Tablet Formulation

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Morgan Belling ◽  
Abraham S. Kanate ◽  
Alexandra Shillingburg ◽  
Xiaoxiao Lu ◽  
Sijin Wen ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Hematological Malignancies ◽  
Fungal Infections ◽  
Group Versus ◽  
Primary Objective ◽  
Serum Concentrations ◽  
Qtc Prolongation ◽  
Delayed Release ◽  
Release Tablet

Posaconazole (PCZ) is frequently used for prophylaxis against invasive fungal infections (IFI) in patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Posaconazole is commercially available as an oral suspension (PCZ-susp) and as a delayed-release tablet (PCZ-tab). Differences in absorption and bioavailability between these formulations may result in variability in serum posaconazole concentrations. The primary objective of this retrospective analysis was to compare attainment of goal serum posaconazole steady state concentrations (Css) ≥ 700 ng/ml in patients with AML/MDS undergoing induction chemotherapy receiving PCZ-susp 600–800 mg per day (N=118) versus PCZ-Tablet 300 mg twice daily for one day, followed by 300 mg daily (N=64). Sixty-two patients (97%) in the PCZ-tab group compared to 20 patients (17%) in the PCZ-susp group achieved goal Css  (P<0.0001). Median posaconazole serum Css was 1,665 ng/ml (522–3,830 mg/ml) in the PCZ-tab group versus 390 ng/ml (51–1,870 ng/ml) in the PCZ-susp group (P<0.0001). There was no difference in hepatotoxicity, QTc prolongation, or breakthrough IFI. Patients receiving PCZ-tab were significantly more likely to achieve goal Css and demonstrated higher Css versus patients receiving PCZ-susp. Prospective studies are needed to assess the potential correlation of serum concentrations with efficacy and toxicity.

scholarly journals Prevention of Invasive Aspergillus Fungal Infections with the Suspension and Delayed-Release Tablet Formulations of Posaconazole in Patients with Haematologic Malignancies

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Elisabeth Leclerc ◽  
David Combarel ◽  
Madalina Uzunov ◽  
Véronique Leblond ◽  
Christian Funck-Brentano ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Delayed Release ◽  
Tablet Formulations ◽  
Haematologic Malignancies ◽  
Release Tablet

Comparison of serum concentrations between different dosing strategies of posaconazole delayed-release tablet at a large academic medical centre

Mycoses ◽  
2016 ◽  
Vol 60 (4) ◽  
pp. 241-243 ◽  
Author(s):  
Sarah Welch ◽  
Andrea Pallotta ◽  
Catherine Weber ◽  
Caitlin Siebenaller ◽  
Eric Cober ◽  
...  
Keyword(s):  
Medical Centre ◽  
Serum Concentrations ◽  
Academic Medical Centre ◽  
Delayed Release ◽  
Academic Medical ◽  
Dosing Strategies ◽  
Release Tablet

scholarly journals Impact of fluconazole versus posaconazole prophylaxis on the incidence of fungal infections in patients receiving induction chemotherapy for acute myeloid leukemia

2015 ◽  
Vol 38 (3) ◽  
pp. 235 ◽  
Author(s):  
AlexanderTuan Falk ◽  
Hélène Raberin ◽  
Sandrine Menguy ◽  
Denis Guyotat ◽  
Nicolas Magné ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Acute Myeloid

scholarly journals Comparison of Serum Concentrations Between Posaconazole Delayed-Release Tablet and Oral Suspension at a Large Academic Medical Center

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Sarah Welch ◽  
Andrea Pallotta ◽  
Catherine Weber ◽  
Caitlin Siebenaller ◽  
Eric Cober ◽  
...  
Keyword(s):  
Medical Center ◽  
Academic Medical Center ◽  
Oral Suspension ◽  
Serum Concentrations ◽  
Delayed Release ◽  
Academic Medical ◽  
Release Tablet

scholarly journals 594. Micafungin Prophylaxis in Acute Myeloid Leukemia Adult Patients Undergoing Induction Chemotherapy

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S400-S401
Author(s):  
Justine Abella Ross ◽  
Jonathan Yong ◽  
Jason Chen ◽  
Deron Johnson ◽  
Doreen Pon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Clinical Failure ◽  
Newly Diagnosed ◽  
Start Date ◽  
Increased Risk ◽  
Acute Myeloid

Abstract Background Patients (pts) with newly diagnosed acute myeloid leukemia (AML) undergoing induction chemotherapy are at increased risk for invasive fungal infections (IFI). Guidelines recommend posaconazole prophylaxis (ppx), but use is precluded by interactions and adverse effects. Micafungin (MCF) is an alternative, but data is limited by small prospective and retrospective studies. Primary objective: describe incidence of probable/proven IFI until neutrophil recovery (ANC ≥ 500 cells/µL) or 28 days after induction start date, whichever occurred first, in pts receiving MCF ppx. Secondary objective: describe incidence of clinical failure to MCF prophylaxis. Methods Retrospective review (January 2017 to January 2020) of newly diagnosed AML adult pts undergoing 7 + 3 using idarubicin (7 + 3-ida), 7 + 3 using daunorubicin (7 + 3-dau), venetoclax/decitabine (VEN/DEC), or venetoclax/azacitadine (VEN/AZA) receiving MCF ppx for at least 7 days included. Diagnosis of IFI &lt; 30 days prior to induction, liver function tests (LFT) 5x ULN at start of induction, or evidence of refractory disease after induction excluded. Probable/proven IFI defined by EORTC criteria. Clinical failure: changing to a different antifungal class for any reason until ANC recovery or 28 days after induction start date. Results Ninety-five pts included. Baseline characteristics: mean (±SD) age 57.8 (±13.0) years; 53.6% males. 62% (59/95) 7 + 3-ida, 13.7% (13/95) 7 + 3-dau, 15.8% (15/95) VEN/DEC, 8.4% (8/95) VEN/AZA. Mean (±SD): 32.5% (±26) blasts, WBC 13.2 (±23.8), ANC 2.4 (±4.6), ALC 1.9 (±1.6), platelets 92.6 (±123.2). Incidence of probable IFI 2/95 (2.1%). No proven IFI cases identified. Clinical failure occurred in 37/95 (39%): 8 persistent febrile neutropenia, 29 due to suspected IFI. No MCF discontinuation due to adverse events. Conclusion Our findings suggest that prophylactic MCF is safe and effective in pts with newly diagnosed AML undergoing induction chemotherapy. Outcomes were similar to those of prophylactic posaconazole studies, indicating MCF may be considered as an alternative when interactions and adverse effects preclude use of posaconazole. Our study was limited by small numbers, retrospective, single-center design. Future opportunities include prospective trials of prophylactic MCF in this setting. Disclosures All Authors: No reported disclosures

scholarly journals Clinical Outcomes of Oral Suspension versus Delayed-Release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Jon P. Furuno ◽  
Gregory B. Tallman ◽  
Brie N. Noble ◽  
Joseph S. Bubalo ◽  
Graeme N. Forrest ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Hematologic Malignancies ◽  
Invasive Fungal Infections ◽  
Oral Suspension ◽  
European Organization ◽  
Delayed Release ◽  
Suspension Formulation ◽  
Eortc Criteria ◽  
Significant Difference ◽  
Release Tablet

ABSTRACT Posaconazole is used for prophylaxis for invasive fungal infections (IFIs) among patients with hematologic malignancies. We compared the incidence of breakthrough IFIs and early discontinuation between patients receiving delayed-release tablet and oral suspension formulations of posaconazole. This was a retrospective cohort study of patients receiving posaconazole between 1 January 2010 and 30 June 2016. We defined probable or proven breakthrough IFIs using the European Organization for Research and Treatment of Cancer (EORTC) criteria. Overall, 547 patients received 860 courses of posaconazole (53% received the oral suspension and 48% received the tablet); primary indications for prophylaxis were acute myeloid leukemia (69%), graft-versus-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indications between patients receiving the different formulations. The incidence and incidence rate of probable or proven IFIs were 1.6% and 3.2 per 10,000 posaconazole days, respectively. There was no significant difference in the rate of IFIs between suspension courses (2.8 per 10,000 posaconazole days) and tablet courses (3.7 per 10,000 posaconazole days) (rate ratio = 0.8, 95% confidence interval [CI] = 0.3 to 2.3). Of the 14 proven or probable cases of IFI, 8/14 had posaconazole serum concentrations measured, and the concentrations in 7/8 were above 0.7 μg/ml. Posaconazole was discontinued early in 15.5% of courses; however, the frequency of discontinuation was also not significantly different between the tablet (16.5%) and oral suspension (14.6%) formulations (95% CI for difference = −0.13 to 0.06). In conclusion, the incidence of breakthrough IFIs was low among patients receiving posaconazole prophylaxis and not significantly different between patients receiving the tablet formulation and those receiving the oral suspension formulation.

scholarly journals Incidence and Risk Factors for Breakthrough Invasive Mold Infections in Acute Myeloid Leukemia Patients Receiving Remission Induction Chemotherapy

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Heena P Patel ◽  
Anthony J Perissinotti ◽  
Twisha S Patel ◽  
Dale L Bixby ◽  
Vincent D Marshall ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Multivariable Analysis ◽  
Antifungal Prophylaxis ◽  
Remission Induction ◽  
Invasive Mold Infections ◽  
Acute Myeloid

Abstract Background Despite fungal prophylaxis, invasive mold infections (IMIs) are a significant cause of morbidity and mortality in patients with acute myeloid leukemia (AML) receiving remission induction chemotherapy. The choice of antifungal prophylaxis agent remains controversial, especially in the era of novel targeted therapies. We conducted a retrospective case–control study to determine the incidence of fungal infections and to identify risk factors associated with IMI. Methods Adult patients with AML receiving anti-Aspergillus prophylaxis were included to determine the incidence of IMI per 1000 prophylaxis-days. Patients without and with IMI were matched 2:1 based on the day of IMI diagnosis, and multivariable models using logistic regression were constructed to identify risk factors for IMI. Results Of the 162 included patients, 28 patients had a possible (n = 22), probable, or proven (n = 6) diagnosis of IMI. The incidence of proven or probable IMI per 1000 prophylaxis-days was not statistically different between anti-Aspergillus azoles and micafungin (1.6 vs 5.4, P = .11). The duration of prophylaxis with each agent did not predict IMI occurrence on regression analysis. Older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.004–1.081; P = .03) and relapsed/refractory AML diagnosis (OR, 4.44; 95% CI, 1.56–12.64; P = .003) were associated with IMI on multivariable analysis. Conclusions In cases that preclude use of anti-Aspergillus azoles for prophylaxis, micafungin 100 mg once daily may be considered; however, in older patients and those with relapsed/refractory disease, diligent monitoring for IMI is required, irrespective of the agent used for antifungal prophylaxis.

scholarly journals 1301. Breakthrough Invasive Fungal Infections based on CYP2C19 Levels in Patients Who were on Voriconazole as Primary Antifungal Prophylaxis in Acute Myeloid Leukemia (AML) undergoing Induction Chemotherapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S665-S665
Author(s):  
Hareesh v Singam ◽  
Yanina Pasikhova ◽  
Rod Quilitz ◽  
John N Greene ◽  
Aliyah Baluch
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Antifungal Prophylaxis ◽  
Invasive Fungal Infections ◽  
Cancer Center ◽  
Newly Diagnosed ◽  
Intermediate Metabolizers ◽  
Acute Myeloid

Abstract Background Voriconazole (Vori) is often used for prophylactic anti-fungal therapy in induction chemotherapy for Acute Myeloid Leukemia (AML) patients due to predictable absorption and an extended spectrum antifungal activity. Vori is metabolized predominately by CYP2C19 to metabolites with less antifungal activity. There has been a great interest in understanding CYP2C19 as it significantly affects drug metabolism and pharmacokinetics of numerous drugs including voriconazole. Approximately 39% of patients are genetically predicted to be CYP2C19 ultra-rapid or rapid metabolizers and thus are at an increased risk of breakthrough fungal infection. This study assesses the incidence of breakthrough invasive fungal infections (bIFI) at Moffitt Cancer Center based on CYP2C19 activity. bIFI is defined as new fungal infection while on vori, leading to treatment with liposomal amphotericin B, echinocandin, and/or different triazole. Methods This is a single-center retrospective analysis of patients who underwent induction chemotherapy for newly diagnosed AML and received voriconazole as the primary antifungal prophylaxis between July 2017 and June 2019. The patients enrolled were over 18 years old and did not have a history of stem cell transplant or solid organ transplant, Human Immunodeficiency Virus, relapsed AML or received systematic antifungal therapy 30 days prior. CYP2C19 were checked for each of the patients between July 2017 to June 2019 who were undergoing induction chemotherapy for newly diagnosed AML. It was checked within one week of admission. The patients were categorized as rapid metabolizers, intermediate metabolizers, normal metabolizers, and unknown CYP2C19. Results There was an incidence of 20.2% (18/89) bIFI in patients who were on Vori in this study. Of these patients with bIFI infections, 15.7% (3/19) of patients were rapid metabolizers, 14.7% (5/34) were normal metabolizers, 28.5% (4/14) were intermediate metabolizers and 0% (0/3) were poor metabolizers. There were 31% (6/19) breakthrough infections in patients with unknown CYP2C19 characteristics. Conclusion There is no significant statistical difference (p=0.6) among CYP2C19 categories with respect to breakthrough of invasive fungal infections at Moffitt Cancer Center between July 2017 - June 2019. Disclosures Rod Quilitz, Pharm D., Astellas (Advisor or Review Panel member)

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