Isavuconazole Concentration in Real-World Practice: Consistency with Results from Clinical Trials

Andes, David R.; Kovanda, Laura; Desai, Amit; Kitt, Therese M; Zhao, Miao; Walsh, Thomas J.

doi:10.1128/aac.00585-18

Cited by 108 publications

(80 citation statements)

References 23 publications

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“…Several findings are particularly noteworthy. First, there was moderate interpatient variability in ISA AUC 0 -24 h (CV of 51%), which was comparable to those described in previous ISA PK studies (15)(16)(17). Second, the plasma trough concentration was highly correlated with the ISA AUC 0 -24 h (R 2 ϭ 0.94; P Ͻ 0.0001).…”

Section: Discussionsupporting

confidence: 82%

“…The interpatient variabilities in ISA AUC 0 -24 h and C trough (CV of 51% and 59%, respectively) were similar to the variability for AUC previously reported in ISA clinical trials or in clinical samples (CV of 68%), where ISA was given either i.v. or orally (15)(16)(17). The range of ISA exposure in our patients was striking, with 10-fold and 18-fold differences in low and high values for AUC 0 -24 h (15.16 to 155.54 g · h/ml) and C trough (0.35 to 6.37 g/ml), respectively.…”

Section: Discussionmentioning

confidence: 66%

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Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients

Clancy

Rivosecchi

et al. 2018

Antimicrob Agents Chemother

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Isavuconazole may be useful in treating and preventing fungal infections in solid-organ transplant (SOT) recipients due to its safety profile and activity against Aspergillus and some Mucorales. Isavuconazole has favorable pharmacokinetics based on clinical trials in various patient populations, but data are limited in SOT recipients. We evaluated the steady-state pharmacokinetics of isavuconazole in 26 SOT recipients receiving the drug intravenously for prophylaxis. There was moderate interpatient variability in isavuconazole pharmacokinetic parameters (coefficients of variation of 51% for the area under the plasma concentration-versus-time curve [AUC] and 59% for the trough plasma concentration [C trough ]). AUC and steady-state C trough were significantly lower in women, patients with a body mass index of Ն18.5 kg/m 2 , and those receiving hemodialysis. Trough plasma concentrations were highly correlated with AUCs (R 2 ϭ 0.94) and can serve as a suitable measure of isavuconazole exposure in patients. In conclusion, moderate interpatient variability in isavuconazole exposure, the identification of factors associated with lower exposure, the recognition that C trough is a surrogate marker for AUC, and the availability of a simple analytical method suggest that therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least some SOT recipients. Future studies are needed to correlate isavuconazole exposure with patients' clinical outcomes and to determine the clinical role of TDM.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 66%

Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients

Clancy

Rivosecchi

et al. 2018

Antimicrob Agents Chemother

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“…Isavuconazonium 372 mg every eight hours was also given in combination with liposomal amphotericin B and tapered to one dose daily. Unlike posaconazole, isavuconazole does not require routine serum level monitoring because therapeutic levels are reached in most patients with standard dosing regiments [10].…”

Section: Discussionmentioning

confidence: 99%

An Aggressive Case of Mucormycosis

Tran

Schmit

2020

Cureus

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“…ISA is approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the treatment of adults (age, Ͼ18 years) with invasive aspergillosis (IA) and invasive mucormycosis (6)(7)(8)10). ISA shows a favorable linear pharmacokinetic and safety profile with excellent bioavailability after oral administration with no relevant food or gastric pH effect, suggesting that TDM may not be necessary (11)(12)(13).…”

mentioning

confidence: 99%

A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation

Decembrino

Perruccio

Zecca

et al. 2020

Antimicrob Agents Chemother

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We analyzed the use of isavuconazole (ISA) as treatment or prophylaxis for invasive fungal disease (IFD) in children with hemato-oncologic diseases. A multicentric retrospective analysis was performed among centers belonging to the Italian Association for Pediatric Hematology and Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by a high-performance liquid chromatography-tandem mass spectrometry (HLPC-MS/MS) assay. Twenty-nine patients were studied: 10 during chemotherapy and 19 after allogeneic hematopoietic stem cell transplantation (HSCT). The patients consisted of 20 males and 9 females with a median age of 14.5 years (age range, 3 to 18 years) and a median body weight of 47 kg (body weight range, 15 to 80 kg). ISA was used as prophylaxis in 5 patients and as treatment in 24 cases (20 after therapeutic failure, 4 as first-line therapy). According to European Organization for Research and Treatment of Cancer (EORTC) criteria, we registered 5 patients with proven IFD, 9 patients with probable IFD, and 10 patients with possible IFD. Patients with a body weight of <30 kg received half the ISA dose; the others received ISA on the adult schedule (a 200-mg loading dose every 8 h on days 1 and 2 and a 200-mg/day maintenance dose); for all but 10 patients, the route of administration switched from the intravenous route to the oral route during treatment. ISA was administered for a median of 75.5 days (range, 6 to 523 days). The overall response rate was 70.8%; 12 patients with IFD achieved complete remission, 5 achieved partial remission, 5 achieved progression, and 3 achieved stable IFD. No breakthrough infections were registered. PK monitoring of 17 patients revealed a median ISA steady-state trough concentration of 4.91 mg/liter (range, 2.15 to 8.54 mg/liter) and a concentration/dose (in kilograms) ratio of 1.13 (range, 0.47 to 3.42). Determination of the 12-h PK profile was performed in 6 cases. The median area under the concentration-time curve from 0 to 12 h was 153.16 mg·h/liter (range, 86.31 to 169.45 mg·h/liter). Common Terminology Criteria for Adverse Events grade 1 to 3 toxicity (increased transaminase and/or creatinine levels) was observed in 6 patients, with no drug-drug interactions being seen in patients receiving immunosuppressants. Isavuconazole may be useful and safe in children with hemato-oncologic diseases, even in the HSCT setting. Prospective studies are warranted.

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Isavuconazole Concentration in Real-World Practice: Consistency with Results from Clinical Trials

Cited by 108 publications

References 23 publications

Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients

Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients

An Aggressive Case of Mucormycosis

A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation

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