Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single‐center experience

Vu, Christine; Rana, Meenakshi; Jacobs, Samantha; Saunders-Hao, Patricia

doi:10.1111/tid.13469

Cited by 17 publications

(21 citation statements)

References 18 publications

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“…Two patients had breakthrough fungal infections even with high levels of s-ISZ. Breakthrough fungal infections during ISZ prophylaxis or treatment have also been reported by others [ 7 , 8 , 9 , 10 , 11 , 32 , 33 ]. Breakthrough fungal infections during ISZ prophylaxis in hematological patients when s-ISZ was within the therapeutic range have also been observed [ 9 ].…”

Section: Discussionsupporting

confidence: 58%

“…In addition to treatment, ISZ was found to be safe as prophylaxis in a clinical trial with acute myeloid leukemia and myelodysplastic syndrome patients of which almost half received targeted treatments such as venetoclax and FLT3 inhibitors [7]. Isavuconazole as prophylaxis has also been reported in other studies [8][9][10][11] as well as the use of ISZ in children [12] and patients with chronic pulmonary aspergillosis (CPA) [13,14]. Although ISZ has been used as prophylaxis, this is a non-approved and off-label intervention.…”

Section: Introductionmentioning

confidence: 94%

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Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

et al. 2021

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Isavuconazole (ISZ) is used in the treatment of aspergillosis and mucormycosis. The purpose of this study was to evaluate the therapeutic drug monitoring (TDM) of ISZ samples from a clinical setting performed at Statens Serum Institut. Materials/methods: Isavuconazole serum concentrations were determined by fluorescent detection on a UHPLC. Serum-ISZ (s-ISZ) results were included and compared to those of serum-voriconazole (s-VRZ) in a 33 month period from March 2017. Clinical data were obtained for patients receiving ISZ. The therapeutic range was initially 2–10 mg/L, but was adjusted to 2–5 mg/L during the study period except for selected patients with Mucorales infections who received off-label doses of ISZ. Results: A total of 273 s-ISZ and 1242 s-VRZ measurements from 35 and 283 patients, respectively, were included. Seventeen patients had received both ISZ and VRZ with TDM within the study period. The median s-ISZ was 4.3 mg/L (0.5–15.4 mg/L) with 83% of measurements within the therapeutic index. The median s-VRZ was 2.6 mg/L (0.2–21.9 mg/L) with 67% of measurements within the therapeutic index. The median intra-/interindividual coefficient of variation (CV) was 43.4%/54.8% for ISZ compared to 53.2%/83.3% for VRZ. For patients receiving ISZ, the adverse events were mostly gastroenteric and few drug–drug interactions were observed. Furthermore, immediate change from ISZ to VRZ treatment seemed to lead to prolonged metabolism of ISZ with detection up to 35 days after discontinuation. Conclusions: The majority of patients achieved s-ISZ levels well within the therapeutic range with less intra/interindividual CV than patients receiving VRZ.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 94%

Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

et al. 2021

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“…However, despite adequate exposure, breakthrough infections remain a matter of concern, particularly given the growing use of ISZ for prophylaxis. 280 Outside the classical background of immunocompromised patients, other fields need to be taken into account, particularly diabetes and the emergence of rhinocerebral mucormycosis.…”

Section: Isz Placementioning

confidence: 99%

Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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“…In patients with high risk of invasive fungal disease, such as acute myeloid leukemia or transplant, antifungal prophylaxis has become a standard of care. Although isavuconazole does not have a formal indication for mold-active prophylaxis, it has been used in several studies, mainly in patients with hematological malignancies, and in lung transplant recipients in one study [ 33 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. In these settings, the breakthrough rate of proven or probable IFD was in median 6%, ranging from 0 to 18% [ 33 , 62 , 63 , 64 , 65 , 66 , 67 ].…”

Section: Prophylaxis Of Capa In Icumentioning

confidence: 99%

“…Although isavuconazole does not have a formal indication for mold-active prophylaxis, it has been used in several studies, mainly in patients with hematological malignancies, and in lung transplant recipients in one study [ 33 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. In these settings, the breakthrough rate of proven or probable IFD was in median 6%, ranging from 0 to 18% [ 33 , 62 , 63 , 64 , 65 , 66 , 67 ]. The breakthrough infections were also observed in patients with adequate isavuconazole levels, both in the aforementioned study and in a separate report [ 68 , 69 ].…”

Section: Prophylaxis Of Capa In Icumentioning

confidence: 99%

Isavuconazole for COVID-19-Associated Invasive Mold Infections

Ullah

Sepulcri

Mikulska

2022

JoF

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Isavuconazole is a broad-spectrum antifungal drug recently approved as a first-line treatment for invasive aspergillosis and as a first or alternative treatment for mucormycosis. The purpose of this review was to report and discuss the use of isavuconazole for the treatment of COVID-19-associated aspergillosis (CAPA), and COVID-19-associated mucormycosis (CAM). Among all studies which reported treatment of CAPA, approximately 10% of patients were reportedly treated with isavuconazole. Considering 14 identified studies that reported the use of isavuconazole for CAPA, isavuconazole was used in 40% of patients (95 of 235 treated patients), being first-line monotherapy in over half of them. We identified six studies that reported isavuconazole use in CAM, either alone or in combination therapy. Overall, isavuconazole was used as therapy in 13% of treated CAM patients, frequently as combination or sequential therapy. The use of isavuconazole in CAPA and CAM is complicated by the challenge of achieving adequate exposure in COVID-19 patients who are frequently obese and hospitalized in the ICU with concomitant renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO). The presence of data on high efficacy in the treatment of aspergillosis, lower potential for drug–drug interactions (DDIs) and for subtherapeutic levels, and no risk of QT prolongation compared to other mold-active azoles, better safety profile than voriconazole, and the possibility of using an intravenous formulation in the case of renal failure are the advantages of using isavuconazole in this setting.

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Isavuconazole for the prophylaxis and treatment of invasive fungal disease: A single‐center experience

Cited by 17 publications

References 18 publications

Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

Therapeutic Drug Monitoring of Isavuconazole: Serum Concentration Variability and Success Rates for Reaching Target in Comparison with Voriconazole

Antifungal Drugs TDM: Trends and Update

Isavuconazole for COVID-19-Associated Invasive Mold Infections

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