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Pharmacology

Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis

Chris Kosmidis, Akan Otu, Caroline B. Moore, Malcolm D. Richardson, Riina Rautemaa-Richardson
Chris Kosmidis
aNational Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
bDivision of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom
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Akan Otu
aNational Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
cDepartment of Infection and Travel Medicine, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
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Caroline B. Moore
dMycology Reference Centre Manchester, ECMM Excellence Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
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Malcolm D. Richardson
bDivision of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom
dMycology Reference Centre Manchester, ECMM Excellence Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
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Riina Rautemaa-Richardson
aNational Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
bDivision of Infection, Immunity, and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, United Kingdom
dMycology Reference Centre Manchester, ECMM Excellence Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
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DOI: 10.1128/AAC.01511-20
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ABSTRACT

Isavuconazole is the newest triazole antifungal, and it displays a favorable pharmacokinetic and safety profile. Less is known about its long-term use in immunocompetent hosts. We performed a retrospective service evaluation of isavuconazole therapeutic drug monitoring in patients with chronic pulmonary aspergillosis. Adverse events (AEs) and dose adjustments made during routine clinical practice were recorded, and AEs were classified based on Common Terminology Criteria for Adverse Events v5.0. Forty-five patients (mean age, 64 years) had 285 isavuconazole blood drug levels measured (mean level, 4.1 mg/liter). A total of 117 measurements (41%) were performed on patients on a 100-mg daily dose instead of 200 mg, and all had blood levels of >1 mg/liter. Age (P = 0.012) and a daily dose of 200 mg versus 100 mg (P = 0.02) were independent predictors of levels of >6 mg/liter. AEs were recorded for 25 patients (56%). The mean drug level at the first measurement was 5.5 ± 2 mg/liter for patients reporting AEs, compared with 4.2 ± 1.7 mg/liter for those not reporting AEs (P = 0.032). The cutoff threshold best predictive of an AE was 4.6 mg/liter (area under the concentration-time curve, 0.710). Sixteen patients (36%) discontinued isavuconazole therapy due to AEs. Twenty-six patients (58%) continued on isavuconazole beyond 6 months. Asthma (P = 0.022) and a daily dose of 200 mg versus 100 mg (P = 0.048) were associated with AEs of grade 2 or higher. A reduced daily dose (100 mg versus 200 mg) of isavuconazole resulted in satisfactory drug levels in a substantial number of patients; it was better tolerated and enabled continuation of therapy for prolonged periods.

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Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis
Chris Kosmidis, Akan Otu, Caroline B. Moore, Malcolm D. Richardson, Riina Rautemaa-Richardson
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01511-20; DOI: 10.1128/AAC.01511-20

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Isavuconazole Therapeutic Drug Monitoring during Long-Term Treatment for Chronic Pulmonary Aspergillosis
Chris Kosmidis, Akan Otu, Caroline B. Moore, Malcolm D. Richardson, Riina Rautemaa-Richardson
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01511-20; DOI: 10.1128/AAC.01511-20
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KEYWORDS

TDM
aspergillosis
chronic pulmonary aspergillosis
isavuconazole
pharmacokinetics

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