Isavuconazole Treatment for Invasive Aspergillosis

First-Line Treatment Status

The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the Infectious Diseases Society of America (IDSA) recommend isavuconazole as a first-line treatment option for invasive aspergillosis, with an AI-level recommendation (strong recommendation, high-quality evidence), due to its efficacy equivalent to voriconazole but with superior tolerability and fewer adverse effects 1, 2, 3, 4, 5, 6
The IDSA guidelines position isavuconazole as a primary treatment option based on demonstrated non-inferiority to voriconazole in the pivotal SECURE trial 3, 6

The phase III SECURE trial demonstrated non-inferiority of isavuconazole to voriconazole for primary treatment of invasive mold disease (primarily aspergillosis), with comparable survival and clinical response rates in the intent-to-treat population 6, 3
Isavuconazole showed fewer drug-related treatment-emergent adverse events compared to voriconazole, making it better tolerated 6, 3
The drug is effective for treating invasive aspergillosis in voriconazole-susceptible isolates (EUCAST MIC ≤1 mg/L) 1, 4

Isavuconazole demonstrates lower MICs compared to itraconazole and voriconazole for certain Aspergillus fumigatus complex species, specifically A. lentulus and A. udagawae 7, 1, 4
Susceptibility testing for isavuconazole should be performed separately if this agent is to be used, as MICs may differ from other azoles despite correlation 7, 1, 4

The IDSA guidelines note that isavuconazole has a superior adverse event profile compared to voriconazole, with notably less hepatotoxicity, neuro-visual toxicity, and no QTc prolongation 5
Isavuconazole has reduced drug-drug interactions relative to voriconazole, though interactions with CYP3A4 substrates still require monitoring 5

The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommends single or sequential monotherapy with isavuconazole for proven, probable, possible, and putative COVID-19 Associated Pulmonary Aspergillosis (CAPA) (strong recommendation, low-quality evidence) 8
Isavuconazole is listed alongside voriconazole, posaconazole, and liposomal amphotericin B as appropriate first-line options for CAPA treatment by the ESCMID 8
The IDSA guidelines recommend isavuconazole for treatment of invasive aspergillosis due to species showing high amphotericin B MICs, such as A. terreus and A. flavus 1, 4

The IDSA guidelines recommend treatment should continue for a minimum of 6-12 weeks, dependent on degree and duration of immunosuppression, site of disease, and evidence of disease improvement 3, 9
Treatment must continue throughout the immunosuppression period until complete resolution of clinical and radiographic findings 9
The IDSA guidelines suggest that while therapeutic drug monitoring is less established for isavuconazole than voriconazole, monitoring should be considered in refractory disease or when drug interactions are anticipated 5

The ESCMID guidelines note that isavuconazole susceptibility must be tested separately if this agent is chosen, as MICs can differ from other azoles despite correlation 7, 1, 4
The IDSA guidelines recommend not using isavuconazole as monotherapy for isolates with voriconazole MIC >2 mg/L without susceptibility confirmation, as cross-resistance is likely 1, 4
The IDSA guidelines suggest not overlooking the need to adjust dosing of concomitant CYP3A4 substrates (tacrolimus, cyclosporine, sirolimus) despite isavuconazole having fewer interactions than voriconazole 5