Invasive Aspergillosis Treatment Guidelines

Introduction to Isavuconazol

Isavuconazol is indicated as a first-line treatment for invasive aspergillosis in most patients, offering an equivalent alternative to voriconazol with a better safety and tolerability profile, as recommended by the Infectious Diseases Society of America and the European Society of Clinical Microbiology and Infectious Diseases 1, 2
Isavuconazol is a suitable treatment option for invasive aspergillosis in patients with hematological neoplasias, neutropenia, and recipients of hematopoietic stem cell transplants, according to the European Society of Clinical Microbiology and Infectious Diseases 2, 1

The recommended dosage of isavuconazol is a loading dose of 200 mg IV every 8 hours for 2 days (6 doses), followed by a maintenance dose of 200 mg IV or orally once daily, as suggested by the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America 2, 1
Alternative dosing includes a loading dose of 400 mg every 12 hours (2 doses), followed by 200-300 mg every 12 hours, with IV dosing of 6 mg/kg every 12 hours (2 doses), followed by 3-4 mg/kg every 12 hours 3, 4

Therapeutic monitoring of serum levels is recommended in cases of treatment failure, drug interactions, or suspected toxicity (Grade C-III), according to the European Society of Clinical Microbiology and Infectious Diseases 2

For first-line treatment, voriconazol or isavuconazol are recommended (A-I) by the Infectious Diseases Society of America, with a preference for isavuconazol in patients with renal insufficiency, risk of hepatic toxicity, polypharmacy, risk of QTc prolongation, or predisposition to visual or cutaneous adverse effects 1
Isavuconazol is suggested as a rescue therapy in cases of failure or intolerance to voriconazol, along with lipid formulations of amphotericin B, echinocandins (caspofungin, micafungin), and consideration of combination therapy in refractory cases, based on guidelines from the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America 2, 1
Isavuconazol has a better safety profile than voriconazol, with fewer treatment-related adverse events (42% vs 60%, p<0.001), including lower frequencies of hepatobiliary, ocular, and cutaneous disorders, and it does not prolong the QTc interval, but rather shortens it 5
The choice between isavuconazol and voriconazol should consider the patient's renal function, hepatic function, and potential for drug interactions, with isavuconazol preferred in patients with renal insufficiency, hepatic toxicity risk, poly-medication, QTc prolongation risk, or predisposition to visual or cutaneous adverse effects 5, 3, 4

Characteristic	Isavuconazol	Voriconazol
Renal insufficiency	No dose adjustment needed	Dose reduction required in severe renal insufficiency
Hepatic insufficiency	Better hepatic safety profile	Dose reduction required in mild to moderate hepatic insufficiency
Drug interactions	Lower potential for interactions	Numerous and significant interactions
QTc interval	Shortens the QTc interval	Prolongs the QTc interval
Adverse events	Fewer treatment-related adverse events (42% vs 60%, p<0.001)	Higher frequency of hepatobiliary, ocular, and cutaneous disorders