Isavuconazole

CRESEMBA

What it isTriazole antifungal, the active form of isavuconazonium; aspergillosis and mucormycosis.

Why it mattersIt covers Mucorales like posaconazole with predictable absorption and no QT prolongation.

What it changesIt SHORTENS QT, so it is contraindicated in familial short QT syndrome. A moderate CYP3A4 inhibitor.

FDA-approved for

FDA dosing	Population	Start	Target	Max
Invasive aspergillosis	Adults	Loading 372 mg (=200 mg isavuconazole) q8h ×6 doses (48 h)	Maintenance 372 mg QD
Invasive mucormycosis	Adults	Loading 372 mg q8h ×6 doses (48 h)	Maintenance 372 mg QD
Invasive aspergillosis/mucormycosis	Peds ≥1 yr	IV loading 15 mg/kg (<3 yr) or 10 mg/kg (≥3 yr) q8h ×6 doses	Maintenance same dose QD	372 mg per dose

Renal No adjustment needed (mild/moderate/severe incl. ESRD)

Hepatic No adjustment for mild-moderate (Child-Pugh A/B); not studied in severe (C) — use only if benefits outweigh risks, with monitoring

Start maintenance dose 12-24 h after the last loading dose

Capsules: swallow whole; do not chew, crush, dissolve, or open; take with or without food
IV: infuse over ≥1 hour through an in-line filter (0.2-1.2 micron); do not give as a bolus; do not co-infuse other drugs
Switching between IV and oral is acceptable (bioequivalent); no loading dose needed when switching

Coadministration with strong CYP3A4 inhibitors (e.g., ketoconazole, high-dose ritonavir)
Coadministration with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort, long-acting barbiturates)
Familial short QT syndrome

Hepatic adverse reactions — evaluate liver tests at baseline and during therapy
Infusion-related reactions (IV) — discontinue infusion if they occur
Hypersensitivity — anaphylaxis (fatal reported) and severe skin reactions (e.g., SJS)
Embryo-fetal toxicity — advise effective contraception
Drug particulates — administer IV through an in-line filter

Pregnancy May cause fetal harm based on animal studies (perinatal mortality, skeletal abnormalities); advise of risk and use contraception.

Lactation No human data; discontinue breastfeeding during treatment with CRESEMBA.

NO BOXED WARNINGS

Principal riskContraindicated in familial short QT syndrome

Direct muscarinic antagonism0 / 4