Isavuconazonium

CRESEMBA

What it isProdrug of the triazole isavuconazole; invasive aspergillosis and mucormycosis.

Why this oneIt covers Mucorales with predictable absorption and uniquely shortens rather than prolongs QT among azoles.

What limits itFamilial short-QT syndrome is a contraindication; hepatotoxicity and CYP3A4 interactions still require review.

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

Cost, est. cash$300–$5,000/dose or month

Generic entry2031 est.

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk1 / 4

Legacy pregnancy categoryUnknown / historical label unavailable

Defining liabilityHepatotoxicity and clinically important CYP/QT interactions; organ toxicity varies markedly by agent.