Triazole Antifungal (Aspergillosis / Mucormycosis) Pregnancy: Avoid — teratogenic in animal studies. Use alternative antifungal (liposomal amphotericin B preferred in pregnancy for invasive fungal infections). Specialist ID input required.

Isavuconazole

Brand names: Cresemba

Adult dose

Dose: Loading: 200 mg every 8 hours for 6 doses (48 hours), then 200 mg once daily maintenance

Route: Oral or Intravenous (bioavailability ~98% — IV and oral doses identical)

Frequency: Every 8 hours × 6 doses (loading), then once daily

Max: 200 mg/day (maintenance)

Invasive aspergillosis (first-line alternative to voriconazole) and invasive mucormycosis (first-line alongside amphotericin B). Prodrug — isavuconazonium sulphate cleaved to active isavuconazole. High oral bioavailability means seamless IV-to-oral switch. QTc SHORTENING (not prolongation) — class-specific effect. Source: BNF 90; ESCMID/ECMM Mucormycosis Guidelines 2019.

Paediatric dose

Dose: Not licensed under 18 years N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not licensed for paediatric fungal infections. Off-label use under specialist guidance.

Dose adjustments

Renal

No dose adjustment required for any level of renal impairment. IV formulation (sulfobutylether-beta-cyclodextrin vehicle) accumulates in severe renal impairment — switch to oral when eGFR <30 mL/min.

Hepatic

Mild-moderate hepatic impairment: no dose adjustment. Severe hepatic impairment (Child-Pugh C): not studied — use with caution. Voriconazole has more hepatotoxicity than isavuconazole — isavuconazole preferred in pre-existing hepatic disease.

Paediatric weight-based calculator

Patient weight (kg)

Not licensed for paediatric fungal infections. Off-label use under specialist guidance.

Clinical pearls

Mucormycosis — first-line alongside liposomal amphotericin: isavuconazole is the ONLY triazole with a licence for mucormycosis (Rhizopus, Mucor, Lichtheimia). Voriconazole and posaconazole are NOT active against Mucorales. VITAL trial showed isavuconazole non-inferior to amphotericin B in mucormycosis. Used as step-down after initial amphotericin B in responding patients.
Voriconazole vs isavuconazole for aspergillosis: SECURE trial showed isavuconazole non-inferior to voriconazole for invasive aspergillosis. Advantages: (1) no TDM required, (2) more predictable PK, (3) no phototoxicity, (4) less hepatotoxicity, (5) no hallucinations/visual disturbances, (6) oral/IV seamless switch, (7) no food restriction. ESCMID 2017 guidelines recommend either as first-line.
QTc shortening — the opposite of all other antifungals: isavuconazole shortens the QTc by average 13–15 ms. This is safe for most patients but is a relative contraindication in inherited short QT syndrome (rare). This is the only antifungal that does NOT prolong QTc — it can replace voriconazole/posaconazole/fluconazole in patients with prolonged QTc at baseline.
No therapeutic drug monitoring (TDM) needed: unlike voriconazole (highly variable PK; TDM mandatory) and posaconazole (food-dependent absorption; TDM recommended), isavuconazole has predictable linear PK and does not routinely require TDM. Exceptions: suspected non-adherence, drug interactions, treatment failure.
Oral bioavailability ~98%: IV-to-oral switch is seamless at identical dose. Unlike IV posaconazole (high-risk patients only) or voriconazole (oral doses differ from IV), isavuconazole 200 mg IV = 200 mg oral — simplifies step-down. Source: BNF 90; Maertens et al. Lancet 2016 (SECURE trial); ESCMID/ECMM Mucormycosis Guidelines 2019; MHRA SPC Cresemba.

Contraindications

Concurrent strong CYP3A4 inducers (rifampicin, carbamazepine, St John's Wort): reduce isavuconazole levels by 97% — contraindicated
Concurrent high-dose ritonavir (>200 mg twice daily): increases isavuconazole — avoid
Familial short QT syndrome (isavuconazole shortens QTc — theoretically worsens)
Hypersensitivity to isavuconazole or related azoles

Side effects

Nausea, vomiting, diarrhoea, abdominal pain (most common)
Elevated liver transaminases (less than voriconazole — advantage in hepatotoxicity risk)
Hypokalaemia, hypomagnesaemia (electrolyte monitoring)
QTc shortening (unique among antifungals — averages 13–15 ms shortening; usually clinically benign; contraindicated only in congenital short QT syndrome)
Peripheral oedema
Rash (less photosensitivity than voriconazole)

Interactions

Strong CYP3A4 inducers (rifampicin, efavirenz, carbamazepine): reduce isavuconazole AUC by >90% — contraindicated
CYP3A4 substrates (tacrolimus, ciclosporin, sirolimus): isavuconazole is moderate CYP3A4 inhibitor — increases immunosuppressant levels; reduce dose and monitor trough levels
Digoxin: P-gp inhibition — increased digoxin levels; monitor
Metformin: possible increased exposure
Hormonal contraceptives: reduced efficacy (CYP3A4 induction) — use additional contraceptive method

Monitoring

Liver function tests (ALT, AST) at baseline, 2 weeks, then monthly (less hepatotoxic than voriconazole but monitor)
Serum electrolytes (potassium, magnesium) — replace proactively
Clinical response and CT/MRI imaging (aspergillosis — chest CT at 2 weeks and 4 weeks to assess response)
No routine TDM required (unlike voriconazole) — check in treatment failure or suspected interaction
ECG (QTc — note shortening, not prolongation; monitor in borderline short QT syndrome)

Reference: BNFc; BNF 90; Maertens et al. Lancet 2016 (SECURE); Marty et al. Lancet Infect Dis 2016 (VITAL — mucormycosis); ESCMID/ECMM Mucormycosis Guidelines 2019; MHRA SPC Cresemba. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Pathways