isavuconazole
Brand: Cresemba
Prototype: voriconazole
Drug Class: triazole antifungal
Drug Family: antifungal
Subclass: extended-spectrum triazole (anti-Aspergillus, anti-Mucorales)
Organ Systems: infectious-disease
Mechanism of Action
Inhibits fungal CYP51; active against Aspergillus and Mucorales; prodrug isavuconazonium sulfate rapidly converted to active isavuconazole; fewer drug interactions than voriconazole; QTc-shortening rather than prolonging effect (unique).
fungal CYP51 (14-alpha-demethylase)
Indications
- invasive aspergillosis (alternative to voriconazole)
- invasive mucormycosis
Contraindications
- isavuconazole hypersensitivity
- familial short QT syndrome
- concurrent strong CYP3A4 inducers (rifampin, carbamazepine)
- concurrent ketoconazole (strong CYP3A4 inhibitor)
Adverse Effects
Common
- nausea
- vomiting
- diarrhea
- headache
- liver test abnormalities
Serious
- hepatotoxicity
- QTc shortening (caution in familial short QT syndrome)
- infusion-related reactions (IV)
Pharmacokinetics (ADME)
| Absorption | prodrug isavuconazonium converted to isavuconazole; oral bioavailability ~98%; not significantly affected by food |
| Distribution | large Vd (450 L); extensive tissue distribution |
| Metabolism | CYP3A4 and CYP3A5 substrate; also CYP3A4 inhibitor (moderate) |
| Excretion | fecal (>46%) and renal (<1% unchanged) |
| Half-life | 130 hours |
| Onset | rapid |
| Peak | 2–3 hours (oral) |
| Duration | once-daily (after loading) |
| Protein Binding | >99% |
| Vd | very large (450 L) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| tacrolimus/cyclosporine | moderate CYP3A4 inhibition increases levels; monitor TDM | major |
| rifampin/carbamazepine | strong CYP3A4 induction reduces isavuconazole levels by >50%; contraindicated | major |
| midazolam | CYP3A4 inhibition increases midazolam by ~2-fold; use lowest effective benzodiazepine dose | moderate |
Nursing Considerations
- Oral formulation has near-complete bioavailability and can be taken with or without food — a significant practical advantage over posaconazole suspension.
- Isavuconazole shortens the QTc interval — monitor ECG; contraindicated in patients with familial short QT syndrome.
- Loading dose (200 mg three times daily for 2 days) then once-daily maintenance dosing; verify correct frequency.
- No dose adjustments needed for mild-to-moderate hepatic impairment — an advantage in patients with liver disease.
Clinical Pearls
- Unlike all other triazoles, isavuconazole shortens rather than prolongs the QTc interval — while usually benign, this distinguishes it pharmacologically and requires ECG awareness in patients with short QT syndrome.
- Isavuconazole is one of only two antifungals (with posaconazole) with FDA approval for mucormycosis treatment, making it valuable for this serious infection that is unresponsive to most antifungals.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.