Antimicrobials
Isavuconazole
Guidelines for use
Restricted to Infectious Diseases
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1. Spectrum of Activity
Active against:
- Candida species: albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei
- Aspergillus species
- Dimorphic fungi: Histoplasma, Blastomyces, Cocciodiodes (limited clinical experience
- Mucorales
Not active against:
- Fusarium species
2. Clinical Usage
- Invasive Aspergillosis: second-line to voriconazole if/when:
- Significant intolerance (e.g. visual side effects, hepatotoxicity, QT prolongation)
- Significant and severe voriconazole-associated drug interactions
- Contraindications to voriconazole (e.g. prolonged QT at baseline)
- Mucormycosis: second-line to amphotericin if/when:
- Oral stepdown option from liposomal amphotericin
- Contraindications to amphotericin (treatment-emergent or baseline)
3. Inappropriate Uses
- Treatment of fungal infections for which there are narrower options (e.g. fluconazole, voriconazole)
4. Significant Interactions
Note: Isavuconazole is both a substrate and inhibitor of several clinically-relevant CYP 450 enzymes. The following table highlights commonly-encountered drug interactions, but is not inclusive. Always verify drug interactions.
|
Drug |
Recommendation |
|
Increases isavuconazole level |
|
|
Lopinavir/ritonavir |
Use with caution (~2 fold increase in isavuconazole levels) |
|
Ketoconazole |
Contraindicated (~5-fold increase in isavuconazole levels) |
|
Decreases isavuconazole level |
|
|
Rifampin |
Contraindicated |
|
Carbamazepine |
|
|
Long-acting barbiturates (e.g. phenobarbital) |
|
|
St. John’s Wort |
|
|
Levels increased by isavuconazole |
|
|
Sirolimus |
Use with caution. Monitor serum levels of these drugs and adjust dose when given with isavuconazole |
|
Tacrolimus |
|
|
Cyclosporine |
|
|
Mycophenolate mofetil |
|
|
Digoxin |
|
|
Colchicine |
Use with caution. May require dose adjustment. |
|
Dabigatran |
|
|
Atorvastatin |
No dose adjustment recommended when given with isavuconazole; monitor patient |
|
Midazolam |
|
|
Levels decreased by isavuconazole |
|
|
Bupropion |
Use with caution. Dose increase of bupropion may be necessary |
|
Lopinavir/ritonavir |
Use with caution |
Adapted from: CID. 2015:61(15):1561
5. Precautions
- For use in pregnancy and breastfeeding, see Safe Use of Antibacterial Agents: Pregnancy & Breastfeeding
- Avoid use in patients with familial short QT syndrome
- Use with caution in patients with severe hepatic impairment (Child Pugh Class C)
6. Adverse Effects
- Common: headache, GI upset (nausea, vomiting, diarrhea), transaminitis (usually mild and reversible upon cessation of drug), rash
- Rare: hepatoxicity, hypokalemia, peripheral edema, infusion reactions (IV formulation)
7. Dosage
Note: The oral bioavailability of oral isavuconazole is > 95%. IV therapy should be reserved for patients with impaired gut absorption or for those unable to swallow
- Usual Dosage: 200 mg po/IV q8h x 6 doses, then 200 mg po/IV q24h
- Renal Dosage: no dose reduction required
- Dosage in Hepatic Impairment:
- Child-Pugh A or B: no dose adjustment required; monitor transaminases
- Child-Pugh C: use with caution (safety not studied)
8. Monitoring
- Transaminases – several times weekly
- Potassium – several times weekly
9. Administration
- For preparation/administration, see IV drug monograph
References:
- Clin Infect Dis.2015:61(15):1561
- Clin Pharmacol Drug Dev. 2017;6(1):93-101
- Cresemba™ Drug Monograph: https://pdf.hres.ca/dpd_pm/00048808.PDF
Last updated December 12, 2022
