Isavuconazole

Background

Mechanism of Action

• Azole antifungal that inhibits lanosterol 14-α demethylase in the peptidoglycan synthesis pathway

Spectrum of Activity

• Active against Candida, Cryptococcus, Aspergillus including Aspergillus flavus, Aspergillus fumigatus, and Aspergillus niger, and Mucorales
• Indications include Chromoblastomycosis, Cladophialophora, Coccidioides immitis

Breakpoints

Species	ECOFF (mg/L)	Breakpoints (μg/mL)				Breakpoints (mm)
		S	I	SDD	R	S	I	SDD	R
Candida albicans
Candida glabrata
Candida krusei
Candida parapsilosis
Candida tropicalis
Cryptococcus neoformans
Cryptococcus gattii
Aspergillus flavus	2	—			—
Aspergillus fumigatus	2	≤1			>1
Aspergillus nidulans	0.25	≤0.25			>0.25
Aspergillus niger	4	—			—
Aspergillus terreus	1	≤1			>1

Dosing

• Isavuconazole 200 mg IV tid for 6 doses followed by 200 mg IV daily

Renal Dosing

• No adjustment needed

Hepatic Dosing

• No adjustment needed

Safety

Adverse Drug Reactions

• Nausea, vomiting, diarrhea
• Elevated liver enzymes
  • Generally transient ALT elevation that does not require change in therapy
  • May also include severe cholestatic or hepatocellular enzyme rises within the first few months of therapy
  • See also LiverTox
• Hypokalemia

Drug-Drug Interactions

• Increases levels of sirolimus and tacrolimus
• Increases levels of cyclosporine
• Contraindicated with carbamazepine