Profile of isavuconazole and its potential in the treatment of severe invasive fungal infections

Figures & data

Figure 1 Chemical structure of the prodrug, active drug, and cleavage product of isavuconazole.

Table 1 Pharmacokinetic and pharmacodynamic properties of isavuconazole compared with other azole antifungals^{10,12,48–52}

Characteristic	Antifungal drug
	Isavuconazole	Voriconazole	Itraconazole	Posaconazole	Fluconazole
Available formulations	Oral and IV	Oral and IV	Oral*	Oral	Oral and IV
Bioavailability	Very high	Up to 95%	30% capsules 50% solution	Not applicable	95%
Protein binding	98%	58%	>99%	99%	10%
Food effect	No effect	Negative effect	Positive effect for capsules Negative effect for solution	Positive effect	Negative effect
Volume of distribution (L/kg)	High (4.4–7.7)	High (4.6)	Very high (10.7)	High (6.5)	Low (0.7)
CNS penetration	Low in CSF, high in brain	High (>50%)	Low (<10%)	Low	High (>60%)
Clearance (L/h)	Low (1.9–2.8)	High (8.4)	Very high (15.9)	Very high (21.7)	Low (1.2)
Half-life (h)	56–104	6–12	24–30	16–35	24–30
Probability of drug interactions	Moderate	High	High	Moderate	Moderate
Use in hepatic insufficiency	Reduce dose; avoid in severe hepatic disease	Reduce dose; avoid in severe hepatic disease	Reduce dose; avoid in severe hepatic disease	No dose adjustment; monitor carefully; avoid in severe hepatic disease	Reduce dose; avoid in severe hepatic disease

Note:

* The IV formulation of itraconazole is no longer widely available in the international market.

Abbreviations: CNS, central nervous system; CSF, cerebrospinal fluid; IV, intravenous; L/h, liter/hour; h, hour.

Table 2 Minimum inhibitory concentrations for isavuconazole, for 50% and 90% (MIC₅₀ and MIC₉₀, respectively) of Candida spp. isolates.¹⁸

Pathogen	Antifungal agent	MIC50 (μg/mL)	MIC90 (μg/mL)
Candida albicans	Isavuconazole	<0.002–0.03	<0.002–0.03
	Voriconazole	<0.016–0.03	0.03–0.06
	Caspofungin	0.03–0.5	0.03–1
	Amphotericin B	0.25–0.5	0.5–1
Candida glabrata	Isavuconazole	0.25–2	0.5–8
	Voriconazole	0.125–1	1–4
	Caspofungin	0.125	0.125–0.25
	Amphotericin B	0.5–2	0.5–2
Candida krusei	Isavuconazole	0.125–0.5	0.25–1
	Voriconazole	0.25–0.5	1–4
	Caspofungin	0.25	0.25–0.5
	Amphotericin B	0.5–2	0.5–4
Candida parapsilosis	Isavuconazole	<0.015–0.03	0.03–0.125
	Voriconazole	<0.015–0.6	0.06–0.125
	Caspofungin	0.25	1–2
	Amphotericin B	0.25–1	0.5–2
Candida tropicalis	Isavuconazole	<0.015–0.03	0.03–0.125
	Voriconazole	0.03–0.125	0.06–2
	Caspofungin	0.125–0.25	0.5
	Amphotericin B	0.5–2	0.5–2

Note: Copyright © 2010, Springer Science and Business Media. Adapted with permission from Thompson GR III, Wiederhold NP. Isavuconazole: a comprehensive review of spectrum of activity of a new triazole. Mycopathologia. 2010;170(5):291–313.¹⁸

Abbreviation: MIC, minimum inhibitory concentration.

Table 3 Minimum inhibitory concentrations of isavuconazole and selected antifungal agents for 50% and 90% (MIC₅₀ and MIC₉₀, respectively) of Aspergillus spp. isolates.¹⁸

Pathogen	Antifungal agent	MIC50 (μg/mL)	MIC90 (μg/mL)
Aspergillus fumigatus	Isavuconazole	0.25–1	0.5–2
	Voriconazole	0.25–1	0.5–2
	Caspofungin	0.06–0.5	0.06–0.5
	Amphotericin B	0.25–4	0.5–8
Aspergillus terreus	Isavuconazole	0.5–1	0.5–4
	Voriconazole	0.25–1	0.5–2
	Caspofungin	0.03–0.5	0.06–0.5
	Amphotericin B	1–4	1–8
Aspergillus flavus	Isavuconazole	0.5–2	1–16
	Voriconazole	0.5–1	0.5–2
	Caspofungin	0.03–0.25	0.03–0.25
	Amphotericin B	1–2	1–4
Aspergillus niger	Isavuconazole	0.5–2	2–4
	Voriconazole	0.25–2	1–2
	Caspofungin	0.06–0.25	0.125–0.25
	Amphotericin B	0.5–1	0.5–2

Note: Copyright © 2010, Springer Science and Business Media. Adapted with permission from Thompson GR III, Wiederhold NP. Isavuconazole: a comprehensive review of spectrum of activity of a new triazole. Mycopathologia. 2010;170(5):291–313.¹⁸

Abbreviation: MIC, minimum inhibitory concentration.

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