Infectious Diseases II

Adverse reactions

Increase in liver function tests

ii.

Nausea/vomiting

iii.

Drug interaction: CYP3A4 inhibitor

iv.

QTc prolongation

Isavuconazole

Spectrum of activity: Wide spectrum of activity, including Candida (similar to voriconazole),

Aspergillus (may retain activity for some species that are resistant to other azoles), Zygomycetes,

and dimorphic fungi. Limited activity against Fusarium.

Dose

Isavuconazonium: Loading dose 372 mg (equivalent to 200 mg of isavuconazole) every 8 hours

intravenously × 6 doses, maintenance dose 372 mg (equivalent to 200 mg of isavuconazole)

daily

ii.

Isavuconazonium sulfate solution is readily water soluble, unlike posaconazole and

voriconazole, and does not require stabilization with cyclodextrin.

Mainly PK advantages and safety benefits over voriconazole and posaconazole

Linear kinetics

ii.

Oral bioavailability: 98%, not affected by food or acidity

iii.

Fewer drug-drug interactions

iv.

No QTc prolongation; in fact, associated with dose-dependent QTc shortening

Mechanism of action: Inhibition of glucan synthase, which is an enzyme responsible for the formation

of 1,3-β-d-glucan. Inhibition of this enzyme leads to cessation of fungal cell wall formation.

In vitro, C. parapsilosis has a much higher MIC than other Candida spp. The clinical significance

of this is unknown. Cases of breakthrough infections with C. parapsilosis during treatment with

echinocandins have been reported. Several retrospective studies did not find worsened outcomes

associated with echinocandin treatment of C. parapsilosis. The current IDSA guidelines on

invasive candidiasis recommend using fluconazole for the treatment of C. parapsilosis.

Primarily used for invasive candidiasis, neutropenic fever, and invasive Aspergillus if patient

cannot tolerate other therapies. Recent IDSA candidiasis guidelines recommend echinocandin as

preferred initial therapy for both proven and empiric therapy.

Dose (available only as an intravenous formulation)

Caspofungin: 70 mg once, followed by 50 mg once daily

Micafungin: 100 mg once daily

Anidulafungin: 200 mg once, followed by 100 mg once daily

beginning on day 8 for up to four doses

Adverse reactions

Well tolerated with minimal GI adverse effects

Minimal drug interactions

Avoid caspofungin coadministration with cyclosporine and tacrolimus.

ii.

Avoid micafungin coadministration with nifedipine and sirolimus.

iii.

Avoid administering anidulafungin with metronidazole (disulfiram reaction).