Table 2.

Antifungal agents used to prevent and treat aspergillosis

Antifungal drug	Dosing	Comments
Voriconazole	Adults: Intravenous (IV) 6 mg/kg Q12h × 2 doses, then 4 mg/kg Q12h; Oral 200 mg or rounded to 4 mg/kg twice daily	■Superior to amphotercin B as primary therapy for invasive aspergillosis ■Toxicities: reversible visual symptoms are common, but rarely require stopping drug; liver enzyme abnormalities, encephalopathy (uncommon) ■Drug-drug interactions similar to other mould-active azoles ■Significant inter-individual variability in systemic exposure; therapeutic drug monitoring can be considered ■CYP 2C19 has genetic polymorphisms, with 15–20% of Asians expected to be slow metabolizers ■IV formulation should be used with caution in patients with significant renal impairment (e.g., creatinine clearance < 50 ml/min) because of potential for systemic accumulation of the cyclodextrin vehicle that can, in turn, cause renal toxicity.
	Pediatric: 7 mg/kg twice daily without a loading dose is approved by the European Medicines Agency (EMEA) in children aged 2 to 11 years; older children should be dosed as adults
Itraconazole	- Oral capsules: 400 mg daily, which can be administered QD or divided b.i.d..	■Oral solution has better bioavailability compared to the capsule ■Therapeutic drug monitoring is advised, aiming for a trough of at least 250 ng/ml by HPLC ■Contraindicated in patients with systolic cardiac dysfunction of a history of congestive heart failure ■Effective in corticosteroid-dependent ABPA ■IV formulation should be used with caution in patients with significant renal impairment because of potential for systemic accumulation of the cyclodextrin vehicle that can, in turn, cause renal toxicity.
	-Oral solution: 2.5 mg/kg b.i.d.
	- Pediatric oral dosing for children aged > 5 years: 2.5 mg/kg b.i.d; experience in younger children is lacking
	- Intravenous (no longer marketed in U.S.) : 200 mg b.i.d. × 4 doses, then 200 mg daily
Posaconazole	U.S. FDA-approved prophylactic dose: 200 mg T.I.D. in patients aged 13 years and over at high risk for invasive fungal disease	■Currently, only available as an oral formulation ■Variable serum levels ■Must be taken with food or enteral nutrition; oral bioavailability is maximized when taken with fatty food ■Effective as prophylaxis in patients with acute myelogenous leukemia and myelodysplastic syndrome receiving induction chemotherapy [65] and in patients with severe GVHD [66].
Amphotericin B deoxycholate	Invasive mould diseases: 1.0 to 1.5 mg/kg daily	■Significant infusional and nephrotoxicity can limit its use ■Saline hydration may avert nephrotoxicity ■Lipid formulations are generally better tolerated
Liposomal amphotericin B	Adults: 3 mg/kg daily	■3 mg/kg/day as effective as but less toxic than 10 mg/kg/day as initial therapy for invasive aspergillosis in adults [68]
	Clearance and volume of distribution influenced by body weight in pediatric oncology patients; higher mg/kg dosing may be optimal in patients weighing less than 20 kg [67]
Amphotericin B lipid complex	5 mg/kg daily	■large non-randomized database for invasive aspergillosis [69]
Amphotericin B colloidal dispersion (ABCD)	5–6 mg/kg/day	■ABCD (6 mg/kg/day) resulted in similar efficacy, lower nephrotoxicity, and greater infusional toxicity compared to Amb-D (1–1.5 mg/kg/day) as primary therapy for invasive aspergillosis [70]
Caspofungin	- FDA-approved dose: 70 mg × 1, then 50 mg daily; dose of 70 mg daily can be considered for invasive aspergillosis [71]	■Only echinocandin FDA-approved as salvage therapy for invasive aspergillosis
	- In patients with moderate hepatic insufficiency (Child-Pugh score 7 to 9), a dose of 70 mg × 1, followed by 35 mg daily is advised by U.S. FDA.
	- Pediatric dose: 50 mg/m2 (35 mg/m2 in patients with moderate liver disease) [72]
Micafungin	- Prophylaxis in adult HSCT recipients during neutropenia: 50 mg daily; no approved dose as therapy for aspergillosis	■Non-randomized trial showed safety of micafungin alone and in combination in patients with invasive aspergillosis [73]
Anidulafungin	- no approved dose as therapy for aspergillosis	■No clinical trial data as therapy for invasive aspergillosis ■randomized trial underway comparing voriconazole + anidulafungin with voriconazole alone as primary therapy for invasive aspergillosis