Posaconazole in the management of refractory invasive fungal infections

Figures & data

Table 1 Drug profiles.

Antifungal class	Polyene		Azoles				Echinocandins		Fluoropyrimidines
	Amphotericin B	Lipid formulations	Fluconazole	Itraconazole	Voriconazole	Posaconazole	Caspofungin	Anidulafungin	Flucytosine
Formulation	intravenous	intravenous	intravenous/oral	intravenous/oral	intravenous/oral	oral	intravenous	intravenous	oral
Mechanism of action	Interaction with ergosterol, intercalation of fungal membrane, increased membrane permeability		Inhibition of cytochrome P450 14 alpha-demethylase, accumulation of lanosterol leading to perturbation of fungal cell membrane, fungistasis				Inhibition of cell-wall glucan synthesis leading to susceptibility of fungal cell to osmotic lysis		Interferance with DNA/RNA synthesis
Loading dose/day	No	No	No	400 mg iv /4 days 600 mg po /3 days	12 mg/kg iv	No	70 mg	200 mg	No
Usual maintenance dose/day	0.6–1.5 mg/kg	3–6 mg/kg	400–800 mg iv/po	200 mg iv 400–600 mg po	8 mg/kg iv 400 mg po	600–800 mg	50 mg	100 mg	100 mg/kg
Fequency of dosing	daily	daily	daily	twice daily	twice daily	2–4 divided doses	daily	daily	every 6 hours
Half-life (hours)	24	100–153	30	56–64	dose dependent	20	9–11	52	2.5–6
Oral bioavailability	NA	NA	>90%	55%	96%	variable*	NA	NA	75%–90%
CNS penetration	poor	data not available	very good	moderate	excellent	moderate	poor	poor	very good
Route of elimination	slow renal excretion	data not available	renal	fecal (primarily) renal	fecal	fecal (primarily) renal	fecal renal	fecal	renal
Dose reduction in renal failure	consider lipid formulation	not required	required	not required	not required	not required	not required	not required	required
Dose reduction in hepatic failure	data not available	data not available	not required	data not available	not recommended in severe cirrhosis	data not available	recommended for high Child-Pugh scores	not required	data not available
Major toxic effects	dose-limiting renal toxicity, fever, chills	less toxic than amphotericin B	well tolerated occasional GI intolerance	liver and GI toxicity	drug inter-actions, visual, liver, skin toxicity	well tolerated occasional GI and liver intolerance	well tolerated occasional histamine mediated symptoms	well tolerated occasional fever, diarrhea	GI intolerance marrow suppression

Abbreviations: NA, not applicable; iv, intravenous; po, orally; CNS, central nervous system; GI, gastrointestinal.

* enhanced with food (2-fold), with high fat meal (4-fold)