Posaconazole is a potent, extended-spectrum, investigational
triazole anti-fungal that is highly active in pre-clinical in vitro and in vivo models against a wide array of yeasts and moulds, including Aspergillus, Fusarium and Zygomycetes, which are often refractory to
polyenes and older
azoles. In humans, orally administered
posaconazole is absorbed under fed or fasted conditions; however, absorption is significantly improved when it is coadministered with food or liquid nutritional supplements and when the daily dose is divided (into two or four daily doses). Unlike newer
azoles,
posaconazole is not extensively metabolised by
cytochrome P450 (CYP)
enzymes and is primarily excreted as parent compound in the faeces.
Posaconazole is a
CYP3A4 inhibitor, but it does not inhibit the activity of other CYP
enzymes. Therefore, in comparison with other
azole anti-fungal drugs,
posaconazole may have the potential for fewer drug interactions. The pharmacokinetics of
posaconazole are not influenced by age, gender or race. Dose adjustments for renal or hepatic impairment do not appear to be indicated based on results from single-dose studies. Preliminary efficacy data from clinical trials are promising. As
salvage therapy,
posaconazole elicited complete or partial responses in 44 to 75% of patients (N = 97) with
invasive fungal infections who were intolerant of, or who had disease refractory to,
amphotericin B or
itraconazole. In an analysis of patients with
aspergillosis, a 42% success rate was observed in the
posaconazole arm (n = 107) compared with a 26% success rate in the control arm (n = 86). Importantly, Kaplan-Meier analysis demonstrated a survival benefit in
posaconazole-treated patients. Moreover,
posaconazole yielded complete or partial responses in 71% of patients with
zygomycosis (N = 24).
Posaconazole appears to be well tolerated over long-term administration (>1 year) and may represent an important addition to the anti-fungal armamentarium.