Posaconazole is a
triazole antifungal agent with a spectrum of activity that includes Candida and Cryptococcus species, many molds, and some endemic fungi.
Posaconazole has received US Food and Drug Administration approval for the treatment of oropharyngeal
candidiasis, including
infections refractory to
itraconazole and/or
fluconazole. It is also approved as prophylaxis for invasive Aspergillus and
Candida infections in patients aged >or=13 years who are at high risk of developing these
infections, in adult and adolescent hematopoietic stem cell transplant recipients with
graft-versus-host disease, and in persons with
hematologic malignancies and prolonged
neutropenia due to
chemotherapy, who are at high risk of developing these
infections. Approval for additional indications is being sought. Limited clinical experience suggests efficacy for the treatment of
infections due to Zygomycetes and as
salvage therapy for patients with invasive
aspergillosis and
coccidioidomycosis. Currently available only as an oral
suspension,
posaconazole, which has been well tolerated, requires administration with food or a nutritional supplement to assure adequate bioavailability.
Posaconazole is predominantly eliminated in the feces, where it appears as unchanged
drug. Metabolism, mostly glucuronidation, plays only a minor role in its elimination, as does renal clearance; as a consequence, dose adjustment is not required in the presence of renal or
hepatic insufficiency. Although not a substrate of hepatic CYP450 3A4,
posaconazole inhibits this
enzyme and thus has the potential for significant pharmacokinetic interactions with drugs metabolized by this
isoform. Its use in combination with CYP450 substrates that prolong the QTc interval is contraindicated, as is its use with
ergot alkaloids; administration of
posaconazole with other substrates and/or inducers of this
enzyme system requires caution.
Posaconazole is both a substrate and inhibitor of
P-glycoprotein. Currently, the major roles for
posaconazole in clinical practice are as prophylaxis for neutropenic patients with significant risk of
infection with filamentous fungi and as
therapy for
zygomycoses. It may also have a role in the treatment of other filamentous fungal and some yeast
infections, but assessment of its overall place in antifungal
therapy awaits the availability of further clinical experience.