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MICHELE I. MORRIS, M.D., is Assistant Professor of Clinical Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, 1400 N.W. 10th Avenue, D90-A, Dominion Tower, #813A, Miami, FL 33136 (mmorris2{at}med.miami.edu).

Purpose. The pharmacology, pharmacokinetics, pharmacodynamics, spectrum of activity and resistance, clinical utility, adverse effects, dosage and administration, and recommended monitoring of posaconazole are reviewed. Summary. Posaconazole is a member of the azole class of antifungals recently approved for the prophylaxis and treatment of invasive fungal infections. Posaconazole has a large volume of distribution and distributes well into tissues. Posaconazole-induced fungal killing is optimal when peak drug concentrations achieved are 2–10 times the organism’s minimum inhibitory concentration. Posaconazole demonstrates fungistatic activity against most species of Candida, Cryptococcus, and Trichosporon. In a direct comparison, posaconazole appeared 2–4 times more active than itraconazole against most pathogenic yeast species. Posaconazole also showed activity against Candida and Aspergillus isolates resistant to the other azoles and amphotericin B. Posaconazole has superior activity to the other azoles against Zygomycetes isolates. It has demonstrated activity equal or superior to other antifungal agents against almost all varieties of yeast and mold. The most common treatment-related adverse events associated with posaconazole are nausea, vomiting, diarrhea, rash, hypokalemia, thrombocytopenia, and abnormal liver function test values. Significant drug interactions include cimetidine, rifabutin, and phenytoin, for which concomitant use should be avoided, as well as cyclosporine, tacrolimus, and midazolam, for which dosage reductions are recommended. Conclusion. Posaconazole is an oral anti-fungal agent with a broader spectrum of activity and better clinical efficacy than other available antifungals. It is less nephrotoxic than the polyenes and probably less likely to be involved in drug–drug interactions than the mold-active azoles. Index terms: Antifungals; Blood levels; Dosage; Drug administration; Drug interactions; Drugs, body distribution; Minimum inhibitory concentration; Mycoses; Pharmacokinetics; Posaconazole; Resistance; Spectrum microbial; Toxicity

 

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