Posaconazole: An Update of Its Clinical Use

Abstract

Posaconazole (PCZ) is a relatively new addition to the azole antifungals. It has fungicidal activities against Aspergillus fumigatus, Blastomyces dermatitidis, selected Candida species, Crytopcoccus neoformans, and Trichosporon. PCZ also has fungistatic activities against Candida, Coccidioides, selected Fusarium spp., Histoplasma, Scedosporium and Zygomycetes. In addition, combining the drug with caspofungin or amphotericin B results in a synergistic interaction against A. fumigatus, C. glabrata and C. neoformans. The absorption of PCZ suspension is enhanced when given with food, nutritional supplements, and carbonated beverages. Oral administration of PCZ in divided doses also increases its bioavailability. PCZ has a large volume of distribution and is highly protein bound (>95%). The main elimination route of PCZ is fecal. PCZ is an inhibitor of the CYP3A4 enzyme; therefore, monitoring for drug-drug interactions is warranted with other CYP3A4 substrates/inhibitors/inducers. The most common adverse effects include headache, fatigue, nausea, vomiting and elevated hepatic enzymes. PCZ, with its unique antifungal activities, expands the azole class of antifungal agents. Because of its limit in formulation, PCZ oral suspension is recommended in immunocompromised patients with functional gastrointestinaltracts who fail conventional antifungal therapies or who are suspected to have a breakthrough fungal infection. However, a delayed-release tablet formulation and intravenous (IV) injection became available in 2014, expanding the use of PCZ in other patient populations, including individuals who are unable to take oral formulations.

Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study

“…Therefore, inhibitors or inducers of this elimination pathway may affect the serum concentration of PCZ (Dolton et al, 2012). With unchanged administration of phenytoin (to prevent seizures), on the 10th day of a steadystate serum concentration, the PCZ level was reduced by as much as 50%, which corresponds to a 90% increase in the steadystate PCZ clearance rate (Leung et al, 2015). At present, routine measurements of the serum concentration of PCZ is not carried out in clinical practice in China.…”

Sample Preparation of Posaconazole Oral Suspensions for Identification of the Crystal Form of the Active Pharmaceutical Ingredient

“…For this purpose, Posaconazole oral suspensions were used. Posaconazole is a broad-spectrum member of the second generation antifungal triazole drugs and is used against invasive fungal infections [ 8 , 9 ]. It is commercially available as an oral suspension (40 mg/mL), as a concentrate for solution for intravenous infusion (300 mg) and as gastro-resistant tablets (100 mg) [ 10 ].…”

Emerging Antifungal Targets and Strategies

“…The drug absorption is enhanced when posaconazole is given with food, nutritional supplements, and carbonated beverages, while the oral administration in divided doses raises its bioavailability. The most frequently reported side effects are headache, fatigue, nausea, vomiting, and elevated hepatic enzymes [33]. Fluconazole is by chemical structure bistriazole, a derivative of 1,2,4-triazole (Figure 5).…”

“…This compound blocks the yeast-to-hypha transition and reduces the cellular surface hydrophobicity of the biofilm cells [75]. Ctn [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34], the C-terminal fragment of crotalicidin, an antimicrobial peptide from the rattlesnake Crotalus durissus terrificus venom, displayed antifungal activity towards C. albicans. Both referent and fluconazole resistant C. albicans, in planktonic or biofilm form of growth, were susceptible to the peptide application.…”