Posaconazole

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Anti infectives for systemic use -> Antibacterials for systemic use

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antifungal Agents; Trypanocidal Agents; 14-alpha Demethylase Inhibitors

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

EMA approved medicines: Human medicine

FDA approved drugs -> Active ingredient

Active Ingredients (posaconazole) -> FDA Greenbook

Pharmaceuticals -> UK Veterinary Medicines Directorate List

This chemical does not meet GHS hazard criteria for 2% (1 of 50) of reports.

Danger

H319 (74%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

P203, P260, P264, P264+P265, P270, P273, P280, P305+P351+P338, P318, P319, P337+P317, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 50 reports by companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Warning

Eye Irrit. 2 (74%)

Reproductive toxicity - category 2

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Drug interactions mediated by various CYP450 are common with the currently available triazole antifungals, however ... posaconazole may have an improved and more narrow drug interaction profile (CYP3A4 only) compared with other triazoles.

This study evaluated the potential for a pH-dependent pharmacokinetic interaction between posaconazole and an antacid (Mylanta), under fasting and nonfasting conditions. Twelve men completed this randomized, four-period crossover, single-dose study. Subjects received 200 mg of posaconazole following a 10-h fast, with 20 ml of Mylanta and a 10-h fast, with 20 ml of Mylanta and a high-fat breakfast, and with a high-fat breakfast alone. Antacid coadministration had no statistically significant effects on posaconazole bioavailability under fasting or nonfasting conditions. In the fasting state, antacid slightly increased the relative oral bioavailability of posaconazole by 15% (P = 0.296); in the nonfasting state, antacid decreased the relative bioavailability of posaconazole by 12% (P = 0.352). Food increased the relative oral bioavailability of posaconazole by 400% (P = 0.001). In conclusion, the effect of antacid on posaconazole exposure in the fasting or nonfasting state was small and is not considered clinically significant.

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Posaconazole is an antifungal agent structurally related to itraconazole. It is a drug derived from itraconzaole through the replacement of the chlorine substituents with flourine in the phenyl ring, as well as hydroxylation of the triazolone side chain. These modifications enhance the potency and spectrum of activity of the drug. Posaconazole can be either fungicial or fungistatic in action.

As a triazole antifungal agent, posaconazole exerts its antifungal activity through blockage of the cytochrome P-450 dependent enzyme, sterol 14α-demethylase, in fungi by binding to the heme cofactor located on the enzyme. This leads to the inhibition of the synthesis of ergosterol, a key component of the fungal cell membrane, and accumulation of methylated sterol precursors. This results in inhibition of fungal cell growth and ultimately, cell death.

Posaconazole is a novel lipophilic antifungal triazole that inhibits cytochrome P450-dependent 14-alpha demethylase in the biosynthetic pathway of ergosterol. Inhibition of this enzyme leads to an accumulation of toxic 14-alpha methylsterols and a depletion of ergosterol, resulting in a perturbation of the function of the fungal cell membrane and blockage of cell growth and division. ...

... The primary mechanism of action of the drug was inhibition of the parasite's sterol C-14 alpha demethylase.

The in vitro activity of the novel triazole antifungal agent posaconazole was assessed in 45 laboratories against approximately 19,000 clinically important strains of yeasts and molds. The activity of posaconazole was compared with those of itraconazole, fluconazole, voriconazole, and amphotericin B against subsets of the isolates. Strains were tested utilizing Clinical and Laboratory Standards Institute broth microdilution methods using RPMI 1640 medium (except for amphotericin B, which was frequently tested in antibiotic medium 3). MICs were determined at the recommended endpoints and time intervals. Against all fungi in the database (22,850 MICs), the MIC(50) and MIC(90) values for posaconazole were 0.063 microg/ml and 1 mug/ml, respectively. MIC(90) values against all yeasts (18,351 MICs) and molds (4,499 MICs) were both 1 mug/ml. In comparative studies against subsets of the isolates, posaconazole was more active than, or within 1 dilution of, the comparator drugs itraconazole, fluconazole, voriconazole, and amphotericin B against approximately 7,000 isolates of Candida and Cryptococcus spp. Against all molds (1,702 MICs, including 1,423 MICs for Aspergillus isolates), posaconazole was more active than or equal to the comparator drugs in almost every category. Posaconazole was active against isolates of Candida and Aspergillus spp. that exhibit resistance to fluconazole, voriconazole, and amphotericin B and was much more active than the other triazoles against zygomycetes. Posaconazole exhibited potent antifungal activity against a wide variety of clinically important fungal pathogens and was frequently more active than other azoles and amphotericin B.