Antifungal agent against a wide range of yeasts, including candida species and molds including aspergillus species, Zygomycetes and Fusarium species.
Trade name is Noxafil.
An oral triazole antifungal drug.
Metabolism is by hepatic glucuronidation.
Absorbed within three to five hours.
It is predominately eliminated through the liver, and has a half life of about 35 hours.
Drug half-life is 16 to 31 hours.
Fecal excretion is 77% and renal 14%.
Oral administration with a high-fat meal exceeds 90% bioavailability and increases the concentration by four times compared to fasting state.
Posaconazole is available only as a suspension for oral use.
Absorption is increased when taken with food, especially fatty meals, and is not affected by use of antacids.
Oral absorption is better in divided daily doses and optimal when administered four times daily.
Absorption is saturated for doses more than 800 mg daily.
Absorption is diminished in patients undergoing allogeneic bone marrow transplantation.
It is more than 98% protein bound, and its volume of distribution is compatible with good tissue penetration.
It is metabolized in the liver through glucuronidation and excreted primarily in bile (76.9%) and in urine (14%) as unchanged drug or inactive metabolites.
It is not metabolized through liver CYP450 system enzymes, but it is a moderate inhibitor of CYP3A4, which leads to increased blood levels of drugs using the CYP3A4 metabolic pathway when coadministered.
There is no need for dose adjustment in patients with moderate to severe renal disease.
Not been adequately studied in patients with hepatic insufficiency.
Triazoles have numerous clinically significant drug interactions, most of these interactions arise from competitive inhibition of liver oxidative metabolism via rapid reversible binding to CYP450 system enzymes.
Mechanism of action is by disrupting the close packing of acyl chains of phospholipids, impairing the functions of certain membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system.
It inhibits growth of the fungi by blocking the synthesis of ergosterol by inhibiting of the enzyme lanosterol 14α-demethylase and accumulation of methylated sterol precursors.
It is significantly more potent at inhibiting 14-alpha demethylase than itraconazole.
Active against Candida spp., Aspergillus spp, and Zygomycetes spp.
It is used to treat invasive infections by Candida species, Mucor, and Aspergillus species in severely immunocompromised patients.
May be superior to other triazoles, such as fluconazole or itraconazole, in the prevention of invasive fungal infections, although it may cause more serious side effects.
Has potent in vitro activity against most Candida and Aspergillus species.
Posaconazole is also approved for the treatment of patients with oropharyngeal candidiasis, including those refractory to fluconazole and itraconazole.
Studies demonstrated a promising response rate in this setting for zygomycosis, histoplasmosis, fusariosis, coccidioidomycosis, or patients with chronic granulomatous disease.
Active against Scedosporium spp., Fusarium spp., Histoplasma spp., Coccidioides spp., Penicillium marneffei, Sporothrix schenckii, Blastomyces dermatitidis, Trichosporon spp., and Cryptococcus neoformans as well as several dematiaceous molds.
Approved for prophylaxis against fungal infections in severely immunocompromised patients, such as hematopoietic stem cell transplant patients (HSCT), who are at least 13 years of age, with graft versus host disease (GVHD) and patients with hematologic malignancies and neutropenia due to chemotherapy.
Its most distinctive characteristic, though, when compared with other azoles, is the improved activity posaconazole exhibits against the zygomycetes.
The safety profile of posaconazole seems to be more favorable than that of azoles.
Well tolerated.
Common adverse events are headaches and gastrointestinal complaints, such as nausea, diarrhea, and vomiting.
Hepatotoxicity and liver enzyme abnormalities have been reported in less than 2 to 3% of patients,hypokalemia in 3%, and rash in 3%.
Q-Tc prolongation was reported to be as high as 4% in one study.
Long-term treatment seems to be equally safe.
Because skeletal malformations have been reported in treated rats, use in pregnancy should be avoided (class C drug).
May be the most effective treatment for both chronic and acute Chagas disease.
Indicated for prophylaxis of invasive Aspergillus and Candida infections in patients 13 years and older, who are at high risk of developing these infections because of severe immunosuppression from stem cell transplantation or have prolonged chemotherapy induced myelosuppression.