Pharmacologic and clinical evaluation of posaconazole

Abstract

Posaconazole, a broad-spectrum triazole antifungal agent, is approved for the prevention of invasive aspergillosis and candidiasis in addition to the treatment of oropharyngeal candidiasis. There is evidence of efficacy in the treatment and prevention of rarer, more difficult-to-treat fungal infections. Posaconazole oral suspension solution has shown limitations with respect to fasting state absorption, elevated gastrointestinal pH and increased motility. The newly approved delayed-release oral tablet and intravenous solution formulations provide an attractive treatment option by reducing interpatient variability and providing flexibility in critically ill patients. On the basis of clinical experience and further clinical studies, posaconazole was found to be a valuable pharmaceutical agent for the treatment of life-threatening fungal infections. This review will examine the development history of posaconazole and highlight the most recent advances.

Keywords:

• antifungal
• immunosuppression
• invasive fungal infection
• pharmacokinetics
• pharmacology
• posaconazole
• triazole

Financial & competing interests disclosure

J Moore and J Healy were supported by National Institutes of Health Postdoctoral training grant no. T32GM008562. W Kraft’s employer has received research grant support from Merck for clinical trials in which W Kraft was the Principal Investigator. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality for immunocompromised patients; unfortunately, the clinical usefulness of many antifungal agents is limited by safety and tolerability.

• Posaconazole is a relatively safe and well-tolerated broad-spectrum azole antifungal agent.

• Newer posaconazole formulations, oral tablet and intravenous, increase its availability to a larger patient population.

• Posaconazole is a cost–effective and dominant option compared with standard antifungal therapy in many markets.

• Posaconazole continues to be studied for additional fungal infections beyond original approval, including toenail onychomycosis, Chagas disease and chronic granulomatous disease.

Notes