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.

Figure 1

Chemical structures of common triazole anti-fungal drugs and isavuconazonium.

Figure 2

Key patient populations with posaconazole drug interactions. Adapted from references [7,16,19,22,42].

Figure 3. Regulatory history of posaconazole

Adapted from references [,,–65]. DRT: Delayed release tablet; EMA: European medicines agency; FDA: Food and drug administration; IFI: Invasive fungal infections; IV: Intravenous; OPC: Oropharyngeal candidiasis; PREA: Pediatric Research Equity Act.

Figure 4. Posaconazole therapy algorithm

Unless otherwise noted, listed dosages are for the posaconazole oral suspension. All other indications shown are off-label uses. Adapted from references [5,16,78,79]. ^†Denotes FDA approval for the posaconazole oral suspension. ^‡Denotes FDA approval for all available posaconazole formulations. b.i.d.: Twice daily; DRT: Delayed-release tablet; iv.: Intravenous solution; q.d.: Once daily; q.i.d.: Four-times a day; SUS: Suspension; t.i.d.: Thrice daily.