First antifungal approved for prevention of invasive fungal infections caused by Aspergillus species
Posaconazole oral suspension
SCHERING-PLOUGHFirst antifungal approved for prevention of invasive fungal infections caused by Aspergillus species
This triazole antifungal agent exerts its inhibitory effect by blocking the synthesis of ergosterol, a key component of the fungal cell membrane. Posaconazole was approved on September 18, 2006, for prophylaxis (prevention) of invasive Aspergillus and Candida infections in patients 13 years of age and older who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia from chemotherapy.
Efficacy. The efficacy of posaconazole in the prophylaxis of invasive fungal infections (IFIs) was assessed in 2 randomized, controlled studies of patients with compromised immune systems. Both studies determined efficacy of prophylaxis with a composite end point of proven/probable IFIs, death, or treatment with systemic antifungal therapy. Study 1 was a double-blind trial that compared posaconazole oral suspension (200 mg TID) with fluconazole capsules (400 mg QD) in allogeneic hematopoietic stem cell transplant (HSCT) recipients with Graft versus Host Disease (GVHD) (N=600). After a comparable duration of therapy in both treatment groups (80 days, posaconazole; 77 days, fluconazole), the rate of proven/probable IFI in the posaconazole group was 2% versus 7% in the fluconazole group. Study 2 was an open-label trial comparing posaconazole oral suspension (200 mg TID) with fluconazole suspension (400 mg once daily) or itraconazole oral solution (200 mg BID) in neutropenic patients (N=602) who were receiving cytotoxic chemotherapy for acute myelogenous leukemia or myelodysplastic syndromes. After a comparable duration of therapy in both treatment groups (29 days, posaconazole; 25 days, fluconazole/itraconazole), the rate of proven/probable IFI in the posaconazole group was 2% versus 8% in the fluconazole/itraconazole group.
Dosing. Posaconazole should be administered as a 5-mL dose given TID. Each dose of posaconazole should be administered with a full meal or with a liquid nutritional supplement in patients who can not eat a full meal. The duration of therapy should be based on recovery from neutropenia or immunosuppression.