Pharmacy & Therapeutics- July 2008 - (Page 394) DRUG FORECAST Candidiasis Vazquez et al., 200615 Oropharyngeal candidiasis is a common opportunistic infection in patients with HIV infection. In a multicenter, randomized, single-blinded study, the efficacy of posaconazole versus fluconazole was compared in subjects with HIV and orophar yngeal candidiasis. The posaconazole dose was 200 mg daily, and the fluconazole dose was 100 mg daily for 13 days. Clinical success, including cure or improvement on day 14, was assessed in 329 subjects. The durability of clinical success was evaluated on day 42. Clinical success was noted in 91.7% of posaconazole patients and in 92.5% of fluconazole subjects (95% CI, –6.61% to 5.04%), indicating the non-inferiority of posaconazole. After 14 days of therapy, mycological success was described in 68% of patients in both groups, and by day 42, significantly more posaconazole recipients than fluconazole recipients experienced continuous mycological success (40.6% vs. 26.4%) (P = 0.038). Skiest et al., 200716 open-label, multicenter study of patients with invasive aspergillosis and other mycoses who did not respond to or who were intolerant of conventional antifungal therapy. The controls constituted a retrospectively retrieved reference group of patients who had been treated with other antifungals. The data were reviewed by committee-assessed global responses generated by 15 experts in antifungal therapy and by two radiologists who evaluated posaconazole-treated subjects and controls in a parallel, blinded fashion using predefined methods to determine evaluability and outcomes. Overall, 107 posaconazole-treated subjects and 86 controls were enrolled. Demographics and disease assessments were similar between the groups. At the end of treatment, the success rates were 42% for the posaconazole recipients and 26% for the control subjects, with an odds ratio of 4.06 (95% CI, 1.50–11.04) (P = 0.006). duration of 34 to 365 days, 73% of the patients achieved therapeutic success. Other Fungal Infections Histoplasma capsulatum is an endemic dimorphic fungus commonly found in the midwestern U.S. It is difficult to treat because of granulomatous tissue lesions and the requirement for long-term therapy. Several case repor ts and series describe successful eradication of H. capsulatum with posaconazole.21,22 In immunocompetent patients who were previously unresponsive to itraconazole therapy, posaconazole was effective in treating this infection.21 Another case series of six patients described success with posaconazole in patients who had been unresponsive to other antifungal regimens.22 Fusarium, a filamentous fungus and an opportunistic pathogen, is generally resistant to most antifungal agents. One case report described Fusarium proliferatum infection in a patient with chronic rejection after lung transplantation who had received posaconazole and improved after four months of treatment.23 In a case series that included three patients with refractory disease, Fusarium keratitis was successfully treated with posaconazole.24 Other rare superficial and subcutaneous mycotic infections (e.g., chromoblastomycosis, hyalohyphomycosis, or phaeohyphomycosis) have been successfully treated with posaconazole.25 Zygomycosis Greenberg et al., 200618 The efficacy and safety of posaconazole in oropharyngeal and esophageal candidiasis were evaluated in patients with HIV infection who had been clinically unresponsive to fluconazole or itraconazole. The subjects were given one of two different regimens of posaconazole: • 400 mg twice daily for three days, followed by 400 mg once daily for 25 days (regimen 1) • 400 mg twice daily for 28 days (regimen 2) Clinical response was detected in 75% of both treatment groups. Response rates were similar between regimen 1 (75.3%) and regimen 2 (74.7%). Of those subjects with disease resistant to fluconazole, 73% responded and 74% of those with infection resistant to itraconazole achieved clinical cure. Overall, 74% of all subjects with resistant isolates were cured with posaconazole. Of those patients with esophageal candidiasis, 74.4% responded to posaconazole. The investigators reported the results from the first 24 patients with active zygomycosis who were enrolled in compassionate trials evaluating oral posaconazole as salvage therapy for IFIs. Of the 24 patients exposed to posaconazole, 79% survived the infection. Survival was also linked to surgical resection as well as stabilization and improvement of the patients’ underlying illnesses. Coccidioidomycosis Catanzaro et al., 200719 SAFETY PROFILE Raad and associates collected the overall long-term safety data of posaconazole in 428 patients with IFIs and 66 patients with FN. 26 Overall, treatment-related adverse effects were reported in 38% of patients. The most common adverse drug effects reported were nausea (8%) and vomiting (6%). Treatment-related prolongation of the corrected QT interval (QTc) occurred in 1% of patients, and 2% of patients had elevated hepatic enzymes. Overall, the long-term safety of posaconazole of six months or longer revealed a favorable adverse-effect profile in seriously ill immunocompromised patients. In clinical reports, the tolerability of posaconazole was acceptable and comparable to other triazoles.12–26 Common adverse events included fever, nausea, vomiting, diarrhea, abdominal pain, dry The safety and tolerability of posaconazole were reviewed in 20 patients with chronic pulmonary or nonmeningeal disseminated coccidioidomycosis. The efficacy of posaconazole was also evaluated as a secondar y endpoint in this trial. Overall, 70% of patients completed the study and showed a positive response. Stevens et al., 200720 Aspergillosis Walsh et al., 200717 The efficacy and safety of posaconazole monotherapy were evaluated in an The efficacy of posaconazole was evaluated in 15 patients with chronic refractor y coccidioidomycosis. The sites of infection were pulmonary in origin in seven patients and of disseminated origin in eight patients. The participants in this analysis had infection that had been refractory to previous therapy, including amphotericin B with or without a triazole. After treatment with posaconazole for a 394 P&T® • July 2008 • Vol. 33 No. 7
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