Open-label, randomized comparison of itraconazole versus caspofungin for prophylaxis in patients with hematologic malignancies.

Invasive fungal infection remains the most common cause of infectious death in acute leukemia. In this open-label, randomized study, we compared the efficacy and safety of caspofungin with that of intravenous itraconazole for antifungal prophylaxis in patients undergoing induction chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome. Of 200 patients, 192 were evaluable for efficacy (86 for itraconazole, 106 for caspofungin). Duration of prophylaxis (median, 21 days [range, 1 to 38 days]), demographics, and prognostic factors were similar in both groups. Ninety-nine patients completed antifungal prophylaxis without developing fungal infection (44 [51%] with itraconazole, 55 [52%] with caspofungin). Twelve patients developed documented invasive fungal infections, five in the itraconazole group (four with candidemia and one with Aspergillus pneumonia), and seven in the caspofungin group (two with candidemia, two with disseminated trichosporon species, two with Aspergillus pneumonia, and one with disseminated Fusarium spp). Two patients in the itraconazole group and four in the caspofungin group died of fungal infection (P = 0.57). Grade 3 to 4 adverse event rates were comparable between groups; the most common event in both was reversible hyperbilirubinemia. No evidence of cardiovascular toxicity from intravenous itraconazole was noted among patients older than 60. In conclusion, intravenous itraconazole and caspofungin provided similar protection against invasive fungal infection during induction chemotherapy, and both drugs were well tolerated.

Beneficial pharmacokinetic interaction between cyclosporine and itraconazole in renal transplant recipients.

BACKGROUND: Itraconazole is often given for fungal prophylaxis to renal transplant recipients, who require concomitant cyclosporine in the immediate posttransplant period. We determined the extent of the pharmacokinetic interaction between cyclosporine and itraconazole oral solution in renal transplant recipients and the effect on daily drug costs. METHOD: This was a single-center, open-label, nonrandomized study. Posttransplantation, renal transplant recipients received itraconazole solution 200 mg twice daily and cyclosporine, dosed to achieve target concentrations. Once at steady state, blood samples were collected over 12 hours for pharmacokinetic evaluation of cyclosporine, itraconazole, and hydroxy-itraconazole. Itraconazole was discontinued after approximately a 3-month prophylaxis regimen. Cyclosporine doses were titrated to achieve target concentrations and cyclosporine concentrations were once again determined when steady state was achieved. A noncompartmental analysis was used to analyze cyclosporine pharmacokinetic parameters. The pharmacoeconomic impact was measured based on the percent change in dose of cyclosporine when administered with and without itraconazole. Drug costs were calculated using the average wholesale price. The cost per patient, as well as the average cost, was calculated for the cyclosporine/itraconazole combination, as well as the cyclosporine regimen alone. RESULTS: Eight renal transplant recipients completed the study. All were included for itraconazole analyses and seven for cyclosporine analyses. Mean peak and trough itraconazole levels were 1.64 +/- 0.82 and 1.23 +/- 0.90 microg/mL respectively. Mean peak and trough hydroxy-itraconazole levels were 2.37 +/- 1.55 and 2.20 +/- 1.48 microg/mL, respectively. While on itraconazole, a 48% reduction in the mean total daily dose of cyclosporine was necessary to maintain target concentrations (171 +/- 63.6 versus 329 +/- 103.5 mg, P =.003). This reduction in cyclosporine dose resulted in a discounted itraconazole daily drug cost of approximately 29.5%. CONCLUSION: Administering itraconazole with cyclosporine allows for a decrease in the cyclosporine dose, thus lowering daily drug costs and providing adequate antifungal coverage with itraconazole and hydroxy-itraconazole trough concentrations above the MIC(90) of Candida and Aspergillus spp.

Recombinant human interferon-gamma in patients with chronic granulomatous disease--European follow up study.

This was an uncontrolled, open-label follow up study of a previous 12-month, randomized, double-blind, placebo-controlled trial performed to assess the long-term efficacy and safety of Recombinant Human Interferon Gamma (rIFN-gamma) in patients with chronic granulomatous disease (CGD). In two centres, 28 patients (24 male, 4 female) with a mean age of 16 years (range 3-37) entered the open-label phase. The patients were treated for a mean of 880 days (range 97-1375 days). Visits were scheduled every 180 days and patients completed one to six visits. rIFN-gamma was administered subcutaneously three times weekly at a dose of 0.05 mg per m2. During the open-label phase of the study 12 patients experienced a serious infection requiring hospitalization within 880 days. The median infection-free time was 993 days. No obvious increase of infections over time was seen. Phagocyte superoxide anion production and phagocyte staphylococcal killing were not influenced by therapy. Seven patients were withdrawn from the study, one because of an adverse reaction, three on their own wish and the other three because they changed to another trial. No patient died during the study. Conclusion. Treatment of patients with CGD with intracellular active antibiotics and additional interferon gamma as infection prophylaxis is safe and justified.