Itraconazole Oral Solution for Primary Prophylaxis of Fungal Infections in Patients with Hematological Malignancy and Profound Neutropenia: a Randomized, Double-Blind, Double-Placebo, Multicenter Trial Comparing Itraconazole and Amphotericin B

Abstract

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 ؋ 10 9 neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.

Amphotericin B lipid complex as prophylaxis of invasive fungal infections in patients with acute myelogenous leukemia and myelodysplastic syndrome undergoing induction chemotherapy

“…Nonetheless, these fungal infection-related mortality rates are comparable to those reported from other clinical studies evaluating fluconazole and itraconazole (fluconazole, 1.2-3.0%; itraconazole, Ͻ 1.0 -15.2%). 8,9,12,[15][16][17] In addition, no prophylaxis-related deaths occurred with either lipid-based amphotericin B product.…”

Antimicrobial prophylaxis in hematopoietic stem cell transplant recipients: heterogeneity of current clinical practice

“…The studies supporting these practices do not always reach a definitive conclusion in terms of modification of existing clinical practice. [1][2][3][4][5][6][7][8][9][10][11][12][13] Therefore, guidelines have been formulated for the prevention of infections following HSCT, 14,15 and have been endorsed by the Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation. These evidence-based reviews have made weighted recommendations for the use of antimicrobial agents as prophylaxis for bacterial, viral, and fungal pathogens.…”

Infecciones en pacientes oncohematológicos no trasplantados

“…-Itraconazol solución oral 10 . En el caso de las leucemias agudas mieloblásticas se debe emplear durante toda la fase de neutropenia cuando la neutropenia esperada sea de más de dos semanas y no haya posibilidad de aislamiento en habitaciones con aire filtrado.…”