Amphotericin B colloidal dispersion (Amphocil) vs fluconazole for the prevention of fungal infections in neutropenic patients: data of a prematurely stopped clinical trial

Bone Marrow Transplant. 2000 Apr;25(8):879-84. doi: 10.1038/sj.bmt.1702243.

Abstract

We conducted an open label, randomised clinical trial to compare amphotericin B colloidal dispersion (ABCD, Amphocil) 2 mg/kg/day intravenously with fluconazole 200 mg/day orally, for the prevention of fungal disease in neutropenic patients with haematological malignancies. In the event of unresolved fever after 4 days of empirical antibacterial therapy, patients in both treatment groups were to receive ABCD, 4 mg/kg/day. However, the study had to be stopped in an early phase, due to severe side-effects of ABCD. A total of 24 patients were enrolled, 12 patients were randomly assigned to receive prophylactic ABCD, which was administered for a mean of 13.9 days. Fluconazole prophylaxis was given to 12 patients for a mean of 21.2 days. Therapeutic ABCD, 4 mg/kg, was initiated in four patients because of suspected fungal infection, all of whom had initially received fluconazole. A high rate of infusion-related toxicity of ABCD was observed. Chills occurred in 15/16 ABCD recipients (94%), accompanied by a temperature rise of >/=2 degrees C in 4/16 patients and of >/=1 degrees C but <2 degrees C in 10/16 patients. Other ABCD-related adverse events were hypotension (4/16), nausea with vomiting (5/16), tachycardia (7/16), headache (3/16) and dyspnoea (3/16). For premedication patients received: antihistamines (12/16), hydrocortisone (9/16) and/or morphine (6/16). ABCD was discontinued in 8/16 patients (50%) due to side-effects, which ultimately dictated early termination of the study. We conclude that ABCD is not suitable for antifungal prophylaxis in neutropenic patients due to severe infusion-related side-effects. Subject numbers were too low for conclusions on variables of antifungal efficacy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amphotericin B / administration & dosage
  • Amphotericin B / toxicity*
  • Bilirubin / blood
  • Consumer Product Safety
  • Contraindications
  • Female
  • Fluconazole / administration & dosage*
  • Fluconazole / toxicity
  • Hematologic Neoplasms / complications*
  • Hematologic Neoplasms / drug therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Infusions, Intravenous / adverse effects
  • Male
  • Middle Aged
  • Morphine / therapeutic use
  • Mycoses / drug therapy*
  • Mycoses / etiology
  • Mycoses / prevention & control*
  • Neutropenia / complications*
  • Neutropenia / drug therapy
  • Respiratory Tract Diseases / chemically induced
  • Shivering
  • Survival
  • Time Factors
  • Transaminases / blood

Substances

  • Morphine
  • Amphotericin B
  • Fluconazole
  • Transaminases
  • Bilirubin