title: Continuous infusion of escalated doses of amphotericin B deoxycholate: an open-label observational study.
abstract: Amphotericin B deoxycholate (AmB-d) remains a mainstay of antifungal therapy for immunocompromised patients, despite being associated with significant therapy-related toxicity. Because continuous infusion of AmB-d is better tolerated than traditional administration over 2-6 hours, we evaluated escalation of the AmB-d dose in 33 patients (31 of whom were neutropenic), for whom the initial dosage of AmB-d (1 mg/kg/day) was gradually increased to 2.0 mg/kg/day when renal function remained stable and the drug was tolerated. Dose escalation was possible without delay in 28 patients. Median duration of AmB-d therapy was 16 days (range, 7-72 days). Infusion-related reactions accompanied <18% of AmB-d infusions. Twenty-seven patients had a decrease in creatinine clearance while receiving AmB-d therapy. A >2-fold decrease in creatine clearance was observed in 5 patients, and the decrease was dose-limiting in only 1 patient; no dialysis was required. In conclusion, continuous infusion of AmB-d escalated to 2.0 mg/kg/day seems not to cause additional impairment of vital organ functions and to be well tolerated by most patients.
authors.affiliation: Department of Internal Medicine, Medical Clinic B, University Hospital, Zürich, Switzerland. aimhof@fhcrc.org
authors.forename: Alexander
authors.initials: A
authors.lastname: Imhof
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
authors.forename: Andreas
authors.initials: A
authors.lastname: Schaffner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007260:Infusion Pumps / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy*; D009325:Nausea / Q000209:etiology; D009503:Neutropenia / Q000209:etiology; D009894:Opportunistic Infections / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination