Comparison of 2 Doses of Liposomal Amphotericin B and Conventional Amphotericin B Deoxycholate for Treatment of AIDS‐Associated Acute Cryptococcal Meningitis: A Randomized, Double‐Blind Clinical Trial of Efficacy and Safety

Abstract

BACKGROUND. It is generally acknowledged that amphotericin B is the most effective treatment for cryptococcal meningitis. However, administration of this drug is accompanied by substantial adverse effects. This double-blind study, performed before the routine availability of highly active antiretroviral therapy, was designed to compare the efficacy and safety of liposomal amphotericin B to conventional amphotericin deoxycholate in patients with acquired immunodeficiency syndrome (AIDS) and acute cryptococcal meningitis. METHODS. Patients were randomized (ratio, 1:1:1) from multiple sites in the United States and Canada to receive either amphotericin B at 0.7 mg/kg/day (n = 87), liposomal amphotericin B at 3 mg/kg/day (n = 86), or liposomal amphotericin B at 6 mg/kg/day (n = 94). RESULTS. Efficacy was similar among all 3 treatment groups. The overall incidence of infusion-related reactions was significantly lower for both the 3 mg/kg/day and 6 mg/kg/day dosages of liposomal amphotericin B, compared with conventional amphotericin B (P < .001). Significantly fewer patients who received the 3 mg/kg/day dosage of liposomal amphotericin B developed nephrotoxicity, indicated by a doubling of the serum creatinine value, compared with recipients of conventional amphotericin B (P = .004). Overall mortality at 10 weeks was 11.6%, with no significant differences among the treatment groups. CONCLUSIONS. Liposomal amphotericin B provides an equally efficacious alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis. Liposomal amphotericin B at a dosage of 3 mg/kg/day is accompanied by significantly fewer adverse effects.

Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children

“…There continues to be considerable uncertainty regarding the lowest effective dose of LAmB that achieves adequate antifungal effect. As a result, doses of 1 to 15 mg kg Ϫ1 have been studied in a range of clinical settings, including empirical therapy, invasive aspergillosis, invasive candidiasis, and cryptococcal meningoencephalitis (11)(12)(13)(14).…”

Real-Time Treatment Guidelines: Considerations during the Exserohilum rostratum Outbreak in the United States

“…Even with these precautions, the nephrotoxicity of lipid-associated AmB often precludes prolonged administration, and therefore, transition to a less-toxic alternative is essential for patients who require longterm therapy. The expert advisory group supported the use of liposomal AmB specifically over other AmB formulations because of greater experience with this agent in human central nervous system infections (16,17).…”

British HIV Association opportunistic infection guidelines: in defence of amphotericin B deoxycholate

“…A subsequent larger RCT comparing AmBd at 0.7 mg/kg/day with AmBisome at 3 or 6 mg/kg/ day found no difference in efficacy, but reduced nephrotoxicity with AmBisome [5]. Neither trial included 5FC as a second drug.…”