Amphotericin B and its Formulations

Amphotericin B and its Formulations

1. Introduction & historical context

• Amphotericin B is the prototype polyene macrolide antifungal and remains the gold standard of systemic antifungal pharmacotherapy for a wide range of deeply invasive mycoses, despite its considerable toxicity (G&G 14e Ch.61, pp.1193–4).
• Introduced as amphotericin B-deoxycholate in the late 1950s (conventional AmB), it was for many years the only efficacious antifungal drug available for systemic use (Katzung 16e Ch.48, pp.898; G&G 14e Ch.61, p.1193).
  • Around 1960, two key antifungal antibiotics entered Indian practice: amphotericin B for systemic mycosis and griseofulvin for dermatophytes (KDT 8e Ch.58, p.838).
• The rising incidence of life-threatening fungal infections (driven by immunocompromised populations — haematologic/solid-organ transplant, cancer chemotherapy, immunosuppressives, HIV-AIDS) has made AmB increasingly important in modern medicine; mortality of invasive fungal disease remains unacceptably high (G&G 14e Ch.61, p.1193).
• Despite the introduction of relatively non-toxic azoles and echinocandins that have displaced it for many indications, AmB's broad spectrum and fungicidal action keep it a useful agent for nearly all life-threatening mycoses (Katzung 16e Ch.48, pp.898–9, p.900).
• Source: obtained from the actinomycete Streptomyces nodosus (KDT 8e Ch.58, p.839; Padmaja 7e Ch.51, p.605; Katzung 16e Ch.48, p.898). Amphotericin A is also produced by S. nodosus but is not in clinical use; only amphotericin B is therapeutic (Katzung 16e Ch.48, p.898).