- Amphotericin B, a polyene antifungal agent, has long been considered the gold standard for treating serious systemic fungal infections. Despite its broad-spectrum efficacy, its clinical utility is significantly limited by its potential for severe toxicity. The toxicity profile of Amphotericin B encompasses a wide range of adverse effects, the most prominent being nephrotoxicity, infusion-related reactions, electrolyte imbalances, and, less commonly, hematologic and hepatic toxicities.
- Nephrotoxicity is the most significant and dose-limiting adverse effect of Amphotericin B. It occurs in a majority of patients receiving the conventional deoxycholate formulation. The drug induces renal vasoconstriction, reducing glomerular filtration rate and causing direct tubular epithelial cell damage. This can lead to acute kidney injury, with manifestations such as elevated serum creatinine, decreased urine output, and renal tubular acidosis. Chronic use may result in irreversible kidney damage. Concomitant use of other nephrotoxic drugs (e.g., aminoglycosides, cyclosporine) exacerbates this risk. Lipid-based formulations of Amphotericin B (such as liposomal Amphotericin B and Amphotericin B lipid complex) have been developed to reduce nephrotoxicity by altering the drug’s tissue distribution, although they may still cause some degree of renal impairment.
- Infusion-related reactions are another common adverse effect, typically occurring within the first few hours of administration. These include fever, chills, rigors, hypotension, tachypnea, nausea, and vomiting. These reactions are thought to be due to pro-inflammatory cytokine release, particularly tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1). Premedication with antipyretics, antihistamines, corticosteroids, or meperidine can help mitigate these symptoms. Slowing the infusion rate may also alleviate the severity of reactions.
- Electrolyte disturbances, particularly hypokalemia and hypomagnesemia, are frequently observed with Amphotericin B use. These abnormalities result from renal tubular damage and increased urinary losses of potassium and magnesium. These disturbances can predispose patients to cardiac arrhythmias and neuromuscular symptoms, necessitating regular monitoring and supplementation as needed.
- Other notable but less common toxicities include hematologic effects such as anemia, which occurs due to decreased erythropoietin production secondary to renal toxicity. Hepatotoxicity is rare but can present with elevated liver enzymes. In rare instances, Amphotericin B can also cause thrombophlebitis at the site of infusion and anaphylactic reactions.
- Given its toxicity profile, close monitoring of renal function, electrolytes, and complete blood counts is essential during Amphotericin B therapy. Dose adjustment, hydration, and the use of lipid-based formulations can help manage and reduce the risk of adverse effects. Despite its drawbacks, Amphotericin B remains a vital agent in the management of life-threatening fungal infections, particularly in immunocompromised patients, where its benefits often outweigh its risks.
