Active ingredient: Amphotericin B - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Amebicides
• Anti-Bacterial Agents
• Antifungal Agents
• Antiprotozoal Agents

Dosage Forms

• Slow intravenous-infusion

Brands / Synonyms

Abelcet; ABLC; AM B Isome; AmB; AmBisome; AMPH-B; Ampho-Moronal; Amphocin; Amphortericin B; Amphotec; Amphotericin; Amphotericin B; Amphotericine B; Amphozone; Fungilin; Fungisone; Fungizone; Fungizone Intravenous; Halizon; HSDB 3008 IAB; IAB; Liposomal Amphotericin B; LNS-AmB; Mysteclin-F; Tegopen

Indications

Used to treat potentially life threatening fungal infections.

Pharmacology

Amphotericin B shows a high order of in vitro activity against many species of fungi. Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus are all inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible. Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses.

Mechanism of Action

Amphotericin B is fungistatic or fungicidal depending on the concentration obtained in body fluids and the susceptibility of the fungus. The drug acts by binding to sterols in the cell membrane of susceptible fungi with a resultant change in membrane permeability allowing leakage of intracellular components. Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of amphotericin B and the azoles. Amphotericin B, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.

Absorption

Bioavailability is 100% for intravenous infusion.

Toxicity

Oral, rat: LD₅₀ = >5 gm/kg. Amphotericin B overdoses can result in cardio-respiratory arrest.

Biotrnasformation / Drug Metabolism

Exclusively renal

Contraindications

This product is contraindicated in those patients who have shown hypersensitivity to amphotericin B or any other component in the formulation unless, in the opinion of the physician, the condition requiring treatment is life-threatening and amenable only to amphotericin B therapy.

Drug Interactions

When administered concurrently, the following drugs may interact with amphotericin B:

Antineoplastic agents: may enhance the potential for renal toxicity, bronchospasm and hypotension. Antineoplastic agents (e. g., nitrogen mustard, etc.) should be given concomitantly only with great caution.

Corticosteroids and Corticotropin (ACTH): may potentiate amphotericin B- induced hypokalemia which may predispose the patient to cardiac dysfunction. Avoid concomitant use unless necessary to control side effects of amphotericin B. If used concomitantly, closely monitor serum electrolytes and cardiac function.

Digitalis glycosides: amphotericin B-induced hypokalemia may potentiate digitalis toxicity. Serum potassium levels and cardiac function should be closely monitored and any deficit promptly corrected.

Flucytosine: while a synergistic relationship with amphotericin B has been reported, concomitant use may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion.

Imidazoles (e. g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.): in vitro and animal studies with the combination of amphotericin B and imidazoles suggest that imidazoles may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients.

Other nephrotoxic medications: agents such as aminoglycosides, cyclosporine, and pentamidine may enhance the potential for drug-induced renal toxicity, and should be used concomitantly only with great caution. Intensive monitoring of renal function is recommended in patients requiring any combination of nephrotoxic medications .

Skeletal muscle relaxants: amphotericin B-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g., tubocurarine). Serum potassium levels should be monitored and deficiencies corrected.

Leukocyte transfusions: acute pulmonary toxicity has been reported in patients receiving intravenous amphotericin B and leukocyte transfusions.