IAB
IAB - General Information
IAB 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.
Pharmacology of IAB
IAB 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.
IAB for patients
WARNINGS
Amphotericin B is frequently the only effective treatment available for potentially life-threatening fungal disease. In each case, its possible life-saving benefit must be balanced against its untoward and dangerous side effects.
PRECAUTIONS
General
Amphotericin B should be administered intravenously under close clinical observation by medically trained personnel. It should be reserved for treatment of patients with progressive, potentially life-threatening fungal infections due to susceptible organisms.
Acute reactions including fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, and tachypnea are common 1 to 3 hours after starting an intravenous infusion. These reactions are usually more severe with the first few doses of amphotericin B and usually diminish with subsequent doses.
Rapid intravenous infusion has been associated with hypotension, hypokalemia, arrhythmias, and shock and should, therefore, be avoided.
Amphotericin B should be used with care in patients with reduced renal function; frequent monitoring of renal function is recommended (see Laboratory Tests below and ADVERSE REACTIONS). In some patients hydration and sodium repletion prior to amphotericin B administration may reduce the risk of developing nephrotoxicity. Supplemental alkali medication may decrease renal tubular acidosis complications.
Since acute pulmonary reactions have been reported in patients given amphotericin B during or shortly after leukocyte transfusions, it is advisable to temporarily separate these infusions as far as possible and to monitor pulmonary function.
Leukoencephalopathy has been reported following use of amphotericin B. Literature reports have suggested that total body irradiation may be a predisposition.
Whenever medication is interrupted for a period longer than seven days, therapy should be resumed by starting with the lowest dosage level, e. g., 0.25 mg/kg of body weight, and increased gradually as outlined under DOSAGE AND ADMINISTRATION.
Laboratory Tests
Renal function should be monitored frequently during amphotericin B therapy. It is also advisable to monitor on a regular basis liver function, serum electrolytes (particularly magnesium and potassium), blood counts, and hemoglobin concentrations. Laboratory test results should be used as a guide to subsequent dosage adjustments.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term studies in animals have been performed to evaluate carcinogenic potential. There also have been no studies to determine mutagenicity or whether this medication affects fertility in males or females.
Pregnancy: Teratogenic Effects, Pregnancy Category B
Reproduction studies in animals have revealed no evidence of harm to the fetus due to amphotericin B for injection. Systemic fungal infections have been successfully treated in pregnant women with amphotericin B for injection without obvious effects to the fetus, but the number of cases reported has been small. Because animal reproduction studies are not always predictive of human response, and adequate and well-controlled studies have not been conducted in pregnant women, this drug should be used during pregnancy only if clearly indicated.
Nursing Mothers
It is not know whether amphotericin B is excreted in human milk. Because many drugs are excreted in human milk and considering the potential toxicity of amphotericin B, it is prudent to advise a nursing mother to discontinue nursing.
IAB 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.
IAB 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.
Additional information about IAB
IAB Indication: Used to treat potentially life threatening fungal infections.
Mechanism Of Action: IAB 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. IAB, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.
Drug Interactions: Cyclosporine Monitor for nephrotoxicity
Food Interactions: Not Available
Generic Name: Amphotericin B
Synonyms: AMPH-B; Amphortericin B; Amphotericine B; Liposomal Amphotericin B
Drug Category: Amebicides; Anti-Bacterial Agents; Antifungal Agents; Antiprotozoal Agents
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Amphotericin B: ABLC; Abelcet; AmB; AmBisome; Ampho-Moronal; Amphocin; Amphotec; Amphotericin; Amphozone; Fungilin; Fungisone; Fungizone; Fungizone Intravenous; HSDB 3008 IAB; Halizon; IAB; LNS-AmB; Mysteclin-F; Tegopen;
Absorption: Bioavailability is 100% for intravenous infusion.
Toxicity (Overdose): Oral, rat: LD50 = >5 gm/kg. Amphotericin B overdoses can result in cardio-respiratory arrest.
Protein Binding: Highly bound (>90%) to plasma proteins.
Biotransformation: Exclusively renal
Half Life: An elimination half-life of approximately 15 days follows an initial plasma half-life of about 24 hours.
Dosage Forms of IAB: Powder, for solution Intravenous
Powder, for suspension Intravenous
Suspension Intravenous
Chemical IUPAC Name: (1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
Chemical Formula: C47H73NO17
Amphotericin B on Wikipedia: https://en.wikipedia.org/wiki/Amphotericin_B
Organisms Affected: Various Fungus Species
