Amphotericin B Injection  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. 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 7 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. 

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. 

onitoring of renal function is recommended in patients requiring any combination of nephrotoxic medications (see 
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. 

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 known 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. 

Pediatric Use 

Safety  and effectiveness in pediatric patients have  not been established through adequate and well-controlled studies. Systemic fungal infections have been successfully treated in pediatric patients  without reports of unusual side effects. Amphotericin B  for Injection when administered to pediatric patients should  be limited  to the smallest dose compatible with  an effective therapeutic regimen.