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Amphotericin B (Amphotericin B) - Warnings and Precautions

 
 



BOXED WARNING

This drug should be used primarily for treatment of patients with progressive and potentially life-threatening fungal infections; it should not be used to treat noninvasive forms of fungal disease such as oral thrush, vaginal candidiasis and esophageal candidiasis in patients with normal neutrophil counts.

Amphotericin B for Injection should no be given in doses greater than 1.5 mg/kg.

EXERCISE CAUTION to prevent inadvertent overdosage, which may result in potentially fatal cardiac or cardiopulmonary arrest (see WARNINGS, OVERDOSAGE and DOSAGE AND ADMINISTRATION). Verify the product name and dosage pre-administration, especially if dose exceeds 1.5 mg/kg.

 

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.

EXERCISE CAUTION to prevent inadvertent Amphotericin B overdose, which may result in potentially fatal cardiac or cardiopulmonary arrest (see OVERDOSAGE and DOSAGE AND ADMINISTRATION). Verify the product name and dosage especially if dose exceeds 1.5 mg/kg.

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 (see INDICATIONS AND USAGE).

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 (see DOSAGE AND ADMINISTRATION).

Amphotericin B should be used with care in patients with reduced renal function; frequent monitoring of renal function is recommended (see PRECAUTIONS: Laboratory Tests 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 (see PRECAUTIONS: Drug Interactions).

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 (see ADVERSE REACTIONS).

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 (see ADVERSE REACTIONS).

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 immnocompromised 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 (see PRECAUTIONS: Laboratory Tests).

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 (see PRECAUTIONS: General).

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.

Page last updated: 2011-11-22

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