WARNINGS
Anaphylaxis has been reported with amphotericin B deoxycholate and other amphotericin B-containing drugs, including Am B isome. If a severe anaphylactic reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusions of Am B isome.
PRECAUTIONS
GENERAL
As with any amphotericin B-containing product the drug should be administered by medically trained personnel. During the initial dosing period, patients should be under close clinical observation. Am B isome has been shown to be significantly less toxic than amphotericin B deoxycholate; however, adverse events may still occur.
LABORATORY TESTS
Patient management should include laboratory evaluation of renal, hepatic and hematopoietic function, and serum electrolytes (particularly magnesium and potassium).
DRUG INTERACTIONS
No formal clinical studies of drug interactions have been conducted with Am B isome. However, the following drugs are known to interact with amphotericin B and may interact with Am B isome. Antineoplastic agents: Concurrent use of antineoplastic agents may enhance the potential for renal toxicity, bronchospasm, and hypotension. Antineoplastic agents should be given concomitantly with caution. Corticosteroids and corticotropin (ACTH): Concurrent use of corticosteroids and ACTH may potentiate hypokalemia which could predispose the patient to cardiac dysfunction. If used concomitantly, serum electrolytes and cardiac function should be closely monitored. Digitalis glycosides: Concurrent use may induce hypokalemia and may potentiate digitalis toxicity. When administered concomitantly, serum potassium levels should be closely monitored. Flucytosine: Concurrent use of flucytosine may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion.
Azoles (e.g. ketoconazole, miconazole, clotrimazole, fluconazole, etc.): In vitro and in vivo animal studies of 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. Leukocyte transfusions: Acute pulmonary toxicity has been reported in patients simultaneously receiving intravenous amphotericin B and leukocyte transfusions. Other nephrotoxic medications: Concurrent use of amphotericin B and other nephrotoxic medications may enhance the potential for drug-induced renal toxicity. 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) due to hypokalemia. When administered concomitantly, serum potassium levels should be closely monitored.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
No long term studies in animals have been performed to evaluate carcinogenic potential of Am B isome. Am B isome has not been tested to determine its mutagenic potential. A Segment I Reproductive Study in rats found an abnormal estrous cycle (prolonged diestrus) and decreased number of corpora lutea in the high dose groups (10 and 15 mg/kg, doses equivalent to human doses of 1.6 and 2.4 mg/kg based on body surface area considerations). Am B isome did not affect fertility or days to copulation. There were no effects on male reproductive function.
PREGNANCY CATEGORY B
There have been no adequate and well-controlled studies of Am B isome in pregnant women. Systemic fungal infections have been successfully treated in pregnant women with amphotericin B deoxycholate, but the number of cases reported has been small.
Segment II studies in both rats and rabbits have concluded that Am B isome had no teratogenic potential in these species. In rats, the maternal non-toxic dose of Am B isome was estimated to be 5 mg/kg (equivalent to 0.16 to 0.8 times the recommended human clinical dose range of 1 to 5 mg/kg) and in rabbits, 3 mg/kg (equivalent to 0.2 to 1 times the recommended human clinical dose range), based on body surface area correction. Rabbits receiving the higher doses, (equivalent to 0.5 to 2 times the recommended human dose) of Am B isome experienced a higher rate of spontaneous abortions than did the control groups. Am B isome should only be used during pregnancy if the possible benefits to be derived outweigh the potential risks involved.
NURSING MOTHERS
Many drugs are excreted in human milk. However, it is not known whether Am B isome is excreted in human milk. Due to the potential for serious adverse reactions in breast-fed infants, a decision should be made whether to discontinue nursing or whether to discontinue the drug, taking into account the importance of the drug to the mother.
PEDIATRIC USE
Pediatric patients, age 1 month to 16 years, with presumed fungal infection (empirical therapy), confirmed systemic fungal infections or with visceral leishmaniasis have been successfully treated with Am B isome. In studies which included 302 pediatric patients administered Am B isome there was no evidence of any differences in efficacy or safety of Am B isome compared to adults. Since pediatric patients have received Am B isome at doses comparable to those used in adults on a per kilogram body weight basis, no dosage adjustment is required in this population. Safety and effectiveness in pediatric patients below the age of one month has not been established.
(See DESCRIPTION OF CLINICAL STUDIES -- Empirical Therapy in Febrile Neutropenic Patients and DOSAGE AND ADMINISTRATION.)
ELDERLY PATIENTS
Experience with Am B isome in the elderly (65 years or older) comprised 72 patients. It has not been necessary to alter the dose of Am B isome for this population. As with most other drugs, elderly patients receiving Am B isome should be carefully monitored.
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