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Black Box Warning
WARNING
See full prescribing information for complete 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. Verify the product name and dosage pre-administration, especially if dose exceeds 1.5 mg/kg.
Amphotericin B for Injection should be administered by slow intravenous infusion. Intravenous infusion should be given over a period of approximately 2 to 6 hours (depending on the dose) observing the usual precautions for intravenous therapy. The recommended concentration for intravenous infusion is 0.1 mg/mL (1mg/10mL). Since patient tolerance varies greatly, the dosage of amphotericin B must be individualized and adjusted according to the patient's clinical status (e.g., site and severity of infection, etiologic agent, cardio-renal function, etc.). A single intravenous test dose (1 mg in 20 mL of 5% dextrose solution) administered over 20 to 30 minutes may be preferred. The patient's temperature, pulse, respiration, and blood pressure should be recorded every 30 minutes for 2 to 4 hours.
In patients with good cardio-renal function and a well tolerated test dose, therapy is usually initiated with a daily dose of 0.25 mg/kg of body weight. However, in those patients having severe and rapidly progressive fungal infection, therapy may be initiated with a daily dose of 0.3 mg/kg of body weight. In patients with impaired cardio-renal function or a severe reaction to the test dose, therapy should be initiated with smaller daily doses (i.e., 5 to 10 mg). Depending on the patient's cardio-renal status, doses may gradually be increased by 5 to 10 mg per day to final daily dosage of 0.5 to 0.7 mg/kg.
There are insufficient data presently available to define total dosage requirements and duration of treatment necessary for eradication of specific mycoses. The optimal dose is unknown. Total daily dosage may range up to 1.0 mg/kg per day or up to 1.5 mg/kg when given on alternate days.
Sporotrichosis: Therapy with intravenous amphotericin B for sporotrichosis has ranged up to nine months with a total dose up to 2.5 g.
Aspergillosis: Aspergillosis has been treated with amphotericin B intravenously for a period up to 11 months with a total dose up to 3.6 g.
Rhinocerebral phycomycosis: This fulminating disease generally occurs in association with diabetic ketoacidosis. It is, therefore, imperative that diabetic control be restored in order for treatment with Amphotericin B for Injection to be successful. In contradistinction, pulmonary phycomycosis, which is more common in association with hematologic malignancies, is often an incidental finding at autopsy. A cumulative dose of at least 3 g of amphotericin B is recommended to treat rhinocerebral phycomycosis. Although a total dose of 3 to 4 g will infrequently cause lasting renal impairment, this would seem a reasonable minimum where there is clinical evidence of invasion of deep tissue. Since rhinocerebral phycomycosis usually follows a rapidly fatal course, the therapeutic approach must necessarily be more aggressive than that used in more indolent mycoses.
Amphotericin B deoxycholate: 0.5–1.0 mg/kg daily IV
Amphotericin B Lipid Formulation: 3–5 mg/kg daily IV
Non–Guideline-Supported Use
Neonatal Candidiasis
Dosage: 3–5 mg/kg daily IV if no urinary tract involvement[12]
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.
Warnings
WARNING
See full prescribing information for complete 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. Verify the product name and dosage pre-administration, especially if dose exceeds 1.5 mg/kg.
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. Verify the product name and dosage especially if dose exceeds 1.5 mg/kg.
Adverse Reactions
Clinical Trials Experience
Although some patients may tolerate full intravenous doses of amphotericin B without difficulty, most will exhibit some intolerance, often at less than the full therapeutic dose. Tolerance may be improved by treatment with aspirin, antipyretics (e.g., acetaminophen), antihistamines, or antiemetics. Meperidine (25 to 50 mg IV) has been shown in some patients to decrease the duration of shaking chills and fever that may accompany the infusion of amphotericin B. Administration of amphotericin B on alternate days may decrease anorexia and phlebitis.
Intravenous administration of small doses of adrenal corticosteroids just prior to or during the Amphotericin B infusion may help decrease febrile reactions. Dosage and duration of such corticosteroid therapy should be kept to a minimum.
Addition of heparin (1000 units per infusion), and the use of a pediatric scalp-vein needle may lessen the incidence of thrombophlebitis. Extravasation may cause chemical irritation.
The adverse reactions most commonly observed are:
Body as a Whole
Fever (sometimes accompanied by shaking chills usually occurring within 15 to 20 minutes after initiation of treatment)
Nephrocalcinosis. These usually improve with interruption of therapy. However, some permanent impairment often occurs, especially in those patients receiving large amounts (over 5 g) of amphotericin B or receiving other nephrotoxic agents.
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.
The following adverse reactions have also been reported:
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.
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.
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.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): 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.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Amphotericin B in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Amphotericin B during labor and delivery.
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.
Geriatic Use
There is no FDA guidance on the use of Amphotericin B with respect to geriatric patients.
Gender
There is no FDA guidance on the use of Amphotericin B with respect to specific gender populations.
Race
There is no FDA guidance on the use of Amphotericin B with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Amphotericin B in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Amphotericin B in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Amphotericin B in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Amphotericin B in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral
Intravenous
Monitoring
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.
IV Compatibility
There is limited information regarding IV Compatibility of Amphotericin B in the drug label.
Overdosage
Amphotericin B overdoses can result in potentially fatal cardiac or cardiopulmonary arrest. If an overdose is suspected, discontinue therapy and monitor the patient's clinical status (e.g., cardiorespiratory, renal, and liver function, hematologic status, serum electrolytes) and administer supportive therapy, as required. Amphotericin B is not hemodialyzable. Prior to reinstituting therapy, the patient's condition should be stabilized (including correction of electrolyte deficiencies, etc.).
Pharmacology
There is limited information regarding Amphotericin B Pharmacology in the drug label.
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