INDICATIONS & USAGE Amphotericin B for Injection USP should be administered primarily to patients with progressive, potentially life-threatening fungal infections.

This potent drug should not be used to treat noninvasive fungal infections, such as oral thrush, vaginal candidiasis and esophageal candidiasis in patients with normal neutrophil counts.

Amphotericin B for Injection USP is specifically intended to treat potentially life-threatening fungal infections: aspergillosis, cryptococcosis (torulosis), North American blastomycosis, systemic candidiasis, coccidioido-mycosis, histoplasmosis, zygomycosis including mucormycosis due to susceptible species of the genera Absidia , Mucor and Rhizopus , and infections due to related susceptible species of Conidiobolus and Basidiobolus , and sporotrichosis.

Amphotericin B may be useful in the treatment of American mucocutaneous leishmaniasis, but it is not the drug of choice as primary therapy.

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 for Injection overdose, which can result in potentially fatal cardiac or cardiopulmonary arrest.

Verify the product name and dosage dosage pre-administration, especially if dose exceeds 1.5 mg/kg.

(see OVERDOSAGE and DOSAGE AND ADMINISTRATION )

ADVERSE REACTIONS 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 (see PRECAUTIONS: Drug Interactions ).

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: General (body as a whole): fever (sometimes accompanied by shaking chills usually occurring within 15 to 20 minutes after initiation of treatment); malaise; weight loss.

Cardiopulmonary: hypotension; tachypnea.

Gastrointestinal: anorexia; nausea; vomiting; diarrhea; dyspepsia; cramping epigastric pain.

Hematologic: normochromic, normocytic anemia.

Local: pain at the injection site with or without phlebitis or thrombophlebitis.

Musculoskeletal: generalized pain, including muscle and joint pains.

Neurologic: headache.

Renal: decreased renal function and renal function abnormalities including: azotemia, hypokalemia, hyposthenuria, renal tubular acidosis; and 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: General (body as a whole): flushing.

Allergic: anaphylactoid and other allergic reactions; bronchospasm; wheezing.

Cardiopulmonary: cardiac arrest; shock; cardiac failure; pulmonary edema; hypersensitivity pneumonitis; arrhythmias, including ventricular fibrillation; dyspnea; hypertension.

Dermatologic: rash, in particular maculopapular; pruritus.

Skin exfoliation, toxic epidermal necrolysis, and Stevens-Johnson syndrome have been reported during post-marketing surveillance.

Gastrointestinal: acute liver failure; hepatitis; jaundice; hemorrhagic gastroenteritis; melena.

Hematologic: agranulocytosis; coagulation defects; thrombocytopenia; leukopenia; eosinophilia; leukocytosis.

Neurologic: convulsions; hearing loss; tinnitus; transient vertigo; visual impairment; diplopia; peripheral neuropathy; encephalopathy (see PRECAUTIONS ); other neurologic symptoms.

Renal: acute renal failure; anuria; oliguria.

Nephrogenic diabetes insipidus has been reported during post-marketing surveillance.

Altered Laboratory Findings Serum Electrolytes: Hypomagnesemia; hypo- and hyperkalemia; hypocalcemia.

Liver Function Tests: Elevations of AST, ALT, GGT, bilirubin, and alkaline phosphatase.

Renal Function Tests: Elevations of BUN and serum creatinine.