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.
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.
Gastrointestinal: acute liver failure; hepatitis; jaundice; hemorrghagic 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.
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.