University of Pennsylvania Medical Center Guidelines for Antibiotic Use

 

RECOMMENDATIONS FOR THE ADMINISTRATION AND DOSING OF

AMPHOTERICIN B

Immediate Adverse Effects and Premedication

Acute reactions to amphotericin B are seen within 90 minutes of the infusion and usually remit by 3-4 hours. Most common is fever with or without rigors; hypotension and anaphylaxis are rare. Up to 20% of patients will have minimal or no immediate infusion-related adverse reactions. Tolerance to the immediate reactions usually develops over time. Therefore, if premedications are used early in the treatment course, their need should be reevaluated weekly (consider withholding premedications after several days if the infusion related adverse effects have resolved).

SUGGESTED PREMEDICATIONS:

Acetaminophen 650-1000 mg po/pr 30 minutes prior to amphotericin B (other Non Steroidal Antiinflammatory Drugs (NSAIDS) may be used if not contraindicated).

Hydrocortisone: if patients experience severe rigors with previous infusion, start at 25 mg iv 30 minutes prior to amphotericin B (may increase to 50 mg). Reassess the need for hydrocortisone every 3 to 7 days.

NOTE: Hydrocortisone premedication should not be prescribed to patients already receiving corticosteroids. Please do not mix hydrocortisone with amphotericin B in the same bag.

SUGGESTED PRN ORDERS:

Meperidine: 25 mg iv every 15 minutes prn rigors, up to 100 mg over 1 hour. This should not be used as a premedication; only as a treatment for rigors (use with caution in patients with renal insufficiency).

Other Adverse Events

Nephrotoxicity

Renal insufficiency (with associated electrolyte disturbances) is frequent and often stabilizes at a creatinine of 2-3 mg/dl. It is usually reversible after cessation of the drug. Sodium loading may minimize azotemia therefore it is recommended to administer 500 ml of normal saline both before and after amphotericin B infusion. If patient is unable to tolerate a full fluid/sodium load, consider 250 ml before and after the infusion. Patients who can not tolerate a fluid/sodium load should not receive sodium loading. Other nephrotoxic drugs such as aminoglycosides, NSAIDS, furosemide, and cisplatin can add to the azotemia and should be avoided if possible. Doubling the dosage of amphotericin B and administering it every other day will help diminish nausea and anorexia, but will not impact on azotemia. If azotemia occurs with a serum creatinine 3 mg/dl, the dose of amphotericin B may be reduced or held after a careful assessment of the risks versus benefits to the patient (discuss with Infectious Disease consultant).

Phlebitis

Phlebitis can occur with infusion via peripheral veins. If peripherally administered, concentration should not exceed 0.1 mg/ml D5W. Although no controlled data support its use, the manufacturer recommends that heparin 1000 units/L be added to the solution. If phlebitis develops, decreasing the rate of infusion or further dilution may help.

Other less common adverse effects

Anemia

Distal renal tubular acidosis

Pulmonary infiltrates in patients receiving concomitant WBC transfusion

Recommended Dosing

Optimal dosing of amphotericin B for most fungal infections is not known. The following are suggested guidelines:

Oral/esophageal candidiasis = 0.1-0.3 mg/kg/d

Empiric therapy in febrile neutropenic patient = 0.5 to 0.7 mg/kg/d

Documented systemic candidiasis = 0.5-1 mg/kg/d

Presumptive or documented aspergillosis = 1-1.5 mg/kg/d

Alternate day therapy = double the daily dose to a maximum of 1.5 mg/kg/d

**maximum daily dose should not exceed 1.5 mg/kg/d

**dosage adjustment is not necessary for renal insufficiency, hemodialysis or liver failure

Administration

Prior to starting treatment, a test dose of 1 mg of amphotericin B is usually infused over 1 hour in order to assess the patient for immediate adverse events. The patient's vital signs are monitored every 15 minutes for an hour. If no serious adverse reactions occur, the remainder of the desired daily dose is administered over 2-6 hours as follows:

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