No

Antifungal Agent, Parenteral

Treatment of aspergillosis or any type of progressive fungal infection in patients who are refractory to or intolerant of conventional amphotericin B therapy

B

Breast-feeding/lactation: Due to limited data, consider discontinuing nursing during therapy

Hypersensitivity to amphotericin or any component in the formulation

Anaphylaxis has been reported with other amphotericin B-containing drugs. Facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. If severe respiratory distress occurs, the infusion should be immediately discontinued. During the initial dosing, the drug should be administered under close clinical observation. Acute reactions (including fever and chills) may occur 1-2 hours after starting an intravenous infusion. These reactions are usually more common with the first few doses and generally diminish with subsequent doses. Pulmonary reactions may occur in neutropenic patients receiving leukocyte transfusions; separation of the infusions as much as possible is advised.

>10%:

Central nervous system: Chills, fever

Renal: Increased serum creatinine

1% to 10%:

Cardiovascular: Hypotension, cardiac arrest

Central nervous system: Headache, pain

Dermatologic: Rash

Endocrine & metabolic: Bilirubinemia, hypokalemia, acidosis

Gastrointestinal: Nausea, vomiting, diarrhea, gastrointestinal hemorrhage, abdominal pain

Renal: Renal failure

Respiratory: Respiratory failure, dyspnea, pneumonia

Increased nephrotoxicity: Aminoglycosides, cyclosporine, other nephrotoxic drugs

Potentiation of hypokalemia: Corticosteroids, corticotropin

Increased digitalis and neuromuscular-blocking agent toxicity due to hypokalemia

Decreased effect: Pharmacologic antagonism may occur with azole antifungal agents (eg, miconazole, ketoconazole)

Pulmonary toxicity has occurred with concomitant administration of amphotericin B and leukocyte transfusions

100 mg vials in 20 mL of suspension in single-use vials (no preservative is present). Intact vials should be stored at 2°C to 8°C (35°F to 46°F) and protected from exposure to light; do not freeze intact vials. Shake the vial gently until there is no evidence of any yellow sediment at the bottom. Withdraw the appropriate dose and filter the contents (5 micron filter) prior to dilution. Dilute into D₅W to a final concentration of 1 mg/mL. For pediatric patients and patients with cardiovascular disease, the drug may be diluted with D₅W to a final concentration of 2 mg/mL.

Do not use an in-line filter <5 microns

Diluted solution is stable for up to 15 hours at 2°C to 8°C (38°F to 46°F) and an additional 6 hours at room temperature

Binds to ergosterol altering cell membrane permeability in susceptible fungi and causing leakage of cell components with subsequent cell death

Distribution: V_d: Increases with increasing doses; reflects increased uptake by tissues (131 L/kg with 5 mg/kg/day)

Half-life: ~24 hours

Clearance: Increases with increasing doses [400 mL/hour/kg (with 5 mg/kg/day)]

Children and Adults: I.V.:

Range: 2.5-5 mg/kg/day as a single infusion

Dosing adjustment in renal impairment: None necessary; effects of renal impairment are not currently known

Hemodialysis: No supplemental dosage necessary

Peritoneal dialysis: No supplemental dosage necessary

Continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD): No supplemental dosage necessary

Renal function (monitor frequently during therapy), electrolytes (especially potassium and magnesium), liver function tests, temperature, PT/PTT, CBC; monitor input and output; monitor for signs of hypokalemia (muscle weakness, cramping, drowsiness, EKG changes, etc)

Sedation is common; may cause delirium

May cause bone marrow suppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Infusion therapy may take several months. Maintain good personal hygiene to reduce spread and recurrence of lesions. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience postural hypotension (use caution when changing from lying or sitting position to standing or when climbing stairs); nausea or vomiting (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report chest pain or palpitations, chills or fever, skin rash, muscle cramping or weakness, alteration in voiding patterns, CNS disturbances, pain at injection site, persistent GI disturbance, or other adverse reactions. Breast-feeding precautions: Do not breast-feed.

I.V. therapy may take several months; personal hygiene is very important to help reduce the spread and recurrence of lesions; most skin lesions require 1-3 weeks of therapy; report any hearing loss

Injection: 5 mg/mL (20 mL)

De Marie S, "Clinical Use of Liposomal and Lipid-Complexed Amphotericin B," J Antimicrob Chemother, 1994, 33(5):907-16.

Hiemenz JW and Walsh TJ, "Lipid Formulations of Amphotericin B: Recent Progress and Future Directions," Clin Infect Dis, 1996, 22 Suppl 2:S133-44.

Kline S, Larsen TA, Fieber L, et al, "Limited Toxicity of Prolonged Therapy With High Doses of Amphotericin B Lipid Complex," Clin Infect Dis, 1995, 21(5):1154-8.

Patel R, "Antifungal Agents. Part I. Amphotericin B Preparations and Flucytosine," Mayo Clin Proc, 1998, 73(12):1205-25.

Rapp RP, Gubbins PO, and Evans ME, "Amphotericin B Lipid Complex," Ann Pharmacother, 1997, 31(10):1174-86.

Slain D, "Lipid-Based Amphotericin B for the Treatment of Fungal Infections," Pharmacotherapy, 1999, 19(3):306-23.