No

Antifungal Agent, Parenteral

Empirical therapy for presumed fungal infection in febrile, neutropenic patients. Treatment of patients with Aspergillus species, Candida species and/or Cryptococcus species infections refractory to amphotericin B desoxycholate, or in patients where renal impairment or unacceptable toxicity precludes the use of amphotericin B desoxycholate. Treatment of visceral leishmaniasis. In immunocompromised patients with visceral leishmaniasis treated with amphotericin B, liposomal, relapse rates were high following initial clearance of parasites.

B

In those patients who have demonstrated or have known hypersensitivity to amphotericin B or any other constituents of the product unless, in the opinion of the treating physician, the benefit of therapy outweighs the risk

Anaphylaxis has been reported with amphotericin B desoxycholate and other amphotericin B-containing drugs. Facilities for cardiopulmonary resuscitation should be available during administration due to the possibility of anaphylactic reaction. As with any amphotericin B-containing product the drug should be administered by medically trained personnel. During the initial dosing period, patients should be under close clinical observation. Amphotericin B, liposomal has been shown to be significantly less toxic than amphotericin B desoxycholate; however, adverse events may still occur. If severe respiratory distress occurs, the infusion should be immediately discontinued and the patient should not receive further infusions. 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.

>10%:

Central nervous system: Chills, fever

Renal: Increased serum creatinine

Miscellaneous: Multiple organ failure

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

The toxicity due to overdose has not been defined. Repeated daily doses up to 7.5 mg/kg have been administered in clinical trials with no reported dose-related toxicity.

If overdosage should occur, cease administration immediately. Symptomatic supportive measures should be instituted. Particular attention should be given to monitoring renal function.

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

Must be reconstituted using sterile water for injection, USP (without a bacteriostatic agent). Follow package insert instructions carefully for preparation. Do not reconstitute with saline or add saline to the reconstituted concentration, or mix with other drugs. The use of any solution other than those recommended, or the presence of a bacteriostatic agent in the solution, may cause precipitation.

Injection should commence within 6 hours of dilution with 5% dextrose injection.

An in-line membrane filter may be used for the intravenous infusion; provided, THE MEAN PORE DIAMETER OF THE FILTER SHOULD NOT BE LESS THAN 1 (one) MICRON.

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

Distribution: V_d: 131 L/kg

Half-life, terminal elimination: 174 hours

Poorly dialyzed

Children and Adults: I.V.:

Empiric therapy: Recommended initial dose: 3 mg/kg/day

Systemic fungal infections ( Aspergillus, Candida, Cryptococcus): Recommended initial dose of 3-5 mg/kg/day

Treatment of visceral leishmaniasis: Amphotericin B liposomal achieved high rates of acute parasite clearance in immunocompetent patients when total doses of 12-30 mg/kg were administered. Most of these immunocompetent patients remained relapse-free during follow-up periods of 6 months or longer. While acute parasite clearance was achieved in most of the immunocompromised patients who received total doses of 30-40 mg/kg, the majority of these patients were observed to relapse in the 6 months following the completion of therapy.

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

Hemodialysis: No supplemental dosage necessary

Peritoneal dialysis effects: 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

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: 50 mg

Emminger W, Graninger W, Emminger-Schmidmeir W, et al, "Tolerance of High Doses of Amphotericin B by Infusion of a Liposomal Formulation in Children With Cancer," Ann Hematol, 1994, 68:27-31.

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

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

Ringden O, Andstrom E, Remberger M, et al, "Safety of Liposomal Amphotericin B (AmBisome®) In 187 Transplant Recipients Treated With Cyclosporin," Bone Marrow Transplant, 1994, 14 Suppl 5:S10-4.

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

Walsh TJ, Finberg RW, Arndt C, et al, "Liposomal Amphotericin B for Empirical Therapy in Patients With Persistent Fever and Neutropenia," N Engl J Med, 1999, 340:764-71.