No

Antifungal Agent, Parenteral

Treatment of invasive aspergillosis in patients who have failed amphotericin B deoxycholate treatment, or who have renal impairment or experience unacceptable toxicity which precludes treatment with amphotericin B deoxycholate in effective doses.

B

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

Hypersensitivity to amphotericin B or its components

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. Infusion reactions, sometimes, severe, usually subside with continued therapy - manage with decreased rate of infusion and pretreatment with antihistamines/corticosteroids; 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

1% to 10%:

Cardiovascular: Hypotension, tachycardia

Central nervous system: Headache

Dermatologic: Rash

Endocrine & metabolic: Hypokalemia, hypomagnesemia

Gastrointestinal: Nausea, diarrhea, abdominal pain

Hematologic: Thrombocytopenia

Hepatic: LFT change

Neuromuscular & skeletal: Rigors

Renal: Elevated creatinine

Respiratory: Dyspnea

Symptoms of overdose include renal dysfunction, anemia, thrombocytopenia, granulocytopenia, fever, nausea, vomiting

Treatment is supportive

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

Store intact vials under refrigeration.

Reconstitute 50 mg and 100 mg vials with 10 mL and 20 mL of SWI, respectively. The reconstituted vials contain 5 mg/mL of amphotericin B. Shake the vial gently by hand until all solid particles have dissolved. After reconstitution, the solution should be refrigerated at 2°C to 8°C/36°F to 46°F and used within 24 hours.

Further dilute amphotericin B colloidal dispersion with dextrose 5% in water. Concentrations of 0.1-2 mg/mL in dextrose 5% in water are stable for 14 days at 4°C and 23°C if protected from light, however, due to the occasional formation of subvisual particles, solutions should be used within 48 hours.

Incompatible with sodium chloride solutions

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

Distribution: V_d: Total amphotericin B volume of distribution increases with increasing doses, reflects increasing uptake by tissues (with 4 mg/kg/day = 4 L/kg); predominantly distributed in the liver; concentrations in kidneys and other tissues are lower than observed with conventional amphotericin B

Half-life: 28-29 hours (increases with increasing doses)

Plasma concentration: Trough amphotericin B levels remain between 1-3 mcg/mL; little accumulation in plasma

Children and Adults: I.V.:

Range: 3-4 mg/kg/day (infusion of 1 mg/kg/hour); maximum: 7.5 mg/kg/day

Liver function tests, electrolytes, BUN, Cr, temperature, CBC, I/O, signs of hypokalemia (muscle weakness, cramping, drowsiness, EKG changes)

No information available to require special precautions

No effects or complications reported

This medication can only be administered by infusion and therapy may last several weeks. Maintain good 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; skin rash; chills or fever; persistent nausea, vomiting, or abdominal pain; sore throat; excessive fatigue; swelling of extremities or unusual weight gain; difficulty breathing; pain at infusion site; muscle cramping or weakness; or other adverse reactions. Breast-feeding precautions: Do not breast-feed.

May premedicate with acetaminophen and diphenhydramine 30 minutes prior to infusion; meperidine may help reduce rigors; avoid injection faster than 1 mg/kg/hour

Suspension for injection: 50 mg (20 mL); 100 mg (50 mL)

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

Lister J, "Amphotericin B Lipid Complex (Abelcet™) in the Treatment of Invasive Mycoses: The North American Experience," Eur J Haematol Suppl, 1996, 57:18-23.

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

Prentice HG, Hann IM, Herbrecht R, et al, "A Randomized Comparison of Liposomal Versus Conventional Amphotericin B for the Treatment of Pyrexia of Unknown Origin in Neurtopenic Patients," Br J Haematol, 1997, 98(3):711-8.

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