Amphotericin B liposome

Intravenous infusion should be given over a period of approximately 2 to 6 hours (depending on the dose) observing the usual precautions for intravenous therapy (see PRECAUTIONS: General ). The recommended concentration for intravenous infusion is 0.1 mg/mL (1mg/10mL). Since patient tolerance varies greatly, the dosage of amphotericin B must be individualized and adjusted according to the patient's clinical status (e.g., site and severity of infection, etiologic agent, cardio-renal function, etc.).

A single intravenous test dose (1 mg in 20 mL of 5% dextrose solution) administered over 20 to 30 minutes may be preferred. The patient's temperature, pulse, respiration, and blood pressure should be recorded every 30 minutes for 2 to 4 hours. In patients with good cardio-renal function and a well tolerated test dose , therapy is usually initiated with a daily dose of 0.25 mg/kg of body weight.

However, in those patients having severe and rapidly progressive fungal infection , therapy may be initiated with a daily dose of 0.3 mg/kg of body weight. In patients with impaired cardio-renal function or a severe reaction to the test dose , therapy should be initiated with smaller daily doses (i.e., 5 to 10 mg). Depending on the patient's cardio-renal status (see PRECAUTIONS: Laboratory Tests ), doses may gradually be increased by 5 to 10 mg per day to final daily dosage of 0.5 to 0.7 mg/kg.

In contradistinction, pulmonary phycomycosis, which is more common in association with hematologic malignancies, is often an incidental finding at autopsy. A cumulative dose of at least 3 g of amphotericin B is recommended to treat rhinocerebral phycomycosis. Although a total dose of 3 to 4 g will infrequently cause lasting renal impairment, this would seem a reasonable minimum where there is clinical evidence of invasion of deep tissue.

DOSAGE & ADMINISTRATION ** VERIFY PRODUCT NAME AND DOSAGE. ** CAUTION: Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded. Amphotericin B overdoses can result in potentially fatal cardiac or cardiopulmonary arrest (see WARNINGS and OVERDOSAGE ). Amphotericin B for Injection should be administered by slow intravenous infusion.

Since rhinocerebral phycomycosis usually follows a rapidly fatal course, the therapeutic approach must necessarily be more aggressive than that used in more indolent mycoses. Preparation of Solutions Reconstitute as follows: An initial concentrate of 5 mg amphotericin B per mL is first prepared by rapidly expressing 10 mL Sterile Water for Injection USP without a bacteriostatic agent directly into the lyophilized cake, using a sterile needle (minimum diameter: 20 gauge) and syringe.

Shake the vial immediately until the colloidal solution is clear. The infusion solution, providing 0.1 mg amphotericin B per mL, is then obtained by further dilution (1:50) with 5% Dextrose Injection USP of pH above 4.2. The pH of each container of Dextrose Injection should be ascertained before use. Commercial Dextrose Injection usually has a pH above 4.2; however, if it is below 4.2, then 1 or 2 mL of buffer should be added to the Dextrose Injection before it is used to dilute the concentrated solution of amphotericin B.

All entries into the vial or into the diluents must be made with a sterile needle. Do not reconstitute with saline solutions. The use of any diluent other than the ones recommended or the presence of a bacteriostatic agent (e.g., benzyl alcohol) in the diluent may cause precipitation of the antibiotic. Do not use the initial concentrate or the infusion solution if there is any evidence of precipitation or foreign matter in either one.

An in-line membrane filter may be used for intravenous infusion of amphotericin B; however, the mean pore diameter of the filter should not be less than 1.0 micron in order to assure passage of the antibiotic dispersion.