DOSAGE AND ADMINISTRATION
**VERIFY PRODUCT NAME AND
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
cardiorespiratory arrest (see WARNINGS and OVERDOSAGE).
FUNGIZONE Intravenous (Amphotericin B for Injection) should be administered
by slow intravenous infusion. 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 (1 mg/10 mL). 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,
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.
There are insufficient data
presently available to define total dosage requirements and duration of
treatment necessary for eradication of specific mycoses. The optimal dose is
unknown. Total daily dosage may range up to 1.0 mg/kg per day or up to 1.5
mg/kg when given on alternate days.
Therapy with intravenous
amphotericin B for sporotrichosis has ranged up to 9 months with a total dose
up to 2.5 g.
Aspergillosis has been treated
with amphotericin B intravenously for a period up to 11 months with a total
dose up to 3.6 g.
This fulminating disease
generally occurs in association with diabetic ketoacidosis. It is, therefore,
imperative that diabetic control be restored in order for treatment with
FUNGIZONE (amphotericin b) Intravenous to be successful. 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. 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. The recommended buffer has the following composition:
Dibasic sodium phosphate
(anhydrous) 1.59 g
Monobasic sodium phosphate
(anhydrous) 0.96 g
Water for Injection, USP qs
The buffer should be sterilized
before it is added to the Dextrose Injection, either by filtration through a
bacterial retentive stone, mat, or membrane, or by autoclaving for 30 minutes
at 15 lb pressure (121° C).
CAUTION: Aseptic technique
must be strictly observed in all handling, since no preservative or
bacteriostatic agent is present in the antibiotic or in the materials used to
prepare it for administration. 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
(Amphotericin B for Injection, USP)
Available as single vials providing 50 mg amphotericin B as
a yellow to orange lyophilized cake (which may partially reduce to powder following
manufacture). NDC 0003-0437-30.
Prior to reconstitution
FUNGIZONE (amphotericin b) Intravenous should be stored in the refrigerator, protected against
exposure to light. The concentrate (5 mg amphotericin B per mL after
reconstitution with 10 mL Sterile Water for Injection, USP) may be stored in
the dark, at room temperature for 24 hours, or at refrigerator temperatures for
1 week with minimal loss of potency and clarity. Any unused material should
then be discarded. Solutions prepared for intravenous infusion (0.1 mg or less
amphotericin B per mL) should be used promptly after preparation and should be
protected from light during administration.
Manufactured by: Ben Venue Laboratories, Inc., Bedford, OH 44146
USA. Manufactured for: Bristol-Myers Squibb Company, Princeton, NJ 08543 USA.
Distributed by: Geneva Pharmaceuticals, Inc., Dayton, NJ 08810 USA. Rev September