PRESENTATION: Sterile, powder for dispersion for infusion. Each vial
contains 50mg of amphotericin B (50,000 units), encapsulated in
liposomes.
INDICATIONS (adults and children aged 1 month to 18 years: 1)
Severe systemic and/or deep mycoses 2) Visceral leishmaniasis in
immunocompetent patients 3) Empirical treatment of presumed fungal
infections in febrile neutropenic patients, where the fever has failed to
respond to broad-spectrum antibiotics and appropriate investigations
have failed to define a bacterial or viral cause. Infections successfully
treated with AmBisome include: disseminated candidiasis,
aspergillosis, mucormycosis, chronic mycetoma, cryptococcal
meningitis and visceral leishmaniasis. AmBisome should not be used
to treat the common clinically inapparent forms of fungal disease which
show only positive skin or serologic tests.
DOSAGE/ADMINISTRATION: Preparation: Follow reconstitution
instructions exactly as per SmPC. Administration: intravenous infusion
over a 30 – 60 min period, or over a 2 hour period for doses greater
than 5mg/kg/day. Recommended concentration is 0.2mg/ml -
2.0mg/ml. Non-equivalence of amphotericin products: Different
amphotericin products (sodium deoxycholate, liposomal, lipid complex)
are not equivalent in terms of pharmacodynamics, pharmacokinetics
and dosing and so the products should not be used interchangeably
without accounting for these differences. Both the trade name,
common name and dose should be verified pre-administration. There
is a risk of under-dose if AmBisome is administered at a dose
recommended for amphotericin B deoxycholate. Posology -
Administration of a test dose is advisable before a new course of
treatment. A small amount of an AmBisome infusion (e.g. 1 mg) can be
administered for about 10 minutes and then stopped and the patient
observed carefully for the next 30 minutes. If there have been no
severe allergic or anaphylactic/anaphylactoid reactions the infusion of
AmBisome dose can be continued. Mycoses: Usually instituted at a
daily dose of 1.0mg/kg of body weight, and increased stepwise to
3.0mg/kg. Data presently insufficient to define total dosage
requirements and duration of treatment. However, a cumulative dose
of 1.0 – 3.0g over 3 – 4 weeks has been typical. Dosage must be
adjusted to the specific requirements of each patient. Mucormycosis:
Recommended starting dose is 5 mg/kg/daily. Duration determined on
an individual basis. Courses of up to 6-8 weeks are commonly used in
clinical practice. Longer durations may be required for deep seated
infections or during prolonged courses of chemotherapy or
neutropenia. Doses greater than 5 mg/kg and up to a maximum of 10
mg/kg have been used in clinical trials and clinical practice, however
data on safety and efficacy are limited. Therefore a benefit:risk
assessment should be made to determine whether the potential
benefits are considered to outweigh known risks of toxicity at these
higher doses. Visceral leishmaniasis: Total dose of 21.0 – 30.0 mg/kg
of body weight over 10-21 days. Particulars as to the optimal dosage
and eventual development of resistance yet incomplete. To be
administered under strict medical supervision. Empirical treatment of
febrile neutropenia: Recommended dose is 3mg/kg body weight per
day. Treatment should be continued until recorded temperature is
normalised for 3 consecutive days. Treatment should be discontinued
after maximum of 42 days. Special populations/Dose Adjustments:
Children <1 month: Not recommended due to lack of data on safety
and efficacy. Elderly: No dose adjustment. Renal Impairment: No dose
adjustment unless clinically significant reduction in renal function where
consideration should be given to dose reduction, treatment interruption or
discontinuation. Hepatic Impairment: No data available, no dose
recommendation.
CONTRAINDICATIONS: Hypersensitivity to active substance/any of
the excipients, unless the condition requiring treatment is life
threatening and amenable only to AmBisome therapy.
WARNINGS/PRECAUTIONS: Anaphylactic/anaphylactoid or severe
allergic reactions: Administration of a test dose is advisable. If severe
reaction occurs, infusion should be immediately stopped and the patient
should not receive any further infusion. Infusion related-reaction:
Precautionary measures are advisable. Slower infusion rates of over 2
hours or routine administration of diphenhydramine, paracetamol,
pethidine and/or hydrocortisone have been reported to be successful
in their prevention or treatment. Renal toxicity: Caution advised for
prolonged therapy. Laboratory evaluation of serum electrolytes,
particularly potassium and magnesium, as well as renal, hepatic and
haematopoietic function should be performed at least weekly, and
particular attention should be given to patients receiving concomitant
