Presentation and Status in Health Basket
10 X 50 mg/vial
AmBisome should be administered by intravenous infusion over a 30 – 60 minute period. For doses greater than 5 mg/kg/day, intravenous infusion over a 2 hour period is recommended. The recommended concentration for intravenous infusion is 0.20 mg/ml to 2.00 mg/ml amphotericin B as AmBisome.
Treatment of systemic mycoses and visceral leishmaniasis: Therapy is usually instituted at a daily dose of 1.0 mg/kg of body weight, and increased stepwise to 3.0 mg/kg, as required. Dosage of amphotericin B as AmBisome must be adjusted to the specific requirements of each patient. A cumulative dose 1.0 – 3.0 g of AmBisome over 3-4 weeks has been typical of the treatment necessary for the resolution of mycoses.
Empirical treatment of febrile neutropenia: The recommended daily dose is 3 mg/kg body weight per day. Treatment should be continued until the recorded temperature is normalised for 3 consecutive days. In any event, treatment should be discontinued after a maximum of 42 days.
Paediatric Patients: Systemic fungal infections and visceral leishmaniasis in children1, 2 and presumed fungal infections in children with febrile neutropenia have been successfully treated with AmBisome without reports of unusual adverse events. AmBisome has been studied in paediatric patients aged one month to 18 years old. Dosage should be calculated on the same per-Kg body weight basis as for adults.
The safety and efficacy of AmBisome has not been established in infants under one month old.
Elderly Patients: No alteration in dose or frequency of dosing is required.
Renal Impairment: AmBisome has been administered to patients with pre-existing renal impairment at doses of 1-5 mg/kg/day in clinical trials and no adjustment in dose or frequency of administration was required.
Hepatic Impairment: No data are available on which to make a dose recommendation for patients with hepatic impairment.
In the treatment of severe systemic and/or deep mycoses where toxicity (particularly nephrotoxicity) precludes the use of conventional systemic amphotericin B in effective dosages.
This drug should not be used to treat the common clinically inapparent forms of fungal disease which show only positive skin or serologic tests.
In the treatment of systemic fungal infections in immuno-compromised patients (e.g. patients with AIDS or Cancer).
As the primary therapy of visceral leishmaniasis in immunocompetent patients and immunocompromised patients (e.g. HIV Positive).
In the empirical treatment of presumed fungal infection in febrile neutropenic patients.
Hypersensitivity to any of the product ingredients unless, in the opinion of the physician, the condition requiring treatment is life threatening and amenable only to AmBisome therapy.
Anaphylaxis and anaphylactoid reactions have been reported in association with AmBisome infusion. If a severe anaphylactic/anaphylactoid reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusion of AmBisome.
Other severe infusion-related reactions can occur during administration of amphotericin B-containing products, including AmBisome. Although infusion-related reactions are not usually serious, consideration of precautionary measures for the prevention or treatment of these reactions should be given to patients who receive AmBisome therapy. Slower infusion rates (over 2 hours) or routine doses of diphenhydramine, paracetamol, pethidine, and/or hydrocortisone have been reported as successful in its prevention or treatment.
AmBisome has been shown to be substantially less toxic than conventional amphotericin B particularly with respect to nephrotoxicity; however, adverse reactions including renal adverse reactions may still occur.
In studies comparing AmBisome 3 mg/kg daily with higher doses (5,6 or 10 mg/kg daily), it was found that the incidence rates of increased serum creatinine, hypokalemia and hypomagnesaemia were notably higher in the high dose groups.
Regular laboratory evaluation of serum electrolytes, particularly potassium and magnesium, as well as renal, hepatic and haematopoietic function should be performed. This is particularly important in patients receiving concomitant nephrotoxic medications. Due to the risk of hypokalaemia, appropriate potassium supplementation may be required during the course of AmBisome administration. If clinically significant reduction in renal function or worsening of other parameters occurs, consideration should be given to dose reduction, treatment interruption or discontinuation.
Acute pulmonary toxicity has been reported in patients given amphotericin B (as sodium deoxycholate complex) during or shortly after leukocyte transfusions. It is recommended these infusions are separated by as long a period as possible and pulmonary function should be monitored.
In the Treatment of Diabetic Patients: It should be noted that AmBisome contains approximately 900 mg of sucrose in each vial.
Fever and chills/rigors are the most frequent infusion-related reactions expected to occur during AmBisome administration.
Less frequent infusion-related reactions may consist of one or more of the following symptoms: chest tightness or pain, dyspnoea, bronchospasm, flushing, tachycardia hypotension and musculoskeletal pain (described as arthralgia, back pain, or bone pain). These resolved rapidly on stopping the infusion and may not occur with every subsequent dose or when slower infusion rates (over 2 hours) are used.
In addition, infusion-related reactions may also be prevented by the use of premedication. However, severe infusion-related reactions may necessitate the permanent discontinuation of AmBisome.
See prescribing information for full details.
No specific interaction studies have been performed with AmBisome. However, the following drugs are known to interact with amphotericin B and may interact with AmBisome:
Nephrotoxic medications: Concurrent administration of amphotericin B with other nephrotoxic agents (for example, ciclosporin, aminoglycosides and pentamidine) may enhance the potential for drug-induced renal toxicity in some patients. However, in patients receiving concomitant ciclosporin and/or aminoglycosides, AmBisome was associated with significantly less nephrotoxicity compared to amphotericin B.
Regular monitoring of renal function is recommended in patients receiving AmBisome with any nephrotoxic medications.
Corticosteroids, corticotropin (ACTH) and diuretics: Concurrent use of corticosteroids, ACTH and diuretics (loop and thiazide) may potentiate hypokalemia.
Digitalis glycosides: AmBisome-induced hypokalemia may potentiate digitalis toxicity.
Skeletal muscle relaxants: AmBisome-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g. tubocurarine).
Antifungals: Concurrent use with flucytosine may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion.
Antineoplastic agents: Concurrent use of antineoplastic agents may enhance the potential for renal toxicity, bronchospasm and hypotension. Antineoplastic agents should be given concomitantly with caution.
Leukocyte transfusions: Acute pulmonary toxicity has been reported in patients given amphotericin B (as sodium deoxycholate complex) during or shortly after leukocyte transfusions. It is recommended these infusions are separated by as long a period as possible and pulmonary function should be monitored.
Pregnancy and Lactation
Pregnancy: The safety of AmBisome in pregnant women has not been established. AmBisome should only be used during pregnancy if the possible benefits to be derived outweigh the potential risks to the mother and foetus.
Lactation: It is unknown if AmBisome is excreted in human milk.
A decision on whether to breastfeed while receiving AmBisome should take into account the potential risk to the child as well as the benefits of breast feeding for the child and the benefit of AmBisome therapy for the mother.
See prescribing information for full details.
The toxicity of AmBisome due to acute overdose has not been defined. If overdose should occur, cease administration immediately. Carefully monitor clinical status including renal and hepatic function, serum electrolytes and haematologic status. Haemodialysis or peritoneal dialysis does not appear to affect the elimination of AmBisome.
Incompatibilities: AmBisome is not physically compatible with saline solutions and should not be mixed with other drugs or electrolytes.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6 at the attached doctor’s leaflet.