AmBisome Adverse Reactions

Summary of adverse reactions: The following adverse reactions have been attributed to AmBisome, based on clinical trial data and post-marketing experience. The frequency is based on analysis from pooled clinical trials of 688 AmBisome treated patients: the frequency of adverse reactions identified from post-marketing experience is not known. Adverse reactions are listed as follows by body system organ class using MedDRA and are sorted by frequency.
Frequencies are defined as: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Blood and lymphatic system disorders: Uncommon: thrombocytopenia.
Not known: anaemia.
Immune system disorders: Uncommon: anaphylactoid reaction.
Not known: anaphylactic reactions, hypersensitivity.
Metabolism and nutrition disorders: Very common: hypokalaemia.
Common: hyponatraemia, hypocalcaemia, hypomagnesaemia, hyperglycaemia.
Nervous system disorders: Common: headache.
Uncommon: convulsion.
Cardiac disorders: Common: tachycardia.
Not known: cardiac arrest, arrhythmia.
Vascular disorders: Common: hypotension, vasodilatation, flushing.
Respiratory, thoracic and mediastinal disorders: Common: dyspnoea.
Uncommon: bronchospasm.
Gastrointestinal disorders: Very common: nausea, vomiting.
Common: diarrhoea, abdominal pain.
Hepatobiliary disorders: Common: liver function tests abnormal, hyperbilirubinaemia, alkaline phosphatase increased.
Skin and subcutaneous disorders: Common: rash.
Not known: angioneurotic oedema.
Musculoskeletal and connective tissue disorders: Common: back pain.
Not known: rhabdomyolysis (associated with hypokalemia), musculoskeletal pain (described as arthralgia or bone pain).
Renal and urinary disorders: Common: increased creatinine, blood urea increased.
Not known: renal failure, renal insufficiency.
General disorders and administration site conditions: Very common: rigors, pyrexia.
Common: chest pain.
Uncommon: phlebitis.
Description of selected adverse reactions: Infusion related reactions: 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 resolve 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 Precautions).
In two double-blind, comparative studies, AmBisome treated patients experienced a significantly lower incidence of infusion-related reactions, as compared to patients treated with conventional amphotericin B or amphotericin B lipid complex.
In pooled study data from randomised, controlled clinical trials comparing AmBisome with conventional amphotericin B therapy in greater than 1,000 patients, reported adverse reactions were considerably less severe and less frequent in AmBisome treated patients, as compared with conventional amphotericin B treated patients.
Renal effects: Nephrotoxicity occurs to some degree with conventional amphotericin B in most patients receiving the drug intravenously. In two, double-blind studies, the incidence of nephrotoxicity with AmBisome (as measured by serum creatinine increase greater than 2.0 times baseline measurement), is approximately half of that reported for conventional amphotericin B or amphotericin B lipid complex.
Interference with Phosphorus Chemistry Assays: False elevations of serum phosphate may occur when samples from patients receiving AmBisome are analyzed using the PHOSm assay (e.g. used in Beckman Coulter analyzers including the Synchron LX20). This assay is intended for the quantitative determination of inorganic phosphorus in human serum, plasma or urine samples.