PRESENTATION: A sterile powder for concentrate for dispersion for infusion. Each vial contains 50mg of amphotericin B (50,000 units), encapsulated in liposomes. Each vial contains 213 mg of hydrogenated soy phosphatidylcholine, 900 mg of sucrose and a small amount of sodium.
INDICATIONS (adults and children aged 1 month to 18 years): 1) Systemic mycotic infections due to organisms susceptible to this anti-infective, such as cryptococcosis, North American blastomycosis, disseminated candidiasis, coccidioidomycosis, aspergillosis, histoplasmosis, mucormycosis and in the treatment of some cases of American mucocutaneous leishmaniasis. 2) Treatment of fever of unknown origin in neutropenic patients, defined as persisting fever, unresponsive to as least 96 hours of antibiotic treatment. 3) Primary therapy of visceral leishmaniasis in both immunocompetent and immunocompromised (e.g. HIV positive) patients. 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: Dosage must be adjusted to the specific requirements of each patient. Preparation: Follow reconstitution instructions exactly as given in the SmPC. Administration: A test dose (1 mg) should be infused slowly for up to 10 mins and the patient carefully observed for 30 mins afterwards. AmBisome should be administered by intravenous infusion over a 30 - 60 mins period or over a 2 hour period for doses greater than 5 mg/kg/day. The recommended final concentration is 0.2 mg/ml - 2.0 mg/ml. Posology: Systemic mycotic infections: Therapy is usually instituted at a daily dose of 1.0 mg/kg of body weight, and increased stepwise to 3.0 mg/kg. A cumulative dose of 1.0 – 3.0g over 3 – 4 weeks has been typical. Mucormycosis: Initiate treatment with 5 mg/kg/daily. Duration of therapy should be determined on an individual basis. Courses of up to 56 days are commonly used in clinical practice. Longer durations may be required for deep seated infections or prolonged courses of chemotherapy or neutropenia. Doses greater than 5 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 on an individual patient level to determine whether the potential benefits are considered to overweigh known risks of toxicity at these higher doses. Fever of unknown origin in neutropenic patients: Therapy should be initiated at 1.0 mg/kg/day and may be raised to 3 mg/kg/day if indicated. Visceral leishmaniasis: Dose of 1.0 - 1.5 mg/kg/day for 21 days or alternatively, a dose of 3.0 mg/kg/day for 10 days, can be used. 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 ingredient/any of the excipients unless the condition requiring treatment is life threatening and amenable only to AmBisome therapy. AmBisome contains soya oil. If you are allergic to peanut or soya, do not use this medicinal product.
WARNINGS/PRECAUTIONS: Anaphylaxis and anaphylactoid reactions: Test dose should be administered initially to detect idiosyncratic anaphylactic reactions and minimise the dose administered if a reaction occurs. If severe reaction occurs, infusion should be immediately stopped and patient should not receive any further infusion. Infusion-related reactions: 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 effects: Laboratory evaluation of serum potassium and magnesium levels and renal, hepatic and haematopoietic function should be performed, particularly in patients receiving concomitant nephrotoxic drugs. Refer to SmPC for full information on interactions with other medicines. Potassium supplementation may also be required. If renal function deteriorates significantly, consideration should be given to dosage reduction, treatment interruption or discontinuation. Pulmonary Effects: Acute pulmonary toxicity has been reported in patients given amphotericin B (as sodium deoxycholate complex) during or shortly after leukocyte transfusions. It is recommended that infusions are separated by as long a period as possible and pulmonary function should be monitored. Diabetic patients: Each vial contains approximately 900mg of sucrose. Renal dialysis patients: No dose adjustment is required, however administration should be avoided during

haemodialysis or filtration procedures. AmBisome should not be administered to patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomeltase insufficiency. AmBisome contains less than 1 mmol sodium (23 mg) per vial.
INTERACTIONS: No interaction studies have been performed with AmBisome, however some medicinal products known to interact with amphotericin B may interact with AmBisome. See SmPC for full list.
PREGNANCY/LACTATION: Safety not established, the risk/benefit assessment should be considered.
DRIVING/USING MACHINERY: No studies have been performed. Some side effects of AmBisome may impact the ability to drive and use machines.
SIDE EFFECTS: Refer to SmPC for full information on side effects. Very common ≥ 1/10): hypokalaemia, nausea, vomiting, pyrexia, rigors. Common (≥ 1/100 to < 1/10): hypomagnesaemia, hypocalcaemia, hyperglycaemia, hyponatraemia, headache, tachycardia*, vasodilation, flushing*, hypotension*, dyspnoea*, diarrhoea, abdominal pain, liver function tests abnormal, hyperbilirubinaemia, alkaline phosphatase increased, rash, back pain*, increased creatinine, blood urea increased, chest pain*. Uncommon (≥ 1/1,000 to < 1/100): thrombocytopenia, anaphylactoid reaction, convulsion, bronchospasm*, phlebitis. Unknown frequency: anaemia, anaphylactic reactions, hypersensitivity, cardiac arrest, arrhythmia, angioneurotic oedema, rhabdomyolysis, renal failure, renal insufficiency, musculoskeletal pain* (described as arthralgia, back pain or bone pain). Chest tightness and the side effects marked * may be infusion-related reactions and these resolve rapidly when stopping the infusion. False elevations of serum phosphate may occur when samples from patients receiving AmBisome are analysed using the PHOSm assay. In two double-blind studies, the incidence of nephrotoxicity with AmBisome is approximately half of that reported for conventional amphotericin B or amphotericin B lipid complex.
OVERDOSE: Stop administration immediately and carefully monitor serum electrolytes, hepatic, renal and haematopoietic function. PHARMACEUTICAL PRECAUTIONS: Do not store above 25°C. AmBisome is a single dose unpreserved sterile lyophile, the reconstituted and diluted product should be used immediately. In-use storage not normally longer than 24 hours at 2 - 8°C, unless reconstitution and dilution has taken place in controlled and validated aseptic conditions. Chemical and physical stability has been demonstrated for 24 hours at 25 ± 2°C and 7 days at 2 - 8°C for reconstituted product. Following dilution with 5% dextrose, stability has been shown for 24 hours at 25 ± 2°C and 4 days at 2 - 8°C. Following dilution with 10% or 20% dextrose, stability has been shown for 72 hours at 25 ± 2°C and 48 hours at 2 - 8 °C. DO NOT STORE partially used vials for future patient use. Single use only and any unused contents should be discarded. DO NOT RECONSTITUTE AMBISOME WITH SALINE, OR MIX WITH MEDICINAL PRODUCTS OTHER THAN THOSE SPECIFIED IN THE SmPC. AmBisome is not interchangeable with other amphotericin B products.
LEGAL CATEGORY: POM. Rx1. PACK: Carton of 10 vials. PRICE: POA.
MARKETING AUTHORISATION NUMBER: PA 2322/001/001.
FURTHER INFORMATION: Gilead Sciences Ltd, 280 High Holborn, London, WC1V 7EE, UK. Tel: +353 214 825 999, e-mail: ukmedinfo@gilead.com. AmBisome is a trademark.
DATE OF PREPARATION: October 2020. UK-ANF-2020-09-0037