BIAMSUN LIPOSOMAL

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 BIAMSUN liposomal is administered at a dose recommended for amphotericin B deoxycholate. 4). Treatment of mycoses Therapy is usually instituted at a daily dose of 3 to 5 mg/kg of body weight for a minimum of 14 days..

Dosage of amphotericin B as BIAMSUN liposomal must be adjusted to the specific requirements of each patient. Mucormycosis For suspected or confirmed infection, the recommended starting dose is 5 to 10 mg/kg/day. In patients with brain involvement or solid-organ transplant, dose at 10 mg/kg/day.

Avoid slow escalation of doses. The duration of therapy should be determined on an individual basis. Courses of up to 6 – 8 weeks are commonly used in clinical practice; longer durations of therapy may be required for deep seated infections or in cases of prolonged courses of chemotherapy or neutropenia.

Although doses greater than 5 mg/kg and up to a maximum of 10 mg/kg have been used in clinical trials and clinical practice, data on the safety and efficacy of BIAMSUN liposomal for the treatment of mucormycosis at these higher doses are limited.

4). HIV associated Cryptococcal meningitis Administer a single dose of 10 mg/kg Amphotericin B SUN Pharma liposomal on day 1, in combination with daily flucytosine 100 mg/kg and daily fluconazole 1200 mg, both administered for 14 days.

After the 2-week induction period, patients should receive fluconazole 800 mg daily for 8 weeks and then at a dose of 200 mg daily thereafter at the treating physician's discretion. 0 mg/kg of body weight given over 10-21 days may be used in the treatment of visceral leishmaniasis.

Particulars as to the optimal dosage and the eventual development of resistance are as yet incomplete. The product should be administered under strict medical supervision. Empirical treatment of febrile neutropenia The recommended daily dose is 3 to 5 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 population Both systemic fungal infections in children and presumed fungal infections in children with febrile neutropenia have been successfully treated with BIAMSUN liposomal, without reports of unusual adverse events.

BIAMSUN liposomal has been studied in paediatric patients aged one month to 18 years old. Doses used in these clinical studies were the same as those used in adults on a mg/kg body weight basis. BIAMSUN liposomal is not recommended for use in children below 1 month old due to lack of data on safety and efficacy.

Elderly patients No alteration in dose or frequency of dosing is required. 4). 4). Method of administration BIAMSUN liposomal should be administered by intravenous infusion over a 30 - 60 minute period and the patient closely observed.

4). 00 mg/ml amphotericin B as BIAMSUN liposomal. 6.

Summary of adverse reactions The following adverse reactions have been attributed to BIAMSUN liposomal based on clinical trial data and post-marketing experience. The frequency is based on analysis from pooled clinical trials of 688 BIAMSUN liposomal treated patients; the frequency of adverse reactions identified from post- marketing experience is not known.

Adverse reactions are listed below by body system organ class using MedDRA and are sorted by frequency. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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) 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, hyperkalaemia 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: abnormal liver function tests, hyperbilirubinaemia, increased alkaline phosphatase Skin and subcutaneous disorders Common: rash Not known: angioneurotic oedema Musculoskeletal and connective tissue disorders Common: back pain Not Known: rhabdomyolysis (associated with hypokalaemia), musculoskeletal pain (described as arthralgia or bone pain) Renal and urinary disorders Common: increased creatinine, increased blood urea Not known: renal failure, renal insufficiency General disorders and administration site conditions Very Common: rigors, pyrexia, Common: chest pain Description of selected adverse reactions Infusion-related reactions Fever and chills/rigors are the most frequent infusion-related reactions expected to occur during BIAMSUN liposomal 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.

4). In two double-blind, comparative studies, BIAMSUN liposomal 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 Amphotericin B liposomal with conventional amphotericin B therapy in greater than 1,000 patients, reported adverse reactions were considerably less severe and less frequent in BIAMSUN liposomal treated patients as compared with conventional amphotericin B treated patients.

A randomized phase III study assessed a single 10 mg/kg dose of Amphotericin B SUN Pharma liposomal with a backbone of 14 days flucytosine and fluconazole, compared to the control group (1-week conventional amphotericin B plus flucytosine followed by 1 week of fluconazole) in the treatment of HIV associated cryptococcal meningitis.

The Amphotericin B SUN Pharma liposomal treated patients experienced fewer grade 3 or 4 adverse events compared to the control group. The safety profile observed in this patient population was consistent with the overall safety profile for Amphotericin B SUN Pharma liposomal.

Renal toxicity Nephrotoxicity occurs to some degree with conventional amphotericin B in most patients receiving the product intravenously. 0 times baseline measurement), was approximately half that for conventional amphotericin B. 0 times baseline measurement) was approximately half that for Amphotericin B lipid complex.

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. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Anaphylaxis and anaphylactoid reactions Anaphylaxis and anaphylactoid reactions have been reported in association with BIAMSUN liposomal infusion. 8). Therefore, every dose of Amphotericin B SUN Pharma liposomal should be infused over 30-60 minutes and the patient closely monitored every time.

If a severe allergic or anaphylactic/anaphylactoid reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusion of Amphotericin B SUN Pharma liposomal. 8). 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 BIAMSUN liposomal therapy.

Slower infusion rates (over 2 hours) or routine doses of diphenhydramine, paracetamol, pethidine and/or hydrocortisone have been reported as successful in their prevention or treatment. Renal toxicity BIAMSUN liposomal has been shown to be substantially less toxic than conventional amphotericin B, particularly with respect to nephrotoxicity; however, renal adverse reactions may still occur.

In studies comparing BIAMSUN liposomal 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, hypokalaemia 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, at least once weekly. In particular, caution should be exercised when prolonged therapy is required.

Renal function should be closely monitored in these patients. Due to the risk of hypokalaemia, appropriate potassium supplementation may be required during the course of BIAMSUN liposomal 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.

Cases of hyperkalaemia (some of them leading to cardiac arrhythmias and cardiac arrest) have been reported. Most of them occurred in patients with renal impairment, and some cases after potassium supplementation in patients with previous hypokalaemia.

Therefore, renal function and laboratory evaluation of potassium, should be measured before and during treatment. 5). Pulmonary toxicity 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 these infusions are separated by as long a period as possible and pulmonary function should be monitored. Diabetic patients BIAMSUN liposomal contains approximately 900 mg of sucrose in each vial. This should be taken into account when treating diabetic patients.

e. essentially 'sodium free'.

1 unless, in the opinion of the physician, the condition requiring treatment is life- threatening and amenable only to BIAMSUN liposomal therapy.