What it is and what it is used for

for The name of your medicine is Fungizone 50mg Powder for Sterile Concentrate. It contains the active ingredient amphotericin B, which belongs to a group of medicines called anti-fungal antibiotics. Fungizone 50mg Powder for Sterile Concentrate is used to treat serious infections caused by yeasts and certain fungi.

What you need to know before you take it

your medicine You should not be given this medicine if you:

• are allergic (hypersensitive) to amphotericin or any of the other ingredients in this medicine. Take special care with Fungizone 50mg Powder for Sterile Concentrate if you: – have any kidney or liver problems If this applies to you, talk to your doctor before being given Fungizone 50mg Powder for Sterile Concentrate. Taking other medicines Always tell your doctor or pharmacist about other medicines you may be taking or have recently taken including those obtained without a prescription. This is especially important if you are taking: any anti-cancer medicines (e.g. methotrexate, cyclophosphamide, cisplatin) – any medicines which affect your kidney function (e.g. gentamicin, vancomycin) – any muscle relaxants (e.g. baclofen, dantrolene, diazepam) – any corticosteroids (e.g. beclamethasone) or corticotrophins – any medicines to treat heart failure (e.g. digoxin) – a medicine called flucytosine used to treat fungal infections –

If you have recently had a specific type of transfusion called a leukocyte transfusion, please tell your doctor. Pregnancy and breast-feeding If you are pregnant, think you may be pregnant, or if you are breast-feeding, speak to your doctor before being given Fungizone 50mg Powder for Sterile Concentrate. Driving and using machinery Fungizone 50mg Powder for Sterile Concentrate should not affect your ability to drive. Fungizone contains amphotericin B: This medicinal product also contains less than 1mmol sodium (23mg) per dose, i.e. essentially 'sodiumfree'.

How to take it

your medicine Fungizone 50mg Powder for Sterile Concentrate will be given to you in hospital by a doctor or nurse. The daily dose is 0.25-1.0 mg per kg of your body weight. In some cases your doctor may consider it necessary to increase this dose to 1.5 mg/kg. If you are given too much of this medicine, you may experience life-threatening heart or lung problems. If you have any concerns about the amount of medicine you have been given, please speak to the person who has given you the infusion for further advice. It will be given to you slowly through a drip into a vein (an infusion). This will usually take between 2-6 hours. A test dose may be given before you start treatment with this medicine. Several months of treatment is usually necessary to get rid of the infection completely. In some patients, the doctor may give other medicines to help reduce other unwanted effects. These include: medicines to help stop you feeling sick or being sick, aspirin, an anti-allergy medicine (antihistamine), a corticosteroid, a medicine to stop your blood from clotting (anticoagulant).

Possible side effects

Like all medicines, Fungizone 50mg Powder for Sterile Concentrate can cause side effects, although not everybody gets them. Treatment with Fungizone 50mg Powder for Sterile Concentrate may affect your blood cells, kidneys, liver or heart. For this reason, your doctor will want to monitor all these things before, during and after giving you this medicine. If you notice any of the following, contact your doctor immediately: swelling of the face, lips, or tongue

• skin reactions including severe rash and itching
• difficulty breathing As these may be signs of an allergic reaction. –

There have been reports of blood disorders which may be characterised by fever or chills, sore throat, ulcers in the mouth or throat, unusual tiredness or weakness, unusual bleeding or unexplained bruises. Tell your doctor immediately if you notice any of these symptoms. Fungizone 50mg Powder for Sterile Concentrate can cause kidney problems. If you notice that you are more thirsty, need to go to the toilet more frequently, or the volume of urine increases, tell your doctor immediately. Patients treated with Fungizone have reported the following side effects: Very common: may affect more than 1 in 10 people • Feeling sick and being sick • High temperature (sometimes with shaking chills) • Decrease in potassium in the blood • Increase in creatinine in the blood • Kidney problems which may lead to abnormal urine production, kidney stones and imbalances of substances in the blood (e.g. potassium) • Difficulty in breathing • Low blood pressure Common: may affect up to 1 in 10 people • Anaemia-low level of red blood cells • Abnormal liver function shown by abnormal liver function tests • Decreased magnesium in the blood • Headache • Diarrhoea • Rash • Decreased appetite • Sudden loss of kidney function • Pain at the injection site with or without swollen veins or a blood clot

Uncommon: may affect up to 1 in 100 people • A rare form of anaemia where there is a low level of white blood cells • Low counts of white blood cells in the blood • Low counts of platelets in the blood • Irregular heartbeat, sometime severe • Impaired sensation or movement • Spasm of the lungs • Pain in the stomach • Yellowing of the skin and eyes • Pain in muscles • Impaired or abnormal kidney function • Flushing Rare: may affect up to 1 in 1,000 people • Abnormal blood clotting • High counts of white blood cells in the blood • Allergic reaction • Increased potassium in the blood • Altered mental state • Convulsion • Vision blurred or double vision • Hearing loss, ringing in the ears • Short-lived spinning sensation (vertigo) • Heart attack or heart not working properly • High blood pressure • Shock • Inflammation of the lungs and fluid in the lungs • Stomach cramps, indigestion • Bleeding in intestines, resulting in black faeces • Loss of liver function • Rash- characterized by a flat red area on the skin that is covered with small bumps • Itching • Flu like symptoms followed by a painful red or purple spreading rash • Skin conditions including skin coming off in layers • Pain in joints • Abnormal kidney function including increased or decreased amounts of urine produced • Pain and tiredness • Decreased weight Reporting of side effects If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects, you can help provide more information on the safety of this medicine.

How to store it

your medicine Keep this medicine out of the sight and reach of children. Unopened product will be stored in a refrigerator (2-8°C) in the pharmacy and should not be used after the expiry date shown on the carton/label. This medicine will be prepared in a special area before the doctor or nurse gives it to you. After being mixed together the medicine will be kept for no more than 8 hours at room temperature (25°C) or 24 hours in a refrigerator (2-8°C). It should be stored protected from light.

Contents of the pack and other information

What Fungizone 50mg Powder for Sterile Concentrate contains The active substance is amphotericin B. Each vial contains 50mg (50,000 units) Amphotericin B. The other ingredients are desoxycholic acid, concentrated phosphoric acid, sodium hydroxide, disodium phosphate dodecahydrate, monosodium phosphate dehydrate, water.

What Fungizone 50mg Powder for Sterile Concentrate looks like and contents of the pack Fungizone 50mg Powder for Sterile Concentrate is a fine yellow to orange, fluffy powder and is supplied in glass vials.

Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder: Neon Healthcare Limited 8 The Chase, John Tate Road, Hertford, SG13 7NN United Kingdom Manufacturer Delpharm Saint Remy Usine de Saint-Remy Rue de I'Isle 28380 Saint-Remy-Sur-Avre France This leaflet was last revised in September 2021. ——————————————————————————————————————————–PLEASE DETACH BEFORE HANDING ABOVE SECTION TO THE PATIENT INFORMATION FOR HEALTH PROFESSIONALS Below is a summary of the dosage, administration, reconstitution and storage details for Fungizone 50mg Powder for Sterile Concentrate. Reference should be made to the Summary of Product Characteristics for full prescribing information. ADMINISTRATION Posology Fungizone should be administered by intravenous infusion over a period of 2-6 hours. Reduction of the infusion rate may reduce the incidence of side effects. Initial daily dose should be 0.25 mg/kg of body weight gradually increasing to a level of 1.0 mg/kg of body weight depending on individual response and tolerance. Within the range of 0.25-1.0 mg/kg the daily dose should be maintained at the highest level which is not accompanied by unacceptable toxicity. In seriously ill patients the daily dose may be gradually increased up to a total of 1.5 mg/kg. Since amphotericin B is excreted slowly, therapy may be given on alternate days in patients on the higher dosage schedule. Several months of therapy are usually necessary; a shorter period of therapy may produce an inadequate response and lead to relapse. When commencing all new courses of treatment, it is advisable to administer a test dose immediately preceding the first dose. A volume of the infusion containing 1mg (i.e. 10mL) should be infused over 20-30 minutes and the patient carefully observed for at least a further 30 minutes. It should be noted that patient responses to the test dose may not be predictive of subsequent severe side effects. Patients with a severe and rapidly progressing fungal infection, with good cardiopulmonary function and who tolerates the test dose without a severe reaction, may then receive 0.3 mg/kg amphotericin B intravenously over a period of 2 to 6 hours. For patients with cardiopulmonary impairment or severe reaction to the test dose, a lower dose (i.e. 5 to 10 mg) is recommended. Doses may gradually be increased by 5 to 10 mg per day to a final daily dosage of 0.5 to 1 mg/kg Whenever medication is interrupted for a period longer than seven days, therapy should be resumed by starting with the lowest dosage level, i.e. 0.25 mg/kg of body weight and increased gradually. CAUTION: Under no circumstances should a total daily dose of 1.5 mg/kg be exceeded. The recommended concentration for intravenous infusion is 10 mg/100 mL. Paediatric population

Safety and effectiveness in paediatric patients have not been established through adequate and wellcontrolled studies. Systemic fungal infections have been treated in paediatric patients, with reports of side effects similar to those seen in adults. Older people No specific dosage recommendations or precautions. RECONSTITUTION: Reconstitute as follows: An initial concentrate of 5 mg amphotericin B per ml is first prepared by rapidly expressing 10ml sterile water for injection, without a bacteriostatic agent, directly into the lyophilized cake, using a sterile needle (minimum diameter: 20 gauge) and syringe. Shake the vial immediately until the colloidal solution is clear. The infusion solution, providing 10mg/100mL is obtained by further dilution (1:50) with 5% Glucose Injection of pH above 4.2. The pH of each container of Glucose Injection should be ascertained before use. Commercial Glucose Injection usually has a pH above 4.2; however, if it is below 4.2 then 1 or 2 ml of buffer should be added to the Glucose Injection before it is used to dilute a concentrated solution of amphotericin. The recommended buffer has the following composition: Dibasic sodium phosphate (anhydrous) 1.59 g Monobasic sodium phosphate (anhydrous) 0.96 g Water for Injections BP q.s. to 100 mL The buffer should be sterilised before it is added to the Glucose Injection, either by filtration through a bacterial filter, or by autoclaving for 30 mins at 15 lb pressure (121°C). CAUTION: Aseptic technique must be strictly observed in all handling, since no preservative or bacteriostatic agent is present. Do not use the initial concentrate or the infusion solution if there is any evidence of precipitation of foreign matter. An in-line membrane filter may be used for intravenous infusion of amphotericin B; however the mean pore diameter of the filter should not be less than 1.0 micron in order to assure passage of the amphotericin dispersion. Other preparations for injection should not be added to the infusion solution or administered via the cannula being used to administer Fungizone. Aseptic technique must be strictly observed during the preparation of the concentrate, the buffer and the infusion. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. The use of Fungizone by other routes has been documented in the published literature: Bladder irrigation/instillation (eg candiduria): Continuous irrigation with 50mg Fungizone in 1 litre sterile water each day until urinary cultures are negative. Intermittent use of volumes of 100-400mL (concentrations of 37.5-200 mcg/mL) has also been reported. The urine should be alkalinized (with potassium citrate) and antifungal ointment applied to the perineal area. Lung inhalation (eg pulmonary aspergillosis): 8-40 mg amphotericin B (nebulized in sterile water or 5% Glucose) has been given daily in divided doses. Concurrent eradication of oral and intestinal yeast reservoirs is recommended. Intrathecal (eg coccidiodal meningitis): Patients who do not respond to fluconazole or itraconazole would be candidates for intrathecal amphotericin B therapy with or without continuation of azole treatment. The intrathecal dosage of amphotericin B normally ranges between 0.1mg and 1.5mg per dose, administered at intervals ranging from daily to weekly, beginning at a low dosage and increasing the dosage until the appearance of patient intolerance. Amphotericin B is irritating when injected into the CSF. Reports of neurological events such as arachnoiditis, myelopathy, paresis and paralysis have been associated with the intrathecal route of administration.

Other: Other uses of solutions prepared using Fungizone include local instillations for the treatment of fungal infections of the ear, eye, peritoneum, lung cavities and joint spaces. SPECIAL PRECAUTIONS FOR STORAGE Vials of powder for reconstitution should be stored in a refrigerator Reconstituted: After reconstitution with 10 mL sterile Water for Injections the concentrate (5 mg/ml) should be stored protected from light. The absence of any antimicrobial preservative and the risk of contamination during reconstitution mean that the product should be stored for no more than 8 hours at room temperature (25°C) or 24 hours in a refrigerator (2-8°C). Should the need arise and a validated aseptic reconstitution technique is applied, the product is chemically stable when stored for 24 hours at room temperature or one week in a refrigerator. It is not intended as a multidose vial. Any unused material should be discarded. Solutions prepared for intravenous infusion (i.e. 10 mg or less amphotericin B per 100 mL) should be used promptly after preparation.