Fungizone

Package leaflet: Information for the patient

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Fungizone (Fungizone ad Perfusionem), 50 mg, powder for solution for infusion
Amphotericin B
Fungizone and Fungizone ad Perfusionem are different trade names for the same medicinal product.
Please read this leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm others, even if their symptoms appear identical.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

1. What Fungizone is and what it is used for
2. What you need to know before receiving Fungizone
3. How to use Fungizone
4. Possible side effects
5. How to store Fungizone
6. Contents of the pack and other information

1. What Fungizone is and what it is used for

Fungizone is a powder for solution for infusion. The active substance in Fungizone is
amphotericin B, an antibiotic used to treat fungal infections.
Fungizone is used to treat patients with severe, potentially life-threatening fungal infections.

2. Information before using Fungizone

When not to use Fungizone:

• if the patient is allergic to amphotericin B or to any of the other ingredients of this medicine (listed in section 6), except in cases where the physician considers that a life-threatening condition has occurred and amphotericin B is the only possible treatment option.

Warnings and precautions
In life-threatening fungal infections, amphotericin B may be the only effective treatment available. The physician must individually weigh the benefits of life-saving therapy against the risks of unexpected and dangerous adverse reactions.
Amphotericin B should be administered only by trained medical personnel, intravenously, and exclusively to patients under strict specialist clinical supervision.
Acute reactions such as chills, fever, loss of appetite, nausea, vomiting, headache, muscle pain, joint pain, and hypotension commonly occur during intravenous administration of amphotericin B.
Rapid intravenous infusion given over less than 1 hour should be avoided, as it may lead to high blood potassium levels and cardiac arrhythmias, particularly in patients with renal impairment.
Leukoencephalopathy (brain white matter damage) has been observed in patients undergoing total body irradiation following treatment with amphotericin B.
During treatment, the physician may order laboratory tests and modify the treatment regimen based on test results.
Neurological adverse events (meningitis, spinal cord damage, paresis, paralysis) have been reported after administration of the drug into the space surrounding the spinal cord (intrathecally).

Fungizone with other medicines
Inform your doctor or nurse about all medicines currently used or recently used, as well as any medicines the patient plans to take.
Some medicines taken concomitantly with Fungizone may affect its action. This is particularly important if:

• the patient is taking any of the following medicines:
  • medicines that may damage the kidneys:
  • cisplatin (anticancer medicines),
  • cyclosporine (used after organ transplantation and in the treatment of autoimmune diseases),
  • aminoglycoside antibiotics (e.g. gentamicin, vancomycin),
  • pentamidine (an antiprotozoal medicine);
  • skeletal muscle relaxants (e.g. baclofen, diazepam);
  • corticosteroids (e.g. hydrocortisone) and corticotropin (ACTH);
  • cardiac glycosides (medicines used in heart failure treatment), e.g. digoxin;
  • medicines used to treat cardiac arrhythmias, e.g. quinidine;
  • flucytosine (a medicine used in the treatment of fungal infections);
• the patient has received white blood cells (leukocytes) by transfusion.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.

Pregnancy
This medicine may be used during pregnancy only with particular caution, if in the physician’s judgment the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding
It is not known whether amphotericin B passes into human milk. Breastfeeding mothers are advised to discontinue breastfeeding.

Driving and operating machinery
The effect of this medicine on the ability to drive and operate machinery has not been studied. The physician will advise the patient on the necessary precautions when performing these activities, as adverse reactions such as dizziness, visual disturbances, headache or other neurological symptoms, hypotension, and other severe adverse effects may occur during treatment, potentially impairing psycho-physical performance.

If the patient has any further questions about the use of Fungizone, he or she should consult the doctor or healthcare professional involved in the patient’s care.

Sodium content
The medicine contains less than 1 mmol (23 mg) of sodium per vial; therefore, it is considered "sodium-free".

Natural rubber (latex)
The medicine packaging contains latex rubber. It may cause severe allergic reactions.

3. How to use Fungizone

Fungizone is administered to the patient by a doctor or healthcare professional responsible for their care. If you have any doubts regarding the dose of the medicine received, please seek further information from the person administering the infusion.
The dosage of Fungizone is determined individually by the doctor, depending on the disease. The daily dose is 0.25–1.5 mg/kg body weight. The patient receives the medicine as a slow intravenous infusion (drip infusion into a vein via a cannula). This usually takes from 2 to 6 hours.
Before starting treatment, the patient may receive a small test dose of the medicine. Treatment usually lasts several months, until complete resolution of the infection.
Under no circumstances should the patient receive a daily dose exceeding 1.5 mg/kg body weight. Overdose of amphotericin B may cause cardiac arrest, respiratory arrest, or circulatory arrest, possibly resulting in death.
Use in children and adolescents
The safety and efficacy of amphotericin B have not been confirmed by adequate and well-controlled studies. During treatment of systemic fungal infections in children, no unusual adverse reactions have been reported.
Use of a higher than recommended dose of Fungizone
Under no circumstances should the total daily dose of 1.5 mg/kg body weight be exceeded. Use of a higher than recommended dose of Fungizone may cause cardiac arrest, circulatory arrest, or respiratory arrest, possibly resulting in death. If a higher than recommended dose of Fungizone has been administered, treatment should be discontinued and the patient's clinical condition should be monitored.
Missed dose of Fungizone
Do not administer a double dose to make up for a missed dose.
Discontinuation of Fungizone
If you have any further questions regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody will experience them.
Treatment with Fungizone may affect blood cells, kidneys, liver, and heart.
Therefore, your doctor will monitor their function before starting treatment, during treatment, and
after it has ended.
You must inform your doctor immediately if any of the following symptoms occur:

• swelling of the face, lips, or tongue,
• skin symptoms, such as severe rash, itching,
• difficulty breathing, as these symptoms may indicate a severe allergic reaction.

Blood system disorders have been reported in patients, presenting with fever or chills, sore throat,
ulceration of the oral or pharyngeal mucosa, fatigue or weakness, unusual bleeding, or unexplained
bruising. If you notice any of these symptoms, you must inform your doctor immediately.
Treatment with Fungizone may cause kidney damage. If you notice that you are more thirsty than
usual, need to urinate more frequently, or have increased urine output, you should contact your
doctor immediately.
The following are symptoms that may occur during treatment.
Very common (may affect more than 1 in 10 patients):

• nausea, vomiting
• fever, chills
• decreased potassium levels, increased creatinine levels in blood
• kidney function disorders
• shortness of breath
• low blood pressure.

Common (may affect up to 1 in 10 patients):

• anaemia
• liver function disorders
• decreased magnesium levels in blood
• rash.

Uncommon (may affect up to 1 in 100 patients):

• decreased or increased number of certain white blood cells (agranulocytosis, eosinophilia, leukocytosis, leukopenia)
• decreased platelet count
• blood coagulation disorders
• hot flushes.

Occurring with unknown frequency (frequency cannot be estimated from available data):

• heart rhythm disorders, cardiac arrest, heart failure
• hearing loss, tinnitus
• dizziness
• double or blurred vision
• indigestion, acute abdominal pain (cramps), gastrointestinal inflammation with bleeding
• diarrhoea
• black stools (blood in faeces)
• pain, malaise
• pain at the injection site, with or without phlebitis or thrombophlebitis
• acute liver failure, jaundice
• anaphylactic reactions and other allergic reactions
• increased potassium levels in blood
• weight loss
• loss of appetite
• joint pain, muscle pain
• seizures, headache, brain damage (encephalopathy) and other neurological disorders, peripheral nerve damage (neuropathy)
• kidney function disorders of varying severity, acute kidney failure
• allergic pneumonia, bronchospasm, pulmonary oedema
• severe allergic skin reactions, with blistering, peeling, and itching
• high blood pressure, shock.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 4921 301, fax: +48 22 4921 309, website: https://smz.ezdrowie.gov.pl
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store the medicine Fungizone

Keep the medicine out of the sight and reach of children.
Store in the original packaging to protect from light.
Store in a refrigerator (2°C-8°C).
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via sewage systems or household waste. Ask your pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the package and other information

What Fungizone contains

• The active substance is amphotericin B. One vial contains 50 mg of amphotericin B.
• The other components are disodium dihydrogen phosphate dihydrate, disodium phosphate dodecahydrate, deoxycholic acid, sodium hydroxide (for pH adjustment), phosphoric acid (for pH adjustment).

What Fungizone looks like and contents of the pack
Yellow to orange-yellow lyophilized powder.
Vial in a cardboard carton. The package contains 1 vial with 50 mg of amphotericin B.

For further information, please contact the marketing authorisation holder or the parallel importer.

Marketing Authorisation Holder in the Netherlands, country of export:
CHEPLAPHARM Arzneimittel GmbH
Ziegelhof 24
17489 Greifswald
Germany

Manufacturer:
Delpharm Saint Remy
Usine de Saint Rémy-rue de l’Isle
28380 Saint-Rémy-sur-Avre
France

Parallel importer:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Poland

Repackaged in:
Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111
91-222 Łódź
Poland

Marketing Authorisation Number in the Netherlands, country of export: RVG 01585
Parallel Import Authorisation Number: 35/26

Information intended exclusively for medical professionals

Preparation of the concentrate
To prepare a 5 mg/mL amphotericin B concentrate, rapidly inject 10 mL of sterile water for injection without bacteriostatic agent directly into the vial containing the lyophilized powder using a sterile syringe and needle (minimum gauge: 20 G). Immediately begin shaking the vial to obtain a clear colloidal dispersion.

Preparation of the infusion solution
To prepare the infusion solution, withdraw the appropriate amount of concentrate and dilute it with 5% dextrose solution so that the final concentration of amphotericin B is 0.1 mg/mL. Before using the dextrose solution, check its pH, which should be above 4.2. Commercially available dextrose solutions usually have a pH above 4.2; however, if the pH is below 4.2, add 1 or 2 mL of buffer to the dextrose solution before using it to dilute the amphotericin B solution. The composition of the recommended buffer is as follows:
Disodium hydrogen phosphate (anhydrous) 1.59 g
Sodium dihydrogen phosphate (anhydrous) 0.96 g
Water for injection qs ad 100 mL

Before adding the buffer to the dextrose solution, sterilize it by filtration through a bacteria-retaining porcelain filter, pad, or membrane, or by autoclaving for 30 minutes at 106 kPa (15 lb) (121°C).

The prepared concentrate at a concentration of 5 mg/mL (50 mg amphotericin B in 10 mL sterile water for injection) may be stored in a refrigerator (at 2°C to 8°C) for up to 24 hours protected from light. The diluted solution (≤0.1 mg/mL amphotericin B) should be used immediately after preparation, but it is not necessary to protect it from light during administration.

Warning. Strict aseptic techniques (!) must be observed both during buffer preparation and during infusion, as neither the antibiotic nor the solvent contains preservatives or bacteriostatic agents. All punctures into the powder vial or solvent container must be performed using a sterile needle.

Do not use physiological saline solution (0.9%) for solution preparation. Using a solvent other than the recommended one or the presence of bacteriostatic agents (e.g., benzyl alcohol) in the solvent may cause precipitation of the antibiotic. Do not use the concentrate or the infusion solution if a precipitate or foreign particles are observed in either.

A linear filter may be used for intravenous infusion of amphotericin B; however, the average pore diameter of the filter should not be less than 1.0 micron to ensure passage of the colloidal dispersion.