AMBISOME 50 mg Powder

Contents of the leaflet

1. PATIENT INFORMATION LEAFLET
2. Leaflet accompanying the packaging: patient information
3. AmBisome liposomal
4. 50 mg powder for dispersion for infusion
   1. Read the contents of the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
5. What is AmBisome liposomal and what is it used for
   1. What is AmBisome liposomal
   2. AmBisome liposomal is administered by intravenous infusion (drip) in a hospital by
   3. Indications for use of AmBisome liposomal
6. Important information before using AmBisome liposomal
   1. When not to use AmBisome liposomal
   2. The doctor will not administer AmBisome liposomal
   3. Warnings and precautions
   4. The doctor will exercise special caution when using AmBisome liposomal. The patient should inform the doctor:
   5. AmBisome liposomal and other medicines
   6. Medicines that may cause kidney damage
   7. Medicines that may decrease potassium levels
   8. If you are taking any of these medicines, tell your doctor.
   9. Other medicines
   10. If you are taking any of these medicines, tell your doctor.
   11. Pregnancy and breastfeeding
   12. If you are pregnant, breastfeeding, think you may be pregnant, or plan to have a child, tell your doctor before starting AmBisome liposomal
   13. Driving and using machines
   14. AmBisome liposomal contains sucrose and sodium
   15. Sucrose
   16. Sodium
7. How to use AmBisome liposomal
   1. AmBisome liposomal should NOT be used interchangeably with other products containing amphotericin B.
   2. Use in adults
   3. Systemic and/or deep-seated fungal infections - one or more internal organs
   4. Mucormycosis
   5. Cryptococcal meningitis
   6. Visceral leishmaniasis
   7. Suspected fungal infections in patients with fever and neutropenia
   8. Use in children and adolescents
   9. Use in elderly patients
   10. Use in patients with renal impairment
   11. Infusion time
   12. Using a higher dose of AmBisome liposomal than recommended
8. Possible side effects
   1. Side effects that may occur during infusion. If the patient experiences a severe infusion-related reaction, the doctor will discontinue AmBisome liposomal administration and recommend avoiding this medicine in the future.
   2. Very common side effects (may affect more than 1 in 10 people)
   3. Common side effects (may affect up to 1 in 10 people)
   4. Uncommon side effects (may affect up to 1 in 100 people)
   5. Frequency not known (frequency cannot be estimated from available data)
   6. Reporting side effects
9. How to store AmBisome liposomal
10. Contents of the packaging and other information
    1. What AmBisome liposomal contains
    2. What AmBisome liposomal looks like and what the packaging contains
    3. Marketing authorization holder
    4. Manufacturer
    5. Date of last revision of the leaflet:
    6. INFORMATION INTENDED FOR HEALTHCARE PROFESSIONALS ONLY
    7. BEFORE PREPARING THE SOLUTION, READ THE FOLLOWING TEXT CAREFULLY.
    8. DO NOT use AmBisome liposomal interchangeably with other products containing amphotericin B.
    9. Only properly trained personnel should prepare the AmBisome liposomal solution.
    10. The AmBisome liposomal solution should be prepared using sterile water for injection (without a bacteriostatic agent) and diluted only with a glucose solution for infusion.
    11. Example preparation of AmBisome liposomal infusion solution at a dose of 3 mg/kg body weight/day in 5% glucose solution for infusion
    12. Shelf life after reconstitution
    13. Shelf life after dilution with a glucose solution
    14. Stability of AmBisome liposomal after reconstitution with water for injection and further dilution with a glucose solution (in PVC or polyolefin bags)

PATIENT INFORMATION LEAFLET

Leaflet accompanying the packaging: patient information

AmBisome liposomal

50 mg powder for dispersion for infusion

Amphotericin B
Amphotericin B in liposomes

Read the contents of the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or nurse. See section 4.

Table of contents of the leaflet

• 1. What is AmBisome liposomal and what is it used for
• 2. Important information before using AmBisome liposomal
• 3. How to use AmBisome liposomal
• 4. Possible side effects
• 5. How to store AmBisome liposomal
• 6. Contents of the packaging and other information

1. What is AmBisome liposomal and what is it used for

What is AmBisome liposomal

AmBisome liposomal is an antifungal antibiotic. The active substance of AmBisome liposomal is amphotericin B in liposomes.

AmBisome liposomal is administered by intravenous infusion (drip) in a hospital by

a doctor or nurse.

Indications for use of AmBisome liposomal

• Systemic and/or deep-seated fungal infections - one or more internal organs.
• Suspected fungal infectionin patients with fever and neutropenia. Neutropenia is a condition where there is a low number of white blood cells called neutrophils in the blood. They are important in fighting infections. Neutropenia can be a side effect of cancer treatment. Before administering AmBisome liposomal, the doctor will check if the fever is not caused by bacteria or viruses. The patient has probably already received at least one antibiotic. Persistent fever despite treatment may be caused by a fungal infection.

Fungal infections that can be effectively treated with AmBisome liposomal include: disseminated candidiasis, aspergillosis, mucormycosis, cryptococcal meningitis, visceral leishmaniasis.
The medicine should not be used to treat common fungal infections without clinical symptoms, diagnosed only on the basis of positive skin test results or serological tests.

2. Important information before using AmBisome liposomal

When not to use AmBisome liposomal

The doctor will not administer AmBisome liposomal

• If the patient is allergic (hypersensitive)to amphotericin B or any of the other ingredients of AmBisome liposomal, unless the doctor believes that the patient's life is at risk and AmBisome liposomal is the only possible medicine to use. The medicine should not be used if the patient has previously experienced a severe anaphylactic or anaphylactoid reactionto AmBisome liposomal - a sudden, life-threatening allergic reaction that usually manifests as sudden redness of the skin, itching, nausea and vomiting, facial swelling, tongue, mouth and throat, and swelling that often makes breathing difficult.

Warnings and precautions

The doctor will exercise special caution when using AmBisome liposomal. The patient should inform the doctor:

• If the patient experiences a severe allergic reaction (anaphylactic), the doctor will discontinue the administration of the medicine (see section 4. "Possible side effects").
• If the patient experiences other reactions that may be related to intravenous infusion, the doctor may decide to reduce the rate and extend the duration of the AmBisome liposomal infusion (up to about 2 hours). To treat infusion-related reactions or prevent their occurrence, the doctor may also administer medications to the patient, such as an antihistamine, a pain reliever, and/or an anti-inflammatory or immunosuppressive medication (see section 4. "Possible side effects").
• If the patient is taking other medicines that may cause kidney damage. See: "AmBisome liposomal and other medicines". AmBisome liposomal may cause kidney damage. The doctor or nurse will take blood samples to test the level of creatinine (a substance whose level in the blood indicates kidney function) and electrolytes (especially potassium and magnesium) before and during treatment with AmBisome liposomal - the level of these compounds may be abnormal in people with kidney function disorders. This is especially important if the patient has previously experienced kidney damage or is taking other medicines that may cause kidney damage. Blood samples will also be analyzed for changes in liver function and the body's ability to produce cells and platelets.
• If the blood test results show kidney function disorders or other significant changes, the doctor may reduce the dose of AmBisome liposomal or discontinue treatment.
• If the blood test results indicate low potassium levels in the patient's blood, the doctor may prescribe a potassium supplement to be taken during AmBisome liposomal treatment.
• If the blood test results indicate high potassium levels in the patient's blood. The patient may experience irregular heartbeat, sometimes severe.
• If the patient has recently received a white blood cell transfusion. If AmBisome liposomal is administered during or shortly after white blood cell transfusion, severe pulmonary complications may occur. To reduce the risk of these complications, the doctor will recommend infusions with the longest possible time interval and will monitor the patient's lung function.
• If the patient is undergoing hemodialysis or ultrafiltration due to kidney failure, the doctor will recommend administering AmBisome liposomal after these procedures.

AmBisome liposomal and other medicines

Tell your doctorabout all medicines you are currently taking, or have recently taken, and any medicines you plan to take.

Medicines that may cause kidney damage

• Medicines that weaken the body's natural defenses(immunosuppressive), such as cyclosporine.
• Certain antibiotics, called aminoglycosides, including gentamicin, neomycin, and streptomycin.
• Pentamidine, a medicine used to treat pneumonia in patients with AIDS and leishmaniasis.

If you are taking any of these medicines, tell your doctor. AmBisome liposomal may increase the kidney damage caused by these medicines. If you are taking these medicines, your doctor or nurse will regularly take blood samples to test kidney function.

Medicines that may decrease potassium levels

• Corticosteroids, anti-inflammatory medicines that weaken the immune system.
• Corticotropin(ACTH), a hormone that regulates the production of corticosteroids by the body in response to stress.
• Diuretics, which increase the amount of urine excreted, including furosemide.
• Digitalis glycosides(medicines derived from digitalis), used to treat heart failure. AmBisome liposomal may increase the side effects of digitalis glycosides, such as changes in heart rhythm.
• Muscle relaxants, usually used during surgery, such as tubocurarine. AmBisome liposomal may increase the muscle relaxant effect.

If you are taking any of these medicines, tell your doctor.

Other medicines

• Antifungal medicines, such as flucytosine. AmBisome liposomal may increase the side effects of flucytosine - disorders of new blood cell production by the body, which can be detected in blood tests. Certain anticancer medicines, such as methotrexate, doxorubicin, carmustine, and cyclophosphamide. Co-administration with AmBisome liposomal may cause kidney damage, wheezing, breathing difficulties, and low blood pressure. White blood cell transfusions (leukocytes)may cause severe pulmonary complications during or shortly after white blood cell transfusion if the patient has been administered AmBisome liposomal. The doctor will recommend administering these medicines with the longest possible time interval and will monitor lung function. This will reduce the risk of pulmonary complications.

If you are taking any of these medicines, tell your doctor.

Pregnancy and breastfeeding

If you are pregnant, breastfeeding, think you may be pregnant, or plan to have a child, tell your doctor before starting AmBisome liposomal

AmBisome liposomal.
The doctor will prescribe AmBisome liposomal to a pregnant patient only if they believe that the benefits of treatment outweigh the potential risks to the patient and their unborn child.
It is not known whether the medicine passes into breast milk. When deciding whether to breastfeed during AmBisome liposomal treatment, the doctor will consider: the potential risks to the child, the benefits of breastfeeding for the child, and the benefits of AmBisome liposomal treatment for the mother.

Driving and using machines

No studies have been conducted on the effects on driving and using machines.
Some side effects of AmBisome liposomal may affect the ability to drive and use machines (see section 4. "Possible side effects"). Do not drive or use machines if you experience: seizures, heart rhythm disorders, or other side effects that may impair your physical and mental abilities.

AmBisome liposomal contains sucrose and sodium

Sucrose

Each vial of AmBisome liposomal contains about 900 mg of sucrose (sugar). If you have diabetes or have previously been diagnosed with intolerance to certain sugars, tell your doctor before starting AmBisome liposomal.

Sodium

The medicine contains less than 1 mmol (23 mg) of sodium per vial, which means it is considered "sodium-free".

3. How to use AmBisome liposomal

AmBisome liposomal is intended for use only under the supervision of a doctor or medical professional. It is administered intravenously (by drip). AmBisome liposomal should not be administered by any other route.
To prepare the infusion, AmBisome liposomal should be dissolved in sterile water for injection, and then diluted with a glucose solution. Do not mix AmBisome liposomal with saline solutions or other medicines or electrolytes.
The dosage of AmBisome liposomal is determined by the doctor individually for each patient, based on their weight and indications.

AmBisome liposomal should NOT be used interchangeably with other products containing amphotericin B.

Use in adults

Systemic and/or deep-seated fungal infections - one or more internal organs

Treatment usually starts with a daily dose of 3 mg/kg body weight for at least 14 days. The doctor may decide to increase the daily dose of AmBisome liposomal to 5 mg/kg body weight.

Mucormycosis

In cases of suspected or confirmed mucormycosis, the initial dose is usually 5 to 10 mg/kg body weight per day. Patients with brain involvement or post-transplant patients should receive a dose of 10 mg/kg body weight per day. The duration of treatment will be determined individually by the doctor

Cryptococcal meningitis

Induction treatment (14 days) with a high dose in HIV-infected patients:
on day 1, a singledose of 10 mg/kg body weight of AmBisome liposomal, in combination with 100 mg/kg body weight/day of flucytosine and 1200 mg/day of fluconazole;
for the next 14 days - continuation of treatment with flucytosine 100 mg/kg body weight and fluconazole 1200 mg administered once a day.
Maintenance treatment
after a 2-week induction period, patients should receive fluconazole at a dose of 800 mg/day for 8 weeks, and then
after 8 weeks - fluconazole at a dose of 200 mg/day, at the doctor's discretion

Visceral leishmaniasis

Patients with normal immune function: administer a dose of 3 mg/kg body weight on days 1-5, 14, and 21.
Patients with impaired immunity: administer a dose of 4 mg/kg body weight on days 1-5,

• 10, 17, 24, 31, and 38.

Suspected fungal infections in patients with fever and neutropenia

Treatment starts with a dose of 3 mg/kg body weight, once a day, for 10 to 14 days or until neutropenia resolves.

Use in children and adolescents

AmBisome liposomal has been administered to children aged 1 month to 18 years.
The dose of AmBisome liposomal for children is calculated in the same way as for adults, based on body weight. The efficacy and safety of AmBisome liposomal in children under 1 month of age are unknown.

Use in elderly patients

No dose adjustment is necessary.

Use in patients with renal impairment

Patients with renal impairment have been administered AmBisome liposomal at daily doses of 1 to 5 mg/kg body weight. No dose adjustment is necessary. During AmBisome liposomal treatment, the doctor or nurse will regularly take blood samples to test kidney function.

Infusion time

Intravenous infusion usually lasts 30 to 60 minutes, and the patient will be closely monitored during the procedure. If the dose exceeds 5 mg/kg body weight per day, a 2-hour intravenous infusion is recommended. The recommended concentration of amphotericin B for intravenous infusion is between 0.2 mg/ml and 2 mg/ml.

Using a higher dose of AmBisome liposomal than recommended

Inform your doctor immediately if you think you have received too much AmBisome liposomal.
If you have any further questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, AmBisome liposomal can cause side effects, although not everybody gets them.

Side effects that may occur during infusion. If the patient experiences a severe infusion-related reaction, the doctor will discontinue AmBisome liposomal administration and recommend avoiding this medicine in the future.

Very common (may affect more than 1 in 10 people):fever, chills.
Less common infusion-related reactions include:feeling of pressure, chest pain, shortness of breath, bronchospasm causing breathing difficulties (may be accompanied by wheezing), redness of the skin, rapid heartbeat, low blood pressure, and muscle or joint pain (described as joint pain, back pain, or bone pain).
These symptoms usually resolved quickly after the infusion was discontinued. These reactions may not occur during subsequent administrations of AmBisome liposomal or when the infusion rate is slower (administered over more than 2 hours). The doctor may prescribe other medicines to prevent possible infusion-related reactions or treat their symptoms.

Very common side effects (may affect more than 1 in 10 people)

Feeling of fatigue, confusion, muscle weakness or muscle cramps due to low potassium levels in the blood.
Nausea or vomiting.
Fever, chills.

Common side effects (may affect up to 1 in 10 people)

Feeling of fatigue, confusion, muscle weakness or muscle cramps due to low magnesium, calcium, or sodium levels in the blood.
High blood sugar levels.
Headache.
Rapid heartbeat (tachycardia).
Vasodilation, low blood pressure, redness of the skin.
Shortness of breath.
Diarrhea.
Abdominal pain.
Rash.
Chest pain.
Back pain.
Abnormal liver or kidney function test results detected in blood or urine samples.
High potassium levels in the blood.

Uncommon side effects (may affect up to 1 in 100 people)

Petechiae, ecchymoses, and prolonged bleeding after injury.
Severe allergic reaction (anaphylactoid).
Seizures.
Breathing difficulties, which may be accompanied by wheezing.

Frequency not known (frequency cannot be estimated from available data)

Anemia (reduced red blood cell count in the blood, which can cause excessive fatigue, shortness of breath after minor physical exertion, and pale skin).
Severe allergic reactions (anaphylactic) and hypersensitivity reactions.
Sudden cardiac arrest and arrhythmias.
Kidney failure or dysfunction. Symptoms include fatigue and decreased urine output.
Severe swelling of the lips, eyes, or tongue.
Muscle pain due to breakdown of striated muscle fibers (rhabdomyolysis).
Muscle or joint pain (described as joint pain, back pain, or bone pain).
Disorders of phosphate levels in the blood. A false-positive result indicating elevated phosphate levels in the blood of patients treated with AmBisome liposomal may occur if the samples are analyzed using a specific method with the PHOSm reagent.
If the test result indicates high phosphate levels in the blood, it may be necessary to repeat the test using a different method to verify the result.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. Side effects can be reported directly to the Department of Drug Safety Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301,
Fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medicine

5. How to store AmBisome liposomal

Keep the medicine out of the sight and reach of children.
Do not use AmBisome liposomal after the expiry date stated on the packaging.
Store in a temperature below 25°C. Store in the original packaging.
Do not store partially used vials for further use.
More information on the storage of the medicinal product can be found at the end of the leaflet, in the section "Information intended for healthcare professionals only".

6. Contents of the packaging and other information

What AmBisome liposomal contains

The active substance is amphotericin B. Each vial contains 50 mg of amphotericin B in liposomes.
The other ingredients are: soybean phosphatidylcholine, hydrogenated (HSPC), distearoylphosphatidylglycerol, sodium salt (DSPG), cholesterol, sucrose, alpha-tocopherol, disodium edetate, sodium hydroxide, hydrochloric acid.

What AmBisome liposomal looks like and what the packaging contains

AmBisome liposomal is a sterile, light yellow lyophilisate (freeze-dried powder) for dispersion for infusion. The medicine is supplied in 15 ml, 20 ml, or 30 ml glass vials. Each vial contains 50 mg of the active substance, amphotericin B.
The closure consists of a rubber stopper, an aluminum cap, and a plastic flip-off cap.
Each carton contains 1 vial and 1 membrane filter or 10 vials and 10 membrane filters.
Not all pack sizes may be marketed.

Marketing authorization holder

Gilead Sciences Ireland UC
Carrigtohill
County Cork
T45 DP77
Ireland

Manufacturer

Gilead Sciences Ireland UC
IDA Business & Technology Park
Carrigtohill
County Cork
Irlandia
To obtain more detailed information about this medicine, please contact the representative of the marketing authorization holder:
Gilead Sciences Poland Sp. z o.o.
ul. Postępu 17A
02-676 Warszawa
tel.: 22 262 87 02

Date of last revision of the leaflet:

INFORMATION INTENDED FOR HEALTHCARE PROFESSIONALS ONLY

BEFORE PREPARING THE SOLUTION, READ THE FOLLOWING TEXT CAREFULLY.

DO NOT use AmBisome liposomal interchangeably with other products containing amphotericin B.

Only properly trained personnel should prepare the AmBisome liposomal solution.

The AmBisome liposomal solution should be prepared using sterile water for injection (without a bacteriostatic agent) and diluted only with a glucose solution for infusion.

Using other solutions or the presence of a bacteriostatic agent (e.g., benzyl alcohol) may cause the AmBisome liposomal particles to precipitate out of solution.
Due to INCOMPATIBILITY, do not reconstitute AmBisome liposomal with saline solutions or dilute it with saline solutions, or administer it through the same intravenous line as a saline solution, unless the intravenous line has been flushed with a glucose solution for infusion first. If this is not possible, AmBisome liposomal should be administered through a separate intravenous line.
DO NOT mix AmBisome liposomal with other medicines or electrolytes.
When preparing the solution, strictly follow aseptic procedures, as neither AmBisome liposomal nor the solutions used to reconstitute and dilute the concentrate contain preservatives or bacteriostatic agents.
Preparing the solution containing 50 mg of amphotericin B

• 1. Add 12 ml of sterile water for injection to one vial of AmBisome liposomal to obtain a suspension with an amphotericin B concentration of 4 mg/ml.
• 2. IMMEDIATELYafter adding water, SHAKE THE VIAL VIGOROUSLYfor 30 seconds to obtain a uniformly dispersed AmBisome liposomal suspension. Check for visible particulate matter and continue shaking until a uniform suspension is obtained. Do not administer if particulate matter is observed.
• 3. Calculate the volume of the reconstituted AmBisome liposomal suspension (4 mg/ml) to be further diluted (see the table below).
• 4. The infusion solution is prepared by diluting the reconstituted AmBisome liposomal suspension with a glucose solution for infusion (5%, 10%, or 20%) in a volume of 1 to 19 parts, resulting in a final concentration of 2.00 mg/ml to 0.20 mg/ml of amphotericin B in liposomes (see the table below).
• 5. Draw up the calculated volume of the reconstituted AmBisome liposomal suspension into a sterile syringe using the filter provided with the packaging. Inject it into a sterile container containing the calculated volume of glucose solution for infusion.

AmBisome liposomal infusion solution can be administered using a membrane filter, provided with the packaging. The average pore size of the filter should not be less than 1 micron.

Example preparation of AmBisome liposomal infusion solution at a dose of 3 mg/kg body weight/day in 5% glucose solution for infusion

To one vial of AmBisome liposomal (50 mg), add 12 ml of sterile water for injection to obtain an amphotericin B concentration of 4 mg/ml.
Partially used vials should not be stored for further use.
Any unused product or waste materials should be disposed of in accordance with local regulations.

Shelf life after reconstitution

Since the product does not contain preservatives - from a microbiological point of view, AmBisome liposomal should be used immediately after reconstitution in water or dilution with a glucose solution.
The person administering the medicine is responsible for the conditions and shelf life of the medicine after opening and before administration to the patient.
The shelf life after reconstitution of the medicinal product in sterile water for injection is 24 hours at a temperature of 2°C-8°C, provided that the medicinal product was reconstituted under controlled and validated aseptic conditions.
The solution may be stored under conditions in which its chemical and physical stability has been demonstrated, i.e.:
in glass vials: 24 hours at a temperature of 25±2°C or up to 7 days at a temperature of 2°C-8°C;
in polypropylene syringes: up to 7 days at a temperature of 2°C-8°C.
Do not store partially used vials for further use.

Shelf life after dilution with a glucose solution

Storage in PVC or POE (polyolefin) infusion bags - according to the data in the table below.

Stability of AmBisome liposomal after reconstitution with water for injection and further dilution with a glucose solution (in PVC or polyolefin bags)

Store in PVC or POE (polyolefin) infusion bags at a temperature of 25±2°C or 2°C-8°C. Do not freeze.