Prospect:Information for the User

AmBisome liposomal50 mg powder for solution for infusion

Amphotericin B (in liposomes)

Read this prospect carefully before this medicine is administered to you because it contains important information for you.

-Keep this prospect, as you may need to read it again.

-If you have any questions, consult your doctor.

-If you experience any adverse effects, consult your doctor even if they are not listed in this prospect. See section 4.

Contents of the package and additional information

Ambotericin B is an antifungal, used for the treatment of severe infections caused by fungi. This medication is indicated for:

-Treatment of severe systemic infections caused by fungi.

-Treatment of infections suspected to be caused by fungi in patients with severe neutropenia (patients with a reduced number of a type of white blood cells called "neutrophils"), as a result of blood diseases or due to the use of cytotoxic or immunosuppressive drugs.

-Treatment of visceral Leishmaniasis, a disease caused by a parasite.

No use AmBisome liposomal

• If you are allergic (hypersensitive) to amphotericin B or to any of the other components of this medicine listed in section 6.

Warnings and precautions

Consult your doctor before starting to use this medicine.

• -If you have previously experienced a severe anaphylactoid or anaphylactic reaction to this medicine (an immediate allergic reaction, potentially fatal, with symptoms of flushing, itching, dizziness, swelling of the face, mouth, tongue, and respiratory tract, often severe enough to cause breathing difficulties).

If this occurs, your doctor will stop the treatment.

-If you experience other reactions that are thought to be related to the infusion.. If this occurs, your doctor may reduce the infusion rate so that you receive this medicine over a longer period of time (approximately 2 hours). Your doctor may also give you medicines, such as diphenhydramine (an antihistamine), paracetamol, pethidine (an analgesic), and/or hydrocortisone (an anti-inflammatory drug that acts by reducing the response of your immune system), to prevent or treat reactions related to the infusion rate.

-If you are taking other medicines that may cause kidney damage,see the section Other medicines and AmBisome. AmBisome may damage the kidneys. Your doctor or nurse will take blood samples to measure your creatinine (a chemical in the blood that reflects kidney function) and electrolyte levels (especially potassium and magnesium) before and during treatment with AmBisome, as both may be abnormal if you have changes in kidney function. This is especially important if you have had previous kidney damage or if you are taking other medicines that may affect kidney function. Blood samples will also be analyzed to detect changes in the liver and your body's ability to produce new blood cells and platelets.If blood tests show a change in kidney function, or other important changes, your doctor may give you a lower dose of AmBisome or stop treatment.

-If blood tests show that your potassium levels are low.If this occurs, your doctor may prescribe a potassium supplement for you to take while you are receiving AmBisome.

-If blood tests show that your potassium levels are high., you may experience irregular heartbeats, sometimes severe.

-If your blood test results show a change in kidney function or other important changes. If this occurs, your doctor may give you a lower dose of the medicine or stop treatment.

• If you are receiving or have recently received a transfusion of leucocytes (white blood cells). As there may be sudden and severe problems in the lungs, your doctor will advise you to separate the infusions as much as possible to reduce the risk of lung problems, and will monitor the function of the lungs.
• If you are receiving haemodialysis or filtration for kidney failure. Your doctor may start the treatment with this medicine once the procedure has finished.
• Interference with the results of phosphate values in blood tests when using a specific system, called the PHOSm assay, may result in false readings that show an increase in phosphate levels in the blood.

If your blood test results show elevated phosphate levels, additional tests may be necessary using a different system to confirm the results.

• If you are diabetic. This medicine contains approximately 900 milligrams of saccharose (sugar) in each vial.

Other medicines and AmBisome liposomal. Use of other medicines

Inform your doctor if you are using or have recently used or may need to use any other medicine.

The following medicines interact with amphotericin B and may interact with this medicine.

• Medicines that may be harmful to the kidneys,including:

• Nephrotoxic drugs (drugs that damage the kidneys) such as ciclosporin.
• Aminoglycoside antibiotics (drugs used to treat bacterial infections) such as gentamicin, neomycin, and streptomycin.
• Pentamidine, a drug used to treat pneumonia in patients with AIDS and leishmaniasis.

These medicines may damage the kidneys and AmBisome liposomal may worsen the damage caused by these medicines to the kidneys. If you are taking medicines that may damage the kidneys, your doctor or nurse will take blood samples periodically to analyze changes in kidney function.

• Medicines that may reduce your potassium levels,including:

• Corticosteroids (anti-inflammatory drugs that act by reducing the response of your immune system) and corticotropin (ACTH), used to control the rate of production of natural corticosteroids in the body in response to stress.
• Diuretics (drugs that increase urine production), such as furosemide.
• Digitalis glycosides, drugs produced from the digitalis plant, used to treat heart failure. This medicine may decrease the level of potassium in the blood, worsening the effects of digitalis (heart rhythm alterations).
• Muscle relaxants (e.g., tubocurarine). This medicine may increase the muscle-relaxing effect.

• Other medicines

• Antifungal drugs (drugs used to treat fungal infections), such as flucytosine. This medicine may worsen the side effects of flucytosine (changes in the body's ability to produce new blood cells, reflected in blood tests).
• Cancer chemotherapy drugs (anticancer drugs), such as methotrexate, doxorubicin, carmustine, and cyclophosphamide. The use of this type of medicine during infusion of this medicine may cause kidney damage, respiratory distress, or low blood pressure.
• Leucocyte transfusions (white blood cell transfusions). Severe and sudden problems in the lungs have been described in patients treated with amphotericin B. See also,Be especially careful with AmBisome liposomal

Pregnancy and lactation

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medicine.

The safety of this medicine in pregnant women is unknown. If you are pregnant, your doctor will only prescribe this medicine if they believe that the benefits of treatment outweigh the potential risks for you and your baby.

The safety of this medicine in breastfeeding women is unknown. While receiving this medicine, the potential risk to the baby should be weighed against the benefits of breastfeeding for the baby and the benefits of AmBisome liposomal treatment for the mother.

Driving and operating machinery

Some of the side effects of this medicine may affect your ability to drive vehicles or use machines safely (see section 4 on possible side effects).

AmBisome liposomal contains sodium

This medicine contains less than 23 mg (1 mmol) of sodium per dose, making it essentially "sodium-free".

Your doctor or nurse will administer this medication personally to you.

If you are a patient undergoing dialysis, your doctor should start administering this medication when each dialysis session has ended (see the sectionTake special care with AmBisome liposomalliposomal)

Your doctor will indicate the dose of this medication that you should receive, based on your specific needs. It is administered by intravenous infusion over a period of 30 to 60 minutes, once a day.

The recommended dose of AmBisomeliposomalis:

• 1-3 mg/kg of body weight per day, for the treatment ofconfirmed or suspected fungal infections. This dose may be increased to 5 mg/kg of body weight per day if the infection is severe.
• For mucormycosis, the initial dose is generally 5 mg/Kg of body weight per day. Your doctor will assess the dose and determine the duration of treatment individually. Treatment should be continued until the signs and symptoms of the infection have disappeared.
• 1 to 1.5 mg/kg of body weight per day, for 21 days or 3 mg/kg of body weight per day for 10 daysfor the treatment of visceral leishmaniasis.
  

If you havevisceral leishmaniasis, you will receive this medication for 10 or 21 days. If you are re-infected, you may need additional treatment, either longer or shorter, to control the infection (also known as maintenance therapy).

If you use more AmBisomeliposomalthan you should

Inform your doctor or nurse immediately if you think you have received too much AmBisomeliposomal.

Inform your doctor or nurse immediately if you experience any of the adverse effects listed in section 4 of this leaflet, as some of them may occur if you receive too much AmBisomeliposomal. If you have received too much AmBisomeliposomal, your doctor will perform a detailed monitoring and, if necessary, will provide treatment for the symptoms of overdose.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, Teléfono (91) 5 62 04 20, indicating the medication and the amount ingested.

If you forgot to use AmBisomeliposomal

Your doctor will decide whether you need to receive an additional dose of this medication if a dose has been missed.

If you interrupt treatment with AmBisomeliposomal

Your doctor will indicate the duration of your treatment with this medication based on your specific needs. Do not interrupt treatment with this medication, even if you are feeling better, before your doctor makes that decision, as your disease may continue if you do not receive the complete treatment.

Like all medicines, AmBisomeliposomalcan cause side effects, although not everyone will experience them.

The most common infusion-related reactions that can be expected are fever, chills, and rigors. Other less common infusion-related reactions may include chest tightness, chest pain, shortness of breath, difficulty breathing (possibly with wheezing), redness, rapid heart rate, low blood pressure, and musculoskeletal pain (described as joint pain, back pain, or bone pain). All of these reactions will disappear immediately upon stopping the infusion. These reactions do not necessarily occur with subsequent AmBisomeliposomalinfusions or if the infusion rate is reduced (for 2 hours). Your doctor may administer other medications to slow down infusion-related reactions or to treat symptoms if they occur. If you experience a severe infusion-related reaction, your doctor will stop the AmBisomeliposomalinfusion and you should not receive this treatment in the future.

The following side effects have occurred during treatment with AmBisomeliposomal:

Very common: may affect more than 1 in 10 people:

• Feeling of fatigue, confusion, weakness, or muscle cramps caused by low potassium levels in the blood.
• Feeling of dizziness or nausea.
• Fever, chills, or rigors, stiffness.

Common: may affect up to 1 in 10 people:

• Feeling of fatigue, confusion, weakness, or muscle cramps caused by low magnesium, calcium, or sodium levels in the blood.
• Increased blood sugar levels.
• Headache.
• Rapid heart rate.
• Dilation of blood vessels, low blood pressure, and redness (flushing of the skin).
• Shortness of breath.
• Diarrhea, abdominal pain.
• Abnormal liver or kidney function test results observed in blood or urine tests.
• Skin rash.
• Chest or back pain.
• High potassium levels in the blood.

Uncommon: may affect up to 1 in 100 people:

• Bleeding in the skin, unexplained bruises, or prolonged bleeding after an injury.
• Anaphylactoid reaction (for information on anaphylactoid reactions, see section 2 of this leaflet).
• Seizures (attacks or crises).
• Difficulty breathing, possibly with wheezing (popping sounds).

In addition, the following side effects have been observed during treatment with AmBisome liposomal but it is not known how often they occur.

• Anemia (decrease in the number of red blood cells in the blood, with symptoms of excessive fatigue, shortness of breath after light activity, and paleness).
• Anaphylactic and hypersensitivity reactions (for information on anaphylactic reactions, see section 2 of this leaflet).
• Heart attack and alterations in the normal heart rhythm.
• Renal insufficiency and decreased renal function.
• Intense swelling of the skin around the lips, eyes, or tongue.
• Muscle rupture.
• Bone pain and joint pain.

If you consider that any of the side effects you experience are severe or if any side effect not mentioned in this leaflet appears, inform your doctor.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also

report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es

By reporting side effects, you can contribute to providing more information

on the safety of this medicine.

Keep this medication out of the sight and reach of children

Do not use this medication after the expiration date that appears on the packaging after CAD. The expiration date refers to the last day of the month

Do not store above25ºC.

Any AmBisome liposomal solution that has been reconstituted or diluted and not used immediately should be discarded.

Shelf life of AmBisome liposomal before opening the vialliposomalbefore opening the vial

3 years.

Shelf life of AmBisome liposomal after opening the vial

The following physical and chemical stability data have been demonstrated in use:

• Physical and chemical stability in use afterreconstitution with water for injection:

Glass vials for 24 hours at 25±2ºC exposed to ambient light

Glass vials and polypropylene syringes for up to 7 days at 2-8ºC. Do not freeze.

• Physical and chemical stability in use afterdilutionwith glucose:

Infusion bags: See Table for recommendations

From a microbiological point of view, since AmBisome liposomal does not contain any bacteriostatic agent, the reconstituted or diluted product should be used immediately.

If not used immediately, the times and conditions of storage in use, prior to administration, are the responsibility of the user and should normally not be more than 24 hours at 2-8ºC, unless reconstitution has taken place in controlled and validated aseptic conditions. Do not freeze.

Composition of AmBisome liposomal

• The active ingredient is amphotericin B (in liposomes). Each vial contains 50 mg of amphotericin B (in liposomes)
• The other components are: liposome components (hydrogenated soy phosphatidylcholine, cholesterol, distearoyl phosphatidylglycerol, alpha-tocopherol), the other components: sucrose, disodium succinate hexahydrate, sodium hydroxide, and hydrochloric acid.

Aspect of the product and contents of the package

AmBisome liposomal is a sterile, lyophilized powder, yellow in color, for infusion solution. It is presented in single-dose glass vials. Each vial contains 50 mg of the active ingredient amphotericin B. The closure consists of rubber stoppers sealed with an aluminum ring, provided with a disposable plastic stopper. Each carton contains 10 vials and 10 filters of 5 micras.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Gilead Sciences S.L.

Via de los Poblados, 3 ef 7/8 plta 6ª - Pque

Empresarial Cristalia,

(Madrid) - 28033 - España

Responsible for manufacturing

GILEAD SCIENCES CORK LIMITED

IDA Business and Technology Park (Carrigtohill,

Co. Cork) - - - Irlanda

This leaflet was approved in April 2024

The detailed and updated information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for healthcare professionals: INSTRUCTIONS FOR USE/MANIPULATION

READ THIS SECTION CAREFULLY BEFORE INITIATING RECONSTITUTION

AmBisome liposomal should not be administered if the presence of particles is detected in the infusion solution of the product.

AmBisome liposomal is not physically compatible with saline solutions.

Do not mix AmBisome liposomal with other drugs or electrolytes.

AmBisome liposomal is not interchangeable with other medications containing amphotericin.

AmBisome liposomal should be reconstituted using Sterile Water for Injection (without a bacteriostatic agent) and diluted in a Glucose Solution (5%, 10%, or 20%) for infusion.

The use of any solution other than the recommended ones, or the presence of a bacteriostatic agent (e.g., benzyl alcohol) in the solution, may cause the precipitation of AmBisome liposomal.

AmBisome liposomal is not compatible with saline solutions and cannot be reconstituted or diluted with saline solutions, or administered through an intravenous route that has previously been used for saline solutions, unless it is previously washed with a glucose solution (5%, 10%, or 20%) for infusion. If this is not feasible, AmBisome liposomal should be administered through a different route.

A strict aseptic technique will be followed in all manipulations, since AmBisome liposomal does not contain any bacteriostatic agent or preservative, nor do the materials specified for reconstitution and dilution.

The vials of AmBisome liposomal, containing 50 mg of amphotericin, are prepared as follows:

1.-Add 12 ml of Sterile Water for Injection to each vial of AmBisome liposomal, to obtain a preparation containing 4 mg/ml of amphotericin B.

2.-IMMEDIATELY after adding the sterile water, SHAKE THE VIAL VIGOROUSLY for 30 seconds to disperse the AmBisome liposomal completely. After reconstitution, the concentrate is a yellow translucent dispersion. Do not use if any precipitation of foreign matter is observed..

3.-Calculate the amount of AmBisome liposomal reconstituted (4 mg/ml) for subsequent dilution (see the table below).

The infusion solution is obtained by diluting AmBisome liposomal reconstituted with a volume of between one (1) and nineteen (19) parts of a Glucose Solution (5%, 10%, or 20%) for infusion, to obtain a final concentration in the recommended range of 2 mg/ml to 0.2 mg/ml of amphotericin as AmBisome liposomal (see the table below).

4.-Remove from a sterile syringe the calculated volume of AmBisome liposomal reconstituted. Using the 5-micra filter provided, instill the AmBisome liposomal preparation into a sterile container with the correct amount of Glucose Solution (5%, 10%, or 20%) for infusion.

For the intravenous infusion of AmBisome liposomal, a filter with a membrane in line can be used. However, the average pore diameter of the filter should not be less than 1 micra.

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

* Each vial of AmBisome liposomal (50 mg) is reconstituted with 12 ml of Sterile Water for Injection to provide a concentration of 4 mg/ml of amphotericin B.

Any unused solution of AmBisome liposomal reconstituted or diluted should be discarded (never reused).

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.