PROSPECTO : INFORMATION FOR THE USER

Abelcet lipid complex5 mg/ml, concentrate for dispersion for infusion

Amphotericin B in lipid complex

Read this prospectus carefully before starting to use this medication, because it contains important information for you.

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

- If you have any doubts, consult your doctor or pharmacist.

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

1. What is Abelcet lipid complex and for what it is used

2. What you need to know before starting to use Abelcet lipid complex

3. How to use Abelcet lipid complex

4. Possible adverse effects

5. Storage of Abelcet lipid complex

6. Contents of the package and additional information

Abelcet complex lipid belongs to the group of medications known as systemic antifungals.

Abelcet complex lipid contains amphotericin B in lipid complex, a medication used in the treatment of severe systemic infections caused by fungi (fungal infections) or by a parasite calledLeishmania(visceral leishmaniasis).

It is also indicated for the prevention of visceral leishmaniasis in patients with AIDS.

The treatment with Abelcet complex lipid requires hospitalization and its administration must be supervised by a specialized doctor in the management of this type of infections.

Do not useAbelcet complex lipid

- If you are allergic (hypersensitive) to amphotericin B or to any of the other components of Abelcet complex lipid.

of Abelcet complex lipid.

Warnings and precautions

Consult your doctor or pharmacist before starting to useAbelcet complex lipid.

• If you are taking other medications that may cause kidney damage, see the sectionUse of Abelcet complex lipid with other medications.Abelcet may damage the kidney. 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 Abelcet, as both may be abnormal if you have changes in kidney function. This is especially important if you have had a previous kidney injury or if you are taking other medications 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 administer a lower dose of Abelcet or interrupt treatment.

• If blood tests show that your potassium levels are low.If this happens, your doctor may prescribe a potassium supplement for you to take while you are being treated with Abelcet.

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

- The first doses of Abelcet complex lipid are often associated with the onset of fever, nausea, and vomiting.

In some cases, measures are taken for prevention or treatment of these

reactions using standard doses of acetylsalicylic acid, paracetamol, antihistamines, and antiemetics.

- Before starting treatment with Abelcet complex lipid, you may be administered a test dose to detect any signs of allergic type, which will consist of a small administration of the drug followed by observation for 30 minutes before proceeding with the infusion.

- If you have any liver disease, due to the possibility of an effect on liver function tests.

Use ofAbelcet complex lipidwith other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, even those purchased without a prescription.

Some medications may interfere with the action of Abelcet complex lipid, either by enhancing or reducing its effects, and Abelcet complex lipid may interfere with the action of other medications, so it is particularly important to communicate with your doctor if you are using any other medication, and especially:

?Nephrotoxic medications (that cause damage to the kidney)

?Zidovudine (medication for the treatment of infection caused by the virus that causes AIDS)

?Cyclosporine (medication for the prevention of rejection in transplants)

?Corticosteroids (anti-inflammatory and immunosuppressive medications)

?Corticotropin (for diagnosis of adrenal function)

?Antineoplastic agents (medications for cancer treatment)

?Digitalis glycosides (medications for heart conditions, such as digoxin)

?Flucytosine (antifungal medication)

?Muscle relaxants (medications for treating muscle spasms)

Pregnancy and lactation

Consult your doctor or pharmacist before using any medication.

Abelcet complex lipid should only be administered to pregnant women in very serious cases, when the beneficial effect of treatment prevails over the possible risks to the mother and fetus.

No data are available to determine if amphotericin B passes into breast milk. As a precaution, it is recommended to stop breastfeeding during treatment with Abelcet complex lipid.

Driving and operating machinery

Do not drive or operate machinery while under treatment, as some of the adverse effects of Abelcet complex lipid may affect your ability to perform such tasks.

Abelcet complex lipidcontains sodium

This medication contains 71.8 mg of sodium (main component of table salt/for cooking) in each 20 ml vial. This is equivalent to 3.59% of the maximum daily sodium intake recommended for an adult.

Consult your doctor or pharmacist if you have any doubts.

Abelcet lipid complex will be administered exclusively by qualified healthcare professionals.

It will always be administered through the intravenous route. Once prepared and diluted to the appropriate concentration in a perfusion bag, Abelcet lipid complex will be administered once a day by slow intravenous infusion, through a needle or catheter placed in a vein, for approximately 1-2 hours.

Before the first full dose is administered, your doctor will assess your allergy to this medication by administering a small test dose. Please note that the results of this test may not always be conclusive.

Your doctor will determine the dose to be administered and the duration of treatment based on your body weight and the type of infection. They will also monitor your response and make any necessary adjustments.

The recommended dose is as shown in the table below:

Treatment in children is administered at doses comparable to those recommended for adults and should also be adjusted according to the patient's body weight.

Treatment in elderly patients does not require dose adjustment.

If you use moreAbelcet lipid complexthan you should

Your doctor will determine the treatment to be administered and monitor your response to make any necessary adjustments if needed. However, if you have any doubts about whether the dose administered to you is higher than it should be, consult your doctor immediately.

If you forget to useAbelcet lipid complex

Your doctor will determine the treatment to be administered and monitor your response to make any necessary adjustments if needed. However, if you have any doubts about whether the dose administered to you is lower than it should be, consult your doctor immediately.

If you interrupt treatment withAbelcet lipid complex

Your doctor will determine the treatment to be administered and monitor your response to make any necessary adjustments if needed. However, if you have any other doubts about the use of this product, ask your doctor..

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

The following side effects have been reported with the use of Abelcet liposomal complex, detailing the frequency at which they have been observed. The description of the frequency of appearance is adjusted to the following correspondence:

Very common: affecting more than 1 in 10 patients

Common: affecting between 1 and 10 in 100 patients

Uncommon: affecting between 1 and 10 in 1,000 patients

Rare: affecting between 1 and 10 in 10,000 patients

Very rare: affecting less than 1 in 10,000 patients

Unknown frequency: cannot be estimated from available data.

Very common

- Elevated creatinine in blood (waste product that accumulates in case of kidney function impairment).

- Chills, fever.

Common

- Elevated alkaline phosphatase in blood, elevated urea in blood (signs of liver and kidney impairment).

- Accelerated heart rate, cardiac rhythm alterations including severe palpitations, decreased heart rate, altered cardiac rhythm with intermittent pulse, syncope, severe cardiac rhythm alterations.

- Decreased red, white blood cells, and platelets in blood.

- Headache, tremors, drowsiness, mental confusion.

- Asthma, difficulty breathing, labored breathing, respiratory alteration, chest pain, decreased oxygen supply during breathing.

- Diarrhea, nausea, vomiting, gastrointestinal bleeding including rectal and gingival bleeding, abdominal pain.

- Renal function deterioration including renal failure, presence of blood in urine, decreased urine output.

- Rash (skin redness due to allergic reaction).

- Increased blood acidity (acidosis), alteration in body fluid distribution. Elevated bilirubin levels, elevated potassium levels, decreased magnesium levels, loss of appetite.

- Infection, sepsis (generalized infection).

- Elevated or decreased blood pressure.

- Generalized weakness, fluid accumulation in organs and tissues, reaction at the injection site, chest pain.

- Abnormal liver function analysis.

Uncommon

- Elevated liver enzymes in blood (ALT, AST, CPK, LDH), decreased renal clearance of creatinine, anomalies in electrocardiogram, decreased pulmonary function tests, increased body weight.

- Heart failure, blue discoloration of skin and mucous membranes, palpitations.

- Blood coagulation alterations, anemia due to red blood cell destruction, bleeding tendency, decreased levels of all blood cells (coagulopathy, eosinophilia, hemolytic anemia, leukemoid reaction, pancitopenia).

- Restlessness, involuntary movements of limbs, paresthesia, cramps, convulsions, disorientation, stupor, confused speech, vertigo, neck stiffness, difficulty thinking, difficulty walking.

- Hearing loss, tinnitus.

- Cough, fluid accumulation in lungs, respiratory failure, rhinitis.

- Abnormal stools, constipation, dry mouth, altered taste, heavy digestion, heartburn, difficulty swallowing, flatulence, pancreatitis, mouth ulcers, changes in tongue color.

- Absence of urine, renal damage, abnormal urine.

- Red spots on skin, excessive sweating, small red spots on skin, itching, skin allergy with swelling, skin discoloration, skin ulcers, urticaria.

- Joint pain, bone pain, muscle spasms, muscle pain.

- Decreased blood acidity (alkalosis), increased blood lipids, increased sodium levels, uric acid accumulation.

- Vascular alterations, pallor, venous inflammation (phlebitis), pulmonary artery obstruction, fainting, vasodilation, hepatic disease due to venous obstruction.

- Back pain, allergic reaction at injection site, discomfort, failure of multiple organs.

- Generalized reaction, allergic phenomena, rejection reaction to transplanted tissues.

- Biliary calculi, hepatitis, hepatic damage, hepatic and renal damage, yellow discoloration of skin and eyes (jaundice).

- Anxiety, nervousness.

Unknown frequency

- Bronchospasm (spasm in bronchi).

- Increased urine volume and sensation of thirst (diabetes insipidus nephrogenic).

The side effects specific to conventional amphotericin B may also occur with Abelcet liposomal complex. Your doctor will need to control this possibility.

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

The side effects observed in children are similar to those observed in adults, with chills and fever being the most common.

In patients over 65 years of age, even though the side effect profile is similar to that of younger adults, elevated creatinine in blood and respiratory difficulty occur more frequently.

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 not appearing in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://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 is abbreviated (CAD) so that the first two numbers indicate the month and the four numbers after the bar indicate the year. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Do not freeze.

Keep the vial in the outer packaging to protect it from light.

Once diluted for use, the suspension remains stable for 24 hours between 2-8°C. Each vial is for single use. Discard the remaining vial not used. Do not store for future use.

Chemical and physical stability has been demonstrated after reconstitution, for 48 hours in refrigerator (+2°C to +8°C) and for 6 hours at room temperature (+15°C to +25°C).

From a microbiological point of view, Abelcet lipid complex should be used immediately since it does not contain preservatives to prevent possible contamination. If not used immediately, the storage times and conditions in use, prior to administration, are the responsibility of the user

and should not generally exceed 24 hours between 2°C and 8°C, unless reconstitution and dilution have been performed in controlled and validated aseptic conditions.

Medicines should not be thrown down the drain or in the trash. Dispose of the packaging and unused

medicines at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and unused medicines. In this way, you will help protect the environment.

Composition ofAmbisome liposomal complex

- The active principle is: amphotericin B

- The other components are:

L-α-dimiristoilfosfatidilcolina (DMPC)

L-α-dimiristoilfosfatidilglicerol (DMPG) (in the form of sodium and ammonium salts)

Sodium chloride

AWater for injection preparations

Ambisome liposomal complex is presented as a concentrate for infusion containing 5 mg of amphotericin B per ml.

Appearance of the product and contents of the package

Ambisome liposomal complex is a yellow suspension, sterile, apyrogenic presented in single-dose glass type I vials, containing 10 ml or 20 ml. The vials are sealed with a silicone stopper and an aluminum crimp.

It is supplied in boxes of 10 vials of 10 ml and in boxes of 10 vials of 20 ml. It is possible that not all presentations are marketed.

Marketing Authorization Holder

Teva Pharma, S.L.U.

C/ Anabel Segura 11, Edificio Albatros B, 1st Floor,

Alcobendas 28108 Madrid

Responsible for manufacturing

Merckle GmbH

Graf-Arco-Str. 3

89079 Ulm

Germany

You can request more information about this medication by contacting the marketing authorization holder:

Teva Pharma, S.L.U.

C/ Anabel Segura 11, Edificio Albatros B, 1st Floor,

Alcobendas 28108 Madrid

Last review date of this leaflet: June 2022

The detailed and updated information about this medication 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:

Preparation ofAmbisome liposomal complex

Ambisome is a sterile and apyrogenic concentrate that must be diluted and administered only by intravenous infusion.

The intravenous infusion must be administered at a rate of 2.5 mg/kg/hour. It is especially recommended to administer it through a perfusion pump. The total duration of treatment will depend on the patient's weight and the disease for which it has been indicated (fungal infection or leishmaniasis), ranging from 1-2 hours.

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

STRICT ASPECTIC TECHNIQUE MUST BE FOLLOWED DURING THE HANDLING OF AMBISOME LIPID COMPLEX, AS IT DOES NOT CONTAIN BACTERIOSTATICS OR PRESERVATIVES.

When starting treatment with Ambisome liposomal complex for the first time, it is recommended to administer a test dose immediately before the first infusion. The infusion suspension must be prepared according to the instructions indicated in this section. Once prepared, it must be administered to the patient approximately 1 mg of the infusion over a period of 15 minutes. Once this amount has been administered, the infusion must be interrupted and the patient must be carefully observed for 30 minutes. If the patient does not show signs of hypersensitivity, the infusion can continue. The results of this test are not always definitive.

To prepare the infusion suspension, the following instructions must be taken into account

1. Remove the vial from the refrigerator and let it reach room temperature, gently agitate until no yellow sediment is observed at the bottom of the vial.
2. Extract the appropriate dose of Ambisome liposomal complex from the vials needed with one or more sterile 20 ml syringes provided with a 17 to 19G needle.
3. Remove the needles from each filled syringe and replace them with the 5-micron filter needle that comes with each vial.
4. Insert the filter needle into a 5% glucose bag and empty the contents of the syringe into the bag. Each filter needle must be used only to filter the contents of one vial, and a new filter must be used for each subsequent vial.

The final concentration of the infusion must be 1 mg/ml. For children or patients with cardiovascular diseases, the medication must be diluted with 5% glucose to achieve a final infusion concentration of 2 mg/ml.

The intravenous infusion must be administered at a rate of 2.5 mg/kg/hour. It is especially recommended to administer it through a perfusion pump.

If the treatment with Ambisome liposomal complex is applied through an intravenous route previously placed, it must be washed with 5% glucose or a new route must be used exclusively for the infusion.

The prepared solution must not be used after dilution with 5% glucose if there is evidence of contamination.

The vials are for single use. Dispose of the unused vial content. Do not store for later use.

AMBISOME LIPID COMPLEX MUST ONLY BE DILUTED IN 5% GLUCOSE SOLUTION AND NOT IN SALINE SOLUTIONS OR MIXED WITH OTHER MEDICINES OR ELECTROLYTES.

After storage in use of the prepared suspension for use, it must be vigorously agitated before use.