Abelcet 5 mg/ml lipid complex concentrate for dispersion for infusion

Package leaflet: Information for the user

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Abelcet lipid complex 5 mg/ml, concentrate for dispersion for infusion

Amphotericin B lipid complex

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Abelcet lipid complex is and what it is used for
2. What you need to know before using Abelcet lipid complex
3. How to use Abelcet lipid complex
4. Possible adverse effects
5. Storage of Abelcet lipid complex
6. Contents of the pack and other information

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

Abelcet lipid complex belongs to a group of medicines called systemic antifungals.

Abelcet lipid complex contains amphotericin B in lipid complex, a medicine used to treat serious systemic infections caused by fungi (fungal infections) or by a parasite called Leishmania (visceral leishmaniasis).

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

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

Treatment with Abelcet lipid complex requires hospitalization and must be administered under the supervision of a physician experienced in managing this type of infection.

Do not use Abelcet lipid complex

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

Warnings and precautions

Talk to your doctor or pharmacist before starting to use Abelcet lipid complex.

• If you are taking other medicines that may cause kidney damage, see the section Use of Abelcet lipid complex with other medicines. Abelcet may damage the kidneys. Your doctor or nurse will take blood samples to measure your creatinine (a chemical substance in the blood that reflects kidney function) and levels of electrolytes (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 previously had kidney injury or if you are taking other medicines that may affect your kidney function. Blood samples will also be analyzed to monitor for liver changes and your body's ability to produce new blood cells and platelets. If blood tests show changes in kidney function, or other significant changes, your doctor may administer a lower dose of Abelcet or interrupt treatment.

• If blood tests show that your potassium levels are low, your doctor may prescribe a potassium supplement for you to take during treatment with Abelcet.

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

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

Occasionally, it is necessary to take preventive or therapeutic measures for these reactions using standard doses of acetylsalicylic acid, paracetamol, antihistamines, and antiemetics.

• Before starting treatment with Abelcet lipid complex, you may be given a test dose to detect any allergic-type reactions, consisting of a small amount of the medicine followed by 30 minutes of observation before continuing the infusion.

• If you have any liver disease, due to the possibility of abnormalities in liver function tests.

Use of Abelcet lipid complex with other medicines

Inform your doctor or pharmacist if you are using or have recently used any other medicines, including those obtained without a prescription.

Some medicines may interfere with the action of Abelcet lipid complex, either enhancing or reducing its effects, and conversely, Abelcet lipid complex may interfere with the action of other medicines. It is therefore particularly important to inform your doctor if you are taking any other medicines, especially:

• Nephrotoxic medicines (those causing kidney damage)
• Zidovudine (a medicine used to treat infection with the virus that causes AIDS)
• Cyclosporine (a medicine used to prevent transplant rejection)
• Corticosteroids (anti-inflammatory and immunosuppressive medicines)
• Corticotropin (used in diagnosis of adrenal function)
• Antineoplastic agents (medicines used to treat cancer)
• Digitalis glycosides (medicines used for heart conditions, such as digoxin)
• Flucytosine (an antifungal medicine)
• Muscle relaxants (medicines used to treat muscle spasms)

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine.

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

There are no data available to determine whether amphotericin B passes into breast milk. As a precautionary measure, breastfeeding should be discontinued during treatment with Abelcet lipid complex.

Driving and use of machines

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

Abelcet lipid complex contains sodium

This medicine contains 71.8 mg of sodium (main component of table/cooking salt) per 20 ml vial. This corresponds to 3.59% of the maximum daily recommended sodium intake for an adult.

3. How to use Abelcet lipid complex

Consult your doctor or pharmacist if you have any questions.

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

It is always given by intravenous route. Abelcet lipid complex, once prepared and diluted to the appropriate concentration in an infusion bag, will be administered once daily by slow intravenous infusion through a needle or catheter placed in a vein, over approximately 1–2 hours.

Before receiving the first full dose, your doctor will assess whether you are allergic to this medicine by administering a small test dose. You should be aware that the results of this test are not always conclusive.

Your doctor will determine the dose and duration of treatment based on your body weight and the type of infection. Your response will also be monitored and, if necessary, appropriate adjustments will be made.

The recommended dose is as shown in the following table:

Treatment in children is carried out using doses comparable to those recommended in 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 more Abelcet lipid complex than you should

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

If you forget to use Abelcet lipid complex

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

If you stop using Abelcet lipid complex

Your doctor will determine the treatment to be administered at all times and will monitor your response in order to make timely adjustments if necessary. However, if you have any other questions about the use of this product, ask your doctor.

4. Possible adverse effects

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

Listed below are the adverse effects reported with the use of Abelcet lipid complex, detailing the frequency with which they have been observed. The description of frequency corresponds to the following classification:

Very common: affects more than 1 in 10 patients
Common: affects between 1 and 10 in 100 patients
Uncommon: affects between 1 and 10 in 1,000 patients
Rare: affects between 1 and 10 in 10,000 patients
Very rare: affects fewer than 1 in 10,000 patients
Frequency not known: cannot be estimated from available data.

Very common

• Increased blood creatinine (a waste product that accumulates when kidney function is impaired).
• Chills, fever.

Common

• Increased alkaline phosphatase in blood, increased blood urea (signs of impaired liver and kidney function).
• Increased heart rate, heart rhythm disturbances including severe palpitations, decreased heart rate, irregular heartbeat with intermittent pulse, syncope, serious heart rhythm disturbances.
• Decrease in red blood cells, white blood cells, and platelets.
• Headache, tremors, drowsiness, mental confusion.
• Asthma, difficulty breathing, shortness of breath, respiratory disturbances, chest pain, reduced oxygen supply during breathing.
• Diarrhea, nausea, vomiting, gastrointestinal bleeding including rectal and gingival bleeding, abdominal pain.
• Worsening kidney function including kidney failure, presence of blood in urine, reduced urine output.
• Rash (redness of the skin due to allergic reaction).
• Increased blood acidity (acidosis), disturbances in body fluid distribution. Increased blood levels of bilirubin, increased potassium levels, decreased magnesium levels, loss of appetite.
• Infection, sepsis (systemic infection).
• Increased or decreased blood pressure.
• Generalized weakness, fluid accumulation in organs and tissues, reaction at the injection site, chest pain.
• Abnormal liver function tests.

Uncommon

• Elevation of liver blood values (ALT, AST, CPK, LDH), decreased creatinine renal clearance, abnormalities in electrocardiogram, reduced pulmonary function tests, increased body weight.
• Heart failure, bluish discoloration of skin and mucous membranes, palpitations.
• Blood coagulation disorders, anemia due to destruction of red blood cells, tendency to bleed, decrease in all blood cells (coagulopathy, eosinophilia, hemolytic anemia, leukemoid reaction, pancytopenia).
• Agitation, involuntary limb movements, tingling, cramps, seizures, disorientation, stupor, slurred speech, dizziness, neck stiffness, difficulty thinking, difficulty walking.
• Hearing loss, tinnitus.
• Cough, fluid accumulation in the lungs, respiratory failure, rhinitis.
• Abnormal stools, constipation, dry mouth, altered taste, indigestion, burning and acid reflux, difficulty swallowing, flatulence, pancreatitis, mouth ulcers, changes in tongue coloration.
• Complete absence of urine, kidney damage, urinary abnormalities.
• Red skin spots, excessive sweating, small red spots on the skin, itching, skin allergy with swelling, skin discoloration, skin sores, urticaria.
• Joint pain, bone pain, muscle spasms, muscle pain.
• Decreased blood acidity (alkalosis), increased blood lipids, increased sodium levels, accumulation of uric acid.
• Blood vessel disorders, pallor, inflammation of veins (phlebitis), pulmonary artery blockage, fainting, blood vessel dilation, liver disease due to venous congestion.
• Back pain, allergic reaction at injection site, malaise, multi-organ failure.
• Generalized reaction, allergic phenomena, rejection reactions to transplanted tissues.
• Gallstones, hepatitis, liver damage, combined liver and kidney damage, yellowing of the skin and eyes (jaundice).
• Anxiety, nervousness.

Frequency not known

• Bronchial spasms (bronchospasm).
• Increased urine volume and sensation of thirst (nephrogenic diabetes insipidus).

The adverse effects associated with conventional amphotericin B may also occur with Abelcet lipid complex. Your doctor should monitor for these possibilities.

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effects not listed in this leaflet, inform your doctor or pharmacist.

The adverse 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, although the adverse effect profile is similar to that in younger adults, increased blood creatinine and breathing difficulties occur more frequently.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Abelcet lipid complex

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the container following EXP. The expiry date is abbreviated (EXP) such that the first two digits indicate the month and the four digits following the slash indicate the year. The expiry date refers to the last day of that month.

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

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

After dilution for use, the suspension remains stable for 24 hours at 2–8°C. Each vial is for single use only. Discard any unused portion in the vial. Do not store for later use.

Chemical and physical in-use stability has been demonstrated for 48 hours under refrigeration (+2°C to +8°C) and for 6 hours at room temperature (+15°C to +25°C).

From a microbiological standpoint, Abelcet lipid complex should be used immediately, as it contains no preservatives to prevent possible contamination. If not used immediately, the times and conditions of in-use storage prior to administration are the responsibility of the user and should generally not exceed 24 hours at 2°C to 8°C, unless reconstitution and dilution have been carried out under controlled and validated aseptic conditions.

Medicines must not be disposed of via wastewater or household waste. Dispose of containers and unused medicines at the SIGRE collection point at the pharmacy. If in doubt, consult your pharmacist on how to dispose of unused medicines and their containers. This will help protect the environment.

6. Contents of the pack and other information

Composition of Abelcet lipid complex

• The active substance is: amphotericin B
• The other components are:

L-α-dimyristoylphosphatidylcholine (DMPC)
L-α-dimyristoylphosphatidylglycerol (DMPG) (in the form of sodium and ammonium salts)
Sodium chloride
Water for injections

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

Appearance of the product and contents of the pack

Abelcet lipid complex is a yellow, sterile, pyrogen-free suspension supplied in single-dose glass vials of type I, containing 10 ml or 20 ml. The vials are sealed with a silicone stopper and an aluminum cap.

It is supplied in boxes of 10 vials of 10 ml and in boxes of 10 vials of 20 ml. Not all presentations may be commercially available.

Marketing Authorization Holder

Teva Pharma, S.L.U.
C/ Anabel Segura 11, Edificio Albatros B, 1st Floor,
Alcobendas 28108 Madrid, Spain

Manufacturer

Merckle GmbH
Graf-Arco-Str. 3
89079 Ulm, Germany

For further information about this medicinal product, please contact the Marketing Authorization Holder:

Teva Pharma, S.L.U.
C/ Anabel Segura 11, Edificio Albatros B, 1st Floor,
Alcobendas 28108 Madrid, Spain

Date of the most recent review of this summary: June 2022

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Preparation of Abelcet lipid complex

Abelcet is a sterile, pyrogen-free concentrate that must be diluted and administered only by intravenous infusion.

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

Disposal of unused medicinal product and of all materials that have been in contact with it must be carried out in accordance with local regulations.

A STRICT ASEPTIC TECHNIQUE MUST BE FOLLOWED DURING HANDLING OF ABELCET LIPID COMPLEX, AS IT DOES NOT CONTAIN BACTERIOSTATICS OR PRESERVATIVES.

When initiating treatment with Abelcet lipid 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 provided in this section. Once prepared, approximately 1 mg of the infusion should be administered to the patient over a period of 15 minutes. After administering this amount, the infusion should be interrupted and the patient should be carefully observed for 30 minutes. If the patient shows no signs of hypersensitivity, the infusion may continue. The results of this test are not always definitive.

The following instructions must be observed when preparing the infusion suspension

1. Remove the vial from the refrigerator and allow it to reach room temperature for a few minutes; gently shake until no yellow sediment is visible at the bottom.
2. Withdraw the appropriate dose of Abelcet lipid complex from the required number of vials using one or more sterile 20 ml syringes equipped with a 17 to 19G needle.
3. Remove the needles from each syringe filled with Abelcet lipid complex and replace them with the 5-micron filter needle supplied with each vial.
4. Insert the filter needle into a 5% glucose bag and empty the syringe contents into the bag. Each filter needle should be used only to filter the contents of one vial, and a new filter must be used for each subsequent vial.

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

The intravenous infusion should be administered at a rate of 2.5 mg/kg/hour. It is especially recommended to use an infusion pump.

If Abelcet lipid complex is administered through an existing intravenous line, the line must first be flushed with 5% glucose, or a dedicated line should be used for the infusion.

Do not use the preparation after dilution with 5% glucose if there is evidence of contamination.

The vials are for single use only. Discard any unused portion in the vial. Do not store for later use.

ABELCET LIPID COMPLEX MUST ONLY BE DILUTED IN 5% DEXTROSE SOLUTION AND MUST NOT BE DILUTED IN SALINE SOLUTIONS OR MIXED WITH OTHER MEDICINAL PRODUCTS OR ELECTROLYTES.

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