AMSIDYL 75 mg /1.5 Ml Concentrate

Contents of the leaflet

1. Package Leaflet: Information for the Patient
2. Amsidyl, 75 mg/1.5 ml, Concentrate and Solvent for Solution for Infusion
   1. Read the Package Leaflet Carefully Before Using the Medicinal Product, as it Contains Important Information for the Patient.
   2. Table of Contents of the Package Leaflet
3. What is Amsidyl and what is it used for
4. Important information before using Amsidyl
   1. When not to use Amsidyl:
   2. Warnings and precautions
   3. Children and adolescents
   4. Regular examinations
   5. Amsidyl and other medicines
   6. Pregnancy, breastfeeding, and fertility
   7. Pregnancy
   8. Precautions for men and women to prevent pregnancy
   9. Breastfeeding
   10. Fertility
   11. Driving and using machines
5. How to use Amsidyl
   1. Initial treatment
   2. Continuation of treatment
   3. Use of a higher than recommended dose of Amsidyl
6. Possible side effects
   1. All medicines can cause allergic reactions, and severe allergic reactions are rare. Any sudden onset of wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially affecting the whole body) should be
   2. Reporting side effects
7. How to store Amsidyl
8. Contents of the pack and other information
   1. What Amsidyl contains
   2. What Amsidyl looks like and contents of the pack
   3. Marketing authorization holder and manufacturer
   4. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   5. Member State
   6. Marketing authorization holder
   7. Medicinal product name
   8. Date of last revision of the package leaflet:
   9. Handling and administration of the medicinal product
   10. Shelf life
   11. Disposal

Package Leaflet: Information for the Patient

Amsidyl, 75 mg/1.5 ml, Concentrate and Solvent for Solution for Infusion

Amsacrine

Read the Package Leaflet Carefully Before Using the Medicinal Product, as it Contains Important Information for the Patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet

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

1. What is Amsidyl and what is it used for

Amsidyl belongs to a group of medicines called cytostatics (these are medicines used to treat malignant tumors). It is used to treat acute myeloid leukemia (AML), a type of malignant blood and bone marrow cancer. Amsidyl is used in adults who have not responded to other treatments or in case of disease recurrence.

2. Important information before using Amsidyl

When not to use Amsidyl:

• if you are allergic to amsacrine, acridine derivatives, or any of the other ingredients of Amsidyl (listed in section 6)
• if you are currently receiving (or have recently received) other cancer treatment
• in breastfeeding women.

Before using the medicine, the patient must inform the doctor if any of the above circumstances apply to them.

Warnings and precautions

Before receiving Amsidyl, you should talk to your doctor, pharmacist, or nurse. The doctor will take special precautions if any of the following conditions apply to you.

• You have ever had kidney or liver disease
• You have any heart conditions
• You have low potassium levels in your blood
• You have porphyria. Before using the medicine, the patient must inform the doctor if any of the above circumstances apply to them.

Children and adolescents

Amsidyl is intended for use in adults only. Amsidyl should not be used in children and adolescents under 18 years of age.

Regular examinations

Your doctor will perform regular medical examinations, such as blood tests to check blood morphology, kidney and liver function, as well as heart examinations.

Amsidyl and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take. Many medicines can interact with Amsidyl, which can significantly change their effect. These include:

• Influenza and pneumococcal vaccines
• Live vaccines
• Other medicines used to treat cancer
• Methotrexate used to treat, for example, cancer or rheumatoid arthritis

If you are already taking any of these medicines, you must inform your doctor before taking Amsidyl.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, ask your doctor or pharmacist for advice before using this medicine.

Pregnancy

This medicine can only be used during pregnancy if it is absolutely necessary. The benefits of using the medicine must outweigh the risk to the unborn child.

Precautions for men and women to prevent pregnancy

Women of childbearing age must use effective contraception during treatment and for 3 months after treatment. Men must use effective contraception during treatment and for 6 months after treatment.

Breastfeeding

Do not breastfeed during treatment with Amsidyl.

Fertility

There is evidence that amsacrine has a negative effect on female fertility. Some data suggest a reversible negative effect on male fertility.

Driving and using machines

The effect of Amsidyl on the ability to drive and use machines is unlikely. Nevertheless, if after infusion, you experience side effects such as headache and dizziness, you should be cautious when driving and using machines.

3. How to use Amsidyl

Typically, Amsidyl will be administered in a hospital by a doctor or nurse experienced in the use of cytostatics. Amsidyl will be slowly administered as an infusion into a vein over 1 to 2 hours. The dose will be calculated by the doctor based on the patient's age and body surface area (usually 300-650 mg per square meter during the treatment period).

Initial treatment

The patient will receive one infusion per day for 3-7 days.

Continuation of treatment

After this initial treatment period, subsequent doses will be administered based on the patient's blood cell count. If Amsidyl causes excessive reduction in the patient's blood cell count, a blood transfusion may be necessary. If you have any further questions about the use of this medicinal product, ask your doctor.

Use of a higher than recommended dose of Amsidyl

Since the infusion of the medicine will be performed under the supervision of a doctor, the administration of a higher dose of the medicine than necessary is unlikely. Nevertheless, if you have any doubts about the dose of the medicine, you should discuss this with your doctor. If you have any further questions about the use of the medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

All medicines can cause allergic reactions, and severe allergic reactions are rare. Any sudden onset of wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially affecting the whole body) should be

reported to the doctor immediately.
Very common (may affect more than 1 in 10 people)

• Mild bleeding from the skin and mucous membranes
• Diarrhea, abdominal pain
• Low blood pressure
• Pain and swelling at the injection site due to vein inflammation
• Increased liver function test results
• Mouth inflammation
• Nausea, vomiting.

Common (may affect up to 1 in 10 people)

• Significant reduction in blood cell count, which can cause weakness, bruising, or bleeding, and increase the risk of infection
• Bleeding
• Severe heart problems (e.g., heart failure causing shortness of breath), irregular heartbeat
• Seizures
• Hepatitis, jaundice (which causes yellowing of the skin and whites of the eyes), liver dysfunction
• Blood in the urine
• Peeling skin, skin inflammation
• Infection
• Fever
• Shortness of breath
• Low potassium levels, which can cause muscle weakness, involuntary muscle contractions, or heart rhythm disturbances
• Mood swings
• Hair loss
• Hives, rash
• Irritation at the injection site.

Rare (may affect up to 1 in 1,000 people)

• Other severe heart problems (e.g., life-threatening irregular heartbeat, rapid heartbeat, slow heartbeat, changes in ECG recording)
• Anemia, which is a reduction in red blood cell count, causing pale skin, weakness, or shortness of breath
• Significant reduction in white blood cell count, increasing the risk of infection
• Severe allergic reactions, fluid accumulation in the body, hypersensitivity
• Kidney dysfunction (e.g., lack of urine, kidney failure)
• Weight loss, weight gain
• Lethargy (extreme fatigue or drowsiness), confusion
• Headache, dizziness
• Numbness
• Nerve disorders that can cause weakness, tingling, or numbness
• Vision disturbances
• Protein in the urine
• Abnormal liver and kidney function test results

Unknown (frequency cannot be estimated from available data)

• High levels of uric acid in the blood

The above list of possible side effects may concern you, but remember that acute myeloid leukemia is a serious disease that requires aggressive treatment.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, e-mail: [email protected]. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Amsidyl

Keep the medicine out of the sight and reach of children. Do not store above 25°C. Do not use this medicine after the expiry date stated on the carton after EXP. The expiry date refers to the last day of the month. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Amsidyl contains

• The active substance is amsacrine. Each milliliter of concentrate for solution for infusion contains 50 mg of amsacrine. Each vial contains 75 mg of amsacrine.
• The other ingredients are: dimethylacetamide, (S)-lactic acid, and water for injections.

What Amsidyl looks like and contents of the pack

Amsidyl is supplied in packs consisting of one colorless glass vial containing the concentrate and one colorless glass vial containing the solvent. The vial with the concentrate contains the active substance amsacrine and dimethylacetamide in 1.5 ml of a clear, orange or red solution. The vial with the solvent contains 13.5 ml of a (S)-lactic acid solution in water for injections in the form of a clear solution. Pack size: 1 x 6 vials of concentrate for solution for infusion and 6 vials of solvent for solution for infusion.

Marketing authorization holder and manufacturer

Eurocept International BV, Trapgans 5, 1244 RL Ankeveen, The Netherlands

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Member State

Marketing authorization holder

Medicinal product name

Austria
Amsidyl 75 mg/1.5 ml Konzentrat und Lösungsmittel für das Konzentrat zur Herstellung einer Infusionslösung
Belgium
Amsidine concentraat en oplosmiddel voor oplossing voor infusie
Czech Republic
Amsidyl 75 mg/1.5 ml koncentrát a rozpouštědlo koncentrátu pro infuzní roztok
Denmark
Amekrin 75 mg/1.5 ml koncentrat og solvens til koncentrat til infusionsvæske, opløsning
Finland
Amekrin 75 mg/1.5 ml infuusiokonsentraatti ja liuotin, infuusiokonsentraatti liuosta varten
Germany
Amsidyl Konzentrat zur Herstellung einer Infusionslösung
Iceland
Amekrin 75 mg/1.5 ml Þykkni og leysirfyrir innrennslisþykkni, lausn
Ireland
Amsidine concentrate and solvent for solution for infusion
Italy
Amsadina 75 mg/1.5 ml concentrato e solvente per concentrato per soluzione per infusione
Luxembourg
Amsidine solution à diluer et solvant pour solution pour perfusion
Malta
Amsidine konċentrat u solvent għal soluzzjoni għall-infużjoni
Netherlands
Amsidine concentraat en oplosmiddel voor oplossing voor infusie
Norway
Amekrin 75 mg/1.5 ml konsentrat og væske til konsentrat til infusjonsvæske, oppløsning
Poland
Amsidyl 75 mg/1.5 ml koncentrat i rozpuszczalnik do koncentratu do sporządzania roztworu do infuzji
Portugal
Amekrin 75 mg/1.5 ml concentrado e solvente para concentrado para solução para perfusão
Slovakia
Amsidyl 75 mg/1.5 ml koncentrát a rozpúšťadlo na infúzny koncentrát
Spain
Amekrin 75 mg/1.5 ml concentrado y disolvente para concentrado para solución para perfusión
Sweden
Amekrin 75 mg/1.5 ml koncentrat och vätska till koncentrat till infusionsvätska, lösning
United Kingdom
Amsidine concentrate and solvent for solution for infusion

Date of last revision of the package leaflet:

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Information intended for healthcare professionals only:

Handling and administration of the medicinal product

Handling of cytostatics should be in accordance with national guidelines.
Administration
Intravenous administration. Amsidyl is administered as an intravenous infusion in a glucose solution over 1 to 2 hours. For doses of 125 mg/m or higher, the infusion time should be at least 90 minutes.
Preparation of the medicinal productThe concentrate for solution for infusion must be dissolved with the supplied solvent. The diluted solution is then added to 500 ml of 5% glucose solution. No other solutions should be used than glucose solution. Amsacrine is incompatible with chloride ions. Sodium chloride solutions should not be used. Only glass syringes can be used to draw up and transfer concentrated solutions. 1.5 ml of the concentrate for solution for infusion is transferred aseptically to an injection vial containing the solvent and shaken gently to obtain a clear solution (the concentration of amsacrine in the solution is 5 mg/ml). 75 mg, 90 mg, and 120 mg of amsacrine correspond to 15 ml, 18 ml, and 24 ml of the diluted solution, respectively.
Note: the diluted solution should not be administered until it has been further diluted in at least 500 ml of 5% glucose solution.
Handling
In case of contact with the eyes or mucous membranes, rinse with plenty of water, and in case of contact with the skin, wash immediately with soap and water. If irritation persists after washing, consult a doctor. In case of accidental paravenous administration of the medicine, flush the injection site with a small amount of 5% glucose solution, then cool the affected area immediately. The infusion is discontinued and restarted using a different vein.

Shelf life

Diluted solution (concentrate mixed with solvent, before further dilution):
The diluted solution should be used immediately for further dilution. However, chemical and physical stability has been demonstrated after initial dilution for 48 hours at 2°C – 25°C. After a storage period of 24-48 hours, the diluted solution should be further diluted and used immediately.
Infusion solution:
Chemical and physical stability of the ready-to-use infusion solution has been demonstrated for 48 hours at 2°C – 25°C, provided that there is no evidence that the overall chemical and physical stability period exceeds 48 hours from the initial dilution. From a microbiological point of view, the product should be used immediately. If not used immediately, the storage time and conditions before use are the responsibility of the user, and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

Disposal

Any unused medicinal product or waste materials should be disposed of in accordance with local requirements.