DACARBAZINE MEDAC 1000 mg POWDER FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Dacarbazine medac 500mg powder for solution for infusion

Dacarbazine medac 1,000mg powder for solution for infusion

Dacarbazine

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of the pack

1. What Dacarbazine medac is and what it is used for
2. What you need to know before you are given Dacarbazine medac
3. How Dacarbazine medac is used
4. Possible side effects
5. Storage of Dacarbazine medac
6. Contents of the pack and other information

1. What Dacarbazine medac is and what it is used for

Dacarbazine belongs to a group of medicines known as cytostatic agents. These agents affect the growth of cancer cells.

Your doctor has prescribed Dacarbazine medac for the treatment of cancer, such as:

• advanced malignant melanoma (skin cancer);
• Hodgkin's disease (cancer of the lymphatic tissue);
• soft tissue sarcoma (cancer of muscles, fat tissue, fibrous tissue, blood vessels or other supporting tissue of the body).

Dacarbazine medac may be used in combination with other cytostatic agents.

2. What you need to know before you are given Dacarbazine medac

You will not be given Dacarbazine medac

• if you are allergic to dacarbazine or any of the other ingredients of this medicine (listed in section 6);
• if your white blood cell and/or platelet count is too low (leucopenia and/or thrombocytopenia);
• if you have severe liver or kidney disease;
• if you are pregnant or breastfeeding.

Warnings and precautions

Talk to your doctor or pharmacist before you are given Dacarbazine medac.

Before each administration, you will have blood tests to check that you have enough blood cells to receive this medicine. Your kidney and liver function will also be checked.

You should not be given a live vaccine if you are receiving Dacarbazine medac. This is because Dacarbazine medac can weaken your immune system and make you more likely to have a severe infection.

You must not use fotemustine if you are receiving Dacarbazine medac.

Other medicines and Dacarbazine medac

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

You should not use any other medical treatment without telling your doctor, as interactions may occur between Dacarbazine medac and other medicines.

In particular, tell your doctor or pharmacist if you are using or being treated with any of the following:

• Radiation therapy or other medicines to reduce tumor growth (chemotherapy). The use of these medicines with Dacarbazine medac may increase damage to the bone marrow.
• Other medicines that are metabolized by a liver enzyme system called cytochrome P450.
• Methoxsalen (used for skin problems such as psoriasis and eczema): the use of Dacarbazine medac with methoxsalen may make you more sensitive to sunlight (photosensitization).
• Phenytoin (used to treat seizure disorders): the use of Dacarbazine medac with phenytoin may make you more likely to have seizures (convulsions).
• Cyclosporin or tacrolimus (used to reduce immune system reactions): these medicines may weaken your immune system.
• Fotemustine (used to treat skin cancer): the use of Dacarbazine medac with fotemustine may damage your lungs.
• During chemotherapy, you should avoid medicines that can cause liver damage, such as diazepam (used to treat anxiety, muscle spasms, and seizures), imipramine (used to treat depression symptoms), ketoconazole (used to treat fungal infections), and carbamazepine (used to prevent seizures, modify some types of pain, or control mood disorders).
• Anticoagulants (medicines used to prevent blood clot formation): your doctor will decide whether to give you these medicines and will perform blood coagulation tests.

You should not be given a live vaccine if you are receiving Dacarbazine medac or for 3 months after the end of treatment with Dacarbazine medac. This is because Dacarbazine medac can weaken your immune system and make you more likely to have a severe infection.

You can be given a killed or inactivated vaccine while receiving Dacarbazine medac.

Use of Dacarbazine medac with alcohol

Do not drink alcohol during chemotherapy.

Pregnancy, breastfeeding, and fertility

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

The medicine may harm the fetus.

Do not use dacarbazine if you are pregnant, think you may be pregnant, or plan to become pregnant.

Do not breastfeed while receiving treatment with Dacarbazine medac.

Women of childbearing age/Contraception in men and women

If you are a woman and wish to become pregnant, you should consult your doctor so that you can be referred to a specialist before the scheduled start of treatment and after treatment.

If you are a man, you are advised to seek advice on sperm preservation before the scheduled start of treatment.

Women of childbearing age must use effective contraceptive measures while being treated with dacarbazine and for 6 months after the end of treatment.

Men must use effective contraceptive measures and not father a child while being treated with dacarbazine and for 3 months after the end of treatment.

Driving and using machines

Your ability to drive or operate machines may be affected due to side effects on the central nervous system (effects on the brain and nerves) or due to dizziness and vomiting; however, there is no reason you cannot drive or use machines between courses of treatment with this medicine, unless you feel dizzy or unsteady.

3. How Dacarbazine medac is used

This medicine will be administered under the direction of a specialist doctor in oncology (cancer treatment) or hematology (study of blood diseases). You will have regular check-ups during and after treatment to detect any signs of side effects.

Dacarbazine is a light-sensitive substance. The doctor or nurse administering this medicine will ensure that dacarbazine is protected from sunlight during administration.

How much Dacarbazine medac you will be given

Your doctor will calculate the dose that you will be given. It will depend on the type of cancer you have and how advanced it is, your body surface area (m²), your blood counts, and any other medicines or treatments you are using to treat cancer. The doctor treating you will also decide individually how long you will receive this medicine.

Your doctor may change the dose and frequency of administrationbased on the results of your blood tests, your general condition, other treatments, and your response to this medicine. If you have any questions about your treatment, ask your doctor, nurse, or pharmacist.

Skin cancer (malignant melanoma)

The usual dose is 200-250 mg per m² of body surface area, once a day. You will be given this dose for 5 consecutive days, every 3 weeks. It will be administered by rapid injection into a vein or by slow infusion into a vein over 15-30 minutes.

Alternatively, you may receive a higher dose of 850 mg per m² of body surface area, every 3 weeks. This dose will be administered by slow infusion into a vein.

Lymphatic tissue cancer (Hodgkin's disease)

The usual dose is 375 mg per m² of body surface area, every 15 days. You will also be given other medicines called doxorubicin, bleomycin, and vinblastine (this combination is called the ABVD regimen). It will be administered by slow infusion into a vein.

Cancer of muscle, fat, or fibrous tissue, blood vessels, or other connective tissue of the body (soft tissue sarcoma)

The usual dose is 250 mg per m² of body surface area, once a day. You will be given this dose for 5 consecutive days, every 3 weeks. It will be administered by slow infusion into a vein over 15-30 minutes.

You will also be given a medicine called doxorubicin (this combination is called the ADIC regimen).

Patient with kidney or liver problems

If you have mild or moderate kidney or liver problems, you will not usually need to receive a lower dose of this medicine. If you have both kidney and liver problems, your body will take longer to use and eliminate the medicine. Your doctor may give you a lower dose of this medicine.

Use in children

Until more data are available, it is not possible to provide special recommendations to your doctor for the pediatric use of this medicine.

If you have been given too much Dacarbazine medac

If you have been given too much Dacarbazine medac, you may experience a severe decrease in blood cells. This can lead to complete loss of bone marrow function. Possible symptoms include signs of infection, bruising due to increased bleeding tendency, or fatigue. These symptoms may occur up to 2 weeks later.

If you think you have been given too much Dacarbazine medac, tell your doctor or nurse immediately. They will check your blood cell count and may need to take supportive measures such as transfusions.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Your doctor will discuss these side effects with you and explain the risks and benefits of your treatment.

Tell your doctor immediately if you notice any of the following:

• Signs of infection, such as sore throat and fever
• Unusual bruising or bleeding
• Extreme tiredness
• Persistent or severe vomiting or diarrhea
• Severe allergic reaction: you may experience a sudden rash that itches, swelling of hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing) and you may feel like you are going to faint
• Yellowing of the skin and eyes due to liver problems
• Signs of brain or nerve problems, such as headaches, vision problems, seizures, confusion, lethargy, or numbness and tingling in the face
• Severe liver problems due to blockage of the liver blood vessels (veno-occlusive disease [VOD] or Budd-Chiari syndrome), with destruction of liver cells (liver necrosis), which can be fatal. If these complications are suspected, your doctor will decide on the correct treatment for you.

These are serious side effects. You may need urgent medical attention.

The following side effects may occur:

Common(may affect up to 1 in 10 people)

• Decrease in the number of red blood cells (anemia), white blood cells (leucopenia), and/or platelets (thrombocytopenia) in the blood

These changes in blood counts depend on the dose and are delayed; the lowest values usually occur only after 3 to 4 weeks.

• Lack of appetite (anorexia), dizziness, and vomiting (all of which can be severe)

Uncommon(may affect up to 1 in 100 people)

• Hair loss (alopecia)
• Darkening of the skin (hyperpigmentation)
• Sensitivity to light (photosensitivity) in the skin
• Flu-like symptoms, with fatigue, chills, fever, and muscle pain. These symptoms may occur during administration of the medicine or a few days after receiving it. They may also recur the next time you are given dacarbazine
• Infections

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

• Decrease in the number of all blood cells (pancytopenia)
• Severe decrease in the number of granulocytes, a special type of white blood cells (agranulocytosis)
• Severe allergic reaction (anaphylactic) that causes, for example, low blood pressure, swelling of hands, feet, ankles, face, lips, mouth, and throat (which may cause difficulty swallowing or breathing), and you may feel like you are going to faint
• Headaches
• Vision problems
• Confusion
• Lethargy
• Seizures (convulsions)
• Abnormal sensations in the face (facial paresthesia), numbness, and redness of the face shortly after injection
• Diarrhea
• Increased liver enzymes
• Kidney function problems
• Reddening of the skin (erythema)
• Rash (maculopapular exanthema)
• Hives (urticaria)
• Irritation at the injection site

If this medicine is accidentally injected into the tissue near the vein, it can be painful and may cause tissue damage.

You may experience one or more of these symptoms. If you experience any side effects, talk to your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Dacarbazine medac

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

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date is the last day of the month shown.

Do not store above 25°C. Store the vial in the outer packaging to protect it from light.

The shelf life in these conditions is 3 years.

Reconstituted solution of Dacarbazine medac

Freshly prepared (reconstituted) solutions of Dacarbazine medac have been shown to be stable for 48 hours at 2-8°C protected from light. From a microbiological point of view, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user and normally should not exceed 24 hours at 2-8°C, unless the reconstitution has been carried out in validated and controlled aseptic conditions.

Reconstituted and further diluted solution of Dacarbazine medac

Reconstituted and further diluted solutions of Dacarbazine medac have been shown to be stable for 24 hours at 2-8°C protected from light in polyethylene containers and glass vials, and for 2 hours at 25°C in polyethylene containers. From a microbiological point of view, freshly prepared (reconstituted) and further diluted solutions of Dacarbazine medac should be used immediately.

Dacarbazine medac is for single use only.

After use, your doctor should discard any remaining medicine, as well as solutions in which the appearance of the medicine has changed. Your doctor should visually inspect the diluted solution for infusion and only use solutions that are clear and practically free of particles.

6. Container Content and Additional Information

Composition of Dacarbazina medac

• The active ingredient is dacarbazine (as dacarbazine citrate).
• The other components are anhydrous citric acid and mannitol.

Appearance of the Product and Container Content

Dacarbazina medac is a white or pale yellow powder supplied in amber-colored glass vials (Type I, Ph.Eur.).

Each single-use vial of Dacarbazina medac 500 mg contains 500 mg of dacarbazine, as dacarbazine citrate.

After reconstitution and final dilution, Dacarbazina medac 500 mg contains 1.4 – 2.0 mg/ml of dacarbazine.

Each single-use vial of Dacarbazina medac 1,000 mg contains 1,000 mg of dacarbazine, as dacarbazine citrate.

After reconstitution and final dilution, Dacarbazina medac 1,000 mg contains 2.8 – 4.0 mg/ml of dacarbazine.

The vials of Dacarbazina medac are packaged in boxes of 1 vial.

Only certain pack sizes may be marketed.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

Marketing Authorization Holder and Manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Phone: +49 (0)4103 8006-0

Fax: +49 (0)4103 8006-100

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Laboratorios Gebro Pharma S.A,

Phone: +34 93 205 86 86

This medicine is authorized in the Member States of the European Economic Areaand in the United Kingdom (Northern Ireland)under the following names:

Germany Detimedac 500 mg/1,000 mg, powder for solution for infusion

Austria Dacarbazine medac 500 mg/1,000 mg, powder for solution for infusion

Belgium DACARBAZINE MEDAC 500 mg/1,000 mg, powder for solution for infusion

DACARBAZINE MEDAC 500 mg/1,000 mg, powder for solution for perfusion

DACARBAZINE MEDAC 500 mg/1,000 mg, powder for solution for infusion

Denmark Dacarbazine medac 500 mg, powder for infusion solution

Spain Dacarbazina medac 500 mg/1,000 mg, powder for solution for perfusion

Ireland Dacarbazine medac 500 mg/1,000 mg, powder for solution for infusion

Italy Dacarbazina medac 500 mg/1,000 mg, powder for solution for infusion

Netherlands Dacarbazine medac 500 mg/1,000 mg, powder for solution for infusion

Portugal Dacarbazina medac 500 mg/1,000 mg, powder for solution for perfusion

United Kingdom Dacarbazine medac 500 mg/1,000 mg, powder for solution for infusion

Sweden Dacarbazine medac 500 mg/1,000 mg, powder for infusion solution

Date of the last revision of this leaflet: 12/2023.

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended exclusively for healthcare professionals:

Recommendations for safe handling

Dacarbazine is a cytostatic agent and should be handled in accordance with the standard procedures for cytostatics with mutagenic, carcinogenic, and teratogenic effects. Before starting, local guidelines on cytotoxics should be consulted.

Dacarbazine should only be opened by trained personnel, and as with all cytotoxic agents, precautions should be taken to avoid exposing personnel. Generally, during pregnancy, handling of cytotoxic medicines should be avoided. Preparation of the solution for administration should be carried out in a designated area for handling, working over a washable tray or a disposable absorbent paper with a plastic backing.

Adequate protection for the eyes, disposable gloves, mask, and disposable apron should be used. Syringes and infusion equipment should be assembled with care to avoid leaks (use of a Luer-type connection is recommended).

After completion, all exposed surfaces should be thoroughly cleaned, and hands and face should be washed.

In case of spillage, operators should wear gloves, masks, eye protection, and disposable aprons, and should collect the spilled material with an absorbent material placed in the area for this purpose. The area should then be cleaned, and all contaminated material should be transferred to a bag or container for cytotoxic spills, or sealed for incineration.

Preparation for intravenous administration

Dacarbazine solutions should be prepared at the time of use.

Dacarbazine is photosensitive. During administration, the container holding the infusion solution and the administration equipment should be protected from exposure to sunlight, using, for example, light-resistant PVC infusion equipment. Standard infusion equipment should be wrapped, for example, in a UV-resistant material.

• Preparation of Dacarbazina medac 500 mg:

Transfer 50 ml of water for injection aseptically to the vial and shake until a solution is obtained. The resulting solution, which contains 10 mg/ml of dacarbazine (solution density: p = 1.007 g/ml), should be further diluted with 200-300 ml of a 0.9% sodium chloride or 5% glucose infusion solution. The obtained infusion solution, which contains 1.4-2.0 mg/ml of dacarbazine, is ready for IV infusion and should be administered over a period of 20-30 minutes.

• Preparation of Dacarbazina medac 1,000 mg:

Transfer 50 ml of water for injection aseptically to the vial and shake until a solution is obtained. The resulting solution, which contains 20 mg/ml of dacarbazine (solution density: p = 1.015 g/ml), should be further diluted with 200-300 ml of a 0.9% sodium chloride or 5% glucose infusion solution. The obtained infusion solution, which contains 2.8-4.0 mg/ml of dacarbazine, is ready for IV infusion and should be administered over a period of 20-30 minutes.

Dacarbazina medac 500 mg (1,000 mg) is for single use.

The diluted infusion solution should be visually inspected, and only clear solutions practically free of particles should be used. Solutions with particles present should not be used.

Any solution with a changed appearance should be discarded.

Disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations.