Dacarbazine medac 1000 mg powder for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Dacarbazina medac 500mg powder for solution for infusion

Dacarbazina medac 1,000mg powder for solution for infusion

Dacarbazina

Read the entire leaflet carefully before you start using this medicine, because 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 reactions, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Dacarbazina medac is and what it is used for
2. What you need to know before being administered Dacarbazina medac
3. How to use Dacarbazina medac
4. Possible adverse effects
5. How to store Dacarbazina medac
6. Contents of the pack and other information

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

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

Your doctor has prescribed Dacarbazina 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, fatty tissue, fibrous tissue, blood vessels, or other supportive tissues of the body).

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

2. What you need to know before Dacarbazina medac is administered to you

Dacarbazina medac must not be given to you if:

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

Warnings and precautions

Please consult your doctor or pharmacist before Dacarbazina medac is administered to you.

Before each administration, blood tests will be performed to ensure you have enough blood cells to receive this medicine. Your kidney and liver function will also be monitored.

You must not receive a vaccine made with live viruses while you are being treated with Dacarbazina medac. This is because Dacarbazina medac may weaken your immune system and make you more likely to develop a serious infection.

You must not use fotemustine while receiving Dacarbazina medac.

Other medicines and Dacarbazina medac

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

It is not advisable to take any other medical treatment without informing your doctor, as interactions may occur between Dacarbazina medac and other medicines.

Specifically, inform your doctor or pharmacist if you are taking or being treated with any of the following:

• Radiotherapy or other medicines to reduce tumour growth (chemotherapy). Using these medicines together with Dacarbazina medac may increase bone marrow damage.
• Other medicines that are metabolized by a liver enzyme system called cytochrome P450.
• Methoxypsoralen (used for skin conditions such as psoriasis and eczema): using Dacarbazina medac together with methoxypsoralen may make you more sensitive to sunlight (photosensitization).
• Phenytoin (used to treat seizures): using Dacarbazina medac together with phenytoin may make you more likely to experience epileptic seizures (convulsions).
• Cyclosporine or tacrolimus (used to reduce immune system reactions): these medicines may weaken your immune system.
• Fotemustine (used to treat skin cancer): using Dacarbazina medac together with fotemustine may damage your lungs.
• During chemotherapy, medicines that may cause liver damage should be avoided, for example: diazepam (used to treat anxiety, muscle spasms, and seizures), imipramine (used to treat symptoms of depression), ketoconazole (used to treat fungal infections), carbamazepine (used to prevent epileptic seizures, manage certain types of pain, or control mood disorders).
• Anticoagulants (medicines used to prevent blood clots): your doctor will decide whether you should receive these medicines and will perform blood clotting tests.

You must not receive a vaccine made with live microorganisms while you are receiving Dacarbazina medac or within 3 months after treatment with Dacarbazina medac has ended. This is because Dacarbazina medac may weaken your immune system and make you more likely to develop a serious infection.

You may receive a vaccine made with killed or inactivated viruses even while receiving Dacarbazina medac.

Use of Dacarbazina medac with alcohol

You must not consume 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.

This medicine may harm the unborn baby.

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 Dacarbazina medac.

Fertile women / 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 planned start of treatment and after treatment.

If you are a man, it is recommended that you seek advice on sperm preservation before the planned start of treatment.

Women of childbearing age must use effective contraception during treatment with dacarbazine and for 6 months after the end of treatment.

Men must use effective contraception and must not father a child during treatment with dacarbazine and for 3 months after the end of treatment.

Driving and use of machines

Your ability to drive or operate machinery may be affected due to adverse effects on the central nervous system (effects on the brain and nerves), or due to dizziness and vomiting; however, there is no reason preventing you from driving or using machines between treatment cycles with this medicine, unless you feel dizzy or unwell.

3. How to use Dacarbazina medac

This medicine will be administered under the supervision of a specialist physician in oncology (cancer treatment) or hematology (study of blood disorders). You will undergo periodic check-ups during and after treatment to monitor for any signs of adverse effects.

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

How much Dacarbazina medac will be administered to you

Your doctor will calculate the dose to be administered based on the type and stage of your cancer, your body surface area (m²), blood counts, and other medications or treatments you are receiving for cancer. Your treating physician will also determine individually how long you will receive this medicine.

Your doctor may adjust the dose and frequency of administration based 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, please consult your doctor, nurse, or pharmacist.

Skin cancer (metastatic malignant melanoma)

The usual dose is 200–250 mg per m² of body surface area, once daily. This dose will be administered for 5 consecutive days every 3 weeks. It will be given either as a rapid intravenous injection or as a slow intravenous infusion 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 intravenous infusion.

Lymphatic tissue cancer (Hodgkin's disease)

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

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

The usual dose is 250 mg per m² of body surface area, once daily. This dose will be administered for 5 consecutive days every 3 weeks. It will be given by slow intravenous infusion over 15–30 minutes.

You will also receive a medicine called doxorubicin (this combination is known as the ADIC regimen).

Patients with renal or hepatic impairment

If you have mild or moderate kidney or liver problems, you generally will not require a reduced dose of this medicine. If you have both kidney and liver problems, your body may take longer to metabolize and eliminate the medicine. In such cases, your doctor may administer a lower dose.

Use in children

Until additional data become available, no specific recommendations can be provided to your doctor regarding the pediatric use of this medicine.

If you have been given more Dacarbazina medac than you should

If you have been given too much Dacarbazina medac, it may cause a severe drop in blood cells. This could lead to complete loss of bone marrow function. Possible symptoms include signs of infection, bruising due to increased tendency to bleed, or fatigue. These symptoms may appear up to 2 weeks later.

If you think you have been given too much Dacarbazina medac, inform your doctor or nurse immediately. They will check your blood cell counts and supportive measures such as blood transfusions may be necessary.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. Your doctor will discuss these adverse 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
• Bruising or abnormal bleeding
• Extreme tiredness
• Persistent or severe vomiting or diarrhoea
• Severe allergic reaction: you may experience a sudden rash causing itching, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty swallowing or breathing), and 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 impairment, seizures, confusion, drowsiness, or numbness and tingling in the face
• Severe liver problems due to blockage of blood vessels in the liver (veno-occlusive disease [VOD] or Budd-Chiari syndrome), with destruction of liver cells (hepatic necrosis), which may be fatal. If these complications are suspected, your doctor will decide on the appropriate treatment for you.

All of these are serious adverse effects. You may require urgent medical attention.

The following adverse effects may occur:

Common (may affect up to 1 in 10 people)

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

These changes in blood counts are dose-dependent and delayed; the lowest values often occur only after 3 to 4 weeks.

• Loss of appetite (anorexia), dizziness, and vomiting (all of which may be severe)

Uncommon (may affect up to 1 in 100 people)

• Hair loss (alopecia)
• Darkening of the skin (hyperpigmentation)
• Skin sensitivity to light (photosensitivity)
• Flu-like symptoms, including 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 all blood cells (pancytopenia)
• Severe decrease in granulocytes, a specific type of white blood cell (agranulocytosis)
• Severe allergic (anaphylactic) reaction causing, for example, drop in blood pressure, swelling of hands, feet, ankles, face, lips, mouth and throat which may cause difficulty swallowing or breathing, rapid heartbeat, hives, generalized itching or skin redness
• Headaches
• Vision impairment
• Confusion
• Drowsiness
• Seizures (epileptic attacks)
• Abnormal sensations in the face (facial paraesthesia), numbness and redness of the face shortly after injection
• Diarrhoea
• Increased liver enzymes
• Impaired kidney function
• Reddened skin (erythema)
• Skin rashes (maculopapular exanthema)
• Hives (urticaria)
• Irritation at the site of administration

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

You may experience one or more of these symptoms. If you experience any adverse effect, consult your doctor or pharmacist.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Dacarbazina medac

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

Do not use this medicine after the expiry date stated on the label and the carton after EXP. The expiry date refers to the last day of the month indicated.

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

The shelf life under these conditions is 3 years.

Reconstituted Dacarbazina medac solution

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

Reconstituted and further diluted Dacarbazina medac solution

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

Dacarbazina medac is for single use only.

After use, any remaining medicine must be discarded by your physician, as well as any solutions in which the appearance of the medicine has changed. Your physician should inspect the diluted infusion solution visually, and only solutions that are clear and practically free of particles should be used.

6. Contents of the pack and other information

Composition of Dacarbazina medac

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

Appearance of the product and contents of the container

Dacarbazina medac is a white or pale yellow powder supplied in amber 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.

Dacarbazina medac vials are packaged in cartons containing 1 vial.

Only certain pack sizes may be marketed.

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

Marketing Authorisation Holder and Manufacturer

medac Gesellschaft für klinische Spezialpräparate mbH
Theaterstr. 6
22880 Wedel
Germany
Telephone: +49 (0)4103 8006-0
Fax: +49 (0)4103 8006-100

For further information regarding this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Laboratorios Gebro Pharma S.A.,
Tel. +34 93 205 86 86

This medicinal product is authorised in the European Economic Area member states and 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, poudre pour solution pour 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 latest revision of this leaflet: 12/2023

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

This information is intended for healthcare professionals only:

Recommendations for safe handling

Dacarbazine is an antineoplastic agent and must be handled in accordance with standard procedures for cytotoxic drugs that have mutagenic, carcinogenic, and teratogenic effects. Local guidelines on handling cytotoxic agents should be consulted before beginning.

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

Appropriate eye protection, disposable gloves, mask, and disposable gown must be worn. Syringes and infusion sets must be assembled carefully to prevent leakage (use of a Luer-type connection is recommended).

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

In case of spillage, personnel must wear gloves, masks, eye protection, and disposable gowns, and collect the spilled material using absorbent material placed in the designated area. The area must then be cleaned, and all contaminated material must be transferred to a cytotoxic waste bag or container, or sealed for incineration.

Preparation for intravenous administration

Solutions of dacarbazine must be prepared immediately before use.

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

• Preparation of Dacarbazina medac 500 mg:

Aseptically transfer 50 mL of water for injections to the vial and shake until a solution is obtained. The resulting solution, containing 10 mg/mL of dacarbazine (solution density: p = 1.007 g/mL), must be further diluted with 200–300 mL of 0.9% sodium chloride solution for infusion or 5% glucose solution. The resulting infusion solution, containing 1.4–2.0 mg/mL of dacarbazine, is ready for IV infusion and must be administered over 20–30 minutes.

• Preparation of Dacarbazina medac 1,000 mg:

Aseptically transfer 50 mL of water for injections to the vial and shake until a solution is obtained. The resulting solution, containing 20 mg/mL of dacarbazine (solution density: p = 1.015 g/mL), must be further diluted with 200–300 mL of 0.9% sodium chloride solution for infusion or 5% glucose solution. The resulting infusion solution, containing 2.8–4.0 mg/mL of dacarbazine, is ready for IV infusion and must be administered over 20–30 minutes.

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

The diluted infusion solution must be inspected visually; only clear, practically particle-free solutions should be used. Do not use solutions if particles are present.

Any solution that has changed in appearance must be discarded.

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