Detimedac 100 mg

Package Leaflet: Information for the User

Detimedac 100 mg, powder for solution for injection/infusion

Detimedac 200 mg, powder for solution for injection/infusion

(Dacarbazine)

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

• You should keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

• 1. What is Detimedac and what is it used for
• 2. Before you are given Detimedac
• 3. How Detimedac is given
• 4. Possible side effects
• 5. How to store Detimedac
• 6. Contents of the pack and other information

1. What is Detimedac and what is it used for

Dacarbazine, the active substance in Detimedac, belongs to a group of medicines called cytotoxics. These medicines affect the growth of cancer cells. Detimedac is used to treat cancers such as:

• advanced malignant melanoma (a type of skin cancer)
• Hodgkin's disease (a type of cancer of the lymphatic system)
• soft tissue sarcoma (a type of cancer of muscle, fat, fibrous tissue, blood vessels, or other supporting tissue). Detimedac may be used in combination with other cytotoxic medicines.

2. Before you are given Detimedac

When Detimedac must not be given

• if you are allergic to dacarbazine or any of the other ingredients of this medicine (listed in section 6);
• if you have a low white blood cell or platelet count (leukopeniaand/or thrombocytopenia);
• if you have severe liver or kidney disease;
• if you are pregnant or breastfeeding;
• if you are given a vaccine against yellow fever or at the same time as fotemustine.

Warnings and precautions

Before you start treatment with Detimedac, discuss this with your doctor or pharmacist. Before each dose of Detimedac, a blood test is performed to check if you have a sufficient number of blood cells to receive Detimedac. Your liver and kidney function will also be evaluated.

Detimedac with other medicines

Tell your doctor or pharmacist about all the medicines you are taking, or have recently taken, and about any medicines you plan to take. It is not recommended to take any other medicinal treatment without first informing your doctor, due to the risk of interactions between Detimedac and other medicines. In particular, tell your doctor or pharmacist if you are being treated with:

• Radiation therapy or other medicines used to inhibit the growth of cancer cells (chemotherapy). The use of these medicines with Detimedac may increase the harmful effect on the bone marrow.
• Other medicines that are metabolized by the liver enzyme system called cytochrome P450.
• Methoxsalen - used to treat skin diseases such as psoriasis and eczema. The use of Detimedac with methoxsalen may increase sensitivity to sunlight (phototoxicity).
• Phenytoin - concurrent use of Detimedac and phenytoin increases the risk of seizures (convulsions).
• Cyclosporin or tacrolimus - these medicines can weaken the immune system.
• Fotemustine - Detimedac should not be used until at least one week after fotemustine administration to avoid lung damage.

During chemotherapy, you should avoid taking medicines that can damage the liver (e.g., diazepam, imipramine, ketoconazole, or carbamazepine). Your doctor will decide if you should take medicines that improve blood circulation and check your blood clotting. The recommendations for vaccinations vary depending on the type of vaccine:

• Yellow fever vaccine - you should not be given the yellow fever vaccine if you are being treated with Detimedac.
• Live vaccines - you should not be given live vaccines if you are being treated with Detimedac, as Detimedac may lower your resistance and increase your susceptibility to serious infections.
• Inactivated vaccines - you can be given inactivated or killed vaccines if you are being treated with Detimedac.

Detimedac with food, drink, and alcohol

You should not drink alcohol during chemotherapy.

Pregnancy, breastfeeding, and fertility

Detimedac should not be given if you are pregnant, think you may be pregnant, or plan to have a child. You should not breastfeed during treatment with Detimedac. During treatment with Detimedac, you should use an effective method of contraception. Men should continue to use effective contraception for at least 6 months after the end of treatment with Detimedac.

Driving and using machines

Dacarbazine may affect your ability to drive or use machines due to the possibility of side effects from the central nervous system (affecting the brain and spinal cord) or the possibility of nausea and vomiting; however, there is no reason to stop driving or using machines between treatment cycles, unless you feel dizzy or unsteady.

3. How Detimedac is given

This medicine should always be used under the guidance of a specialist doctor experienced in cancer treatment or hematology (the branch of medicine concerned with blood diseases), with equipment that allows for regular monitoring of all clinical symptoms during and after treatment. Dacarbazine is a light-sensitive substance. The doctor or nurse responsible for administering the medicine will ensure that dacarbazine is administered with protection from daylight.

Administration of Detimedac

Detimedac will be administered by a doctor or nurse in one of the following ways:

• intravenous injection (injection into a vein)
• intravenous infusion (infusion into a vein) - the infusion will last 15 to 30 minutes.

Detimedac 100 mg powder will be dissolved in 10 ml of water for injection immediately before administration, and Detimedac 200 mg powder will be dissolved in 20 ml of water for injection. If the medicine is administered as an intravenous infusion, the solution will be further diluted.

Dose of Detimedac

Your doctor will determine the dose to be administered to you. The dose depends on the type of cancer and the stage of the disease, body surface area (m²), blood cell count results, and other cancer medicines or treatments being used at the same time. Your doctor will determine the duration of treatment with Detimedac for each patient. Your doctor may change the dose and frequency of administrationbased on blood test results, your overall condition, other treatments, and your response to Detimedac. If you have any questions about your treatment, ask your doctor, pharmacist, or nurse. Malignant melanoma with metastases (metastatic malignant melanoma)
The recommended dose is 200 - 250 mg per m² of body surface area, once daily. This dose is administered for 5 consecutive days every 3 weeks. The medicine is administered as a rapid intravenous injection or a slow intravenous infusion lasting 15 - 30 minutes.
Another option is to administer a single large dose of 850 - 1000 mg per m² of body surface area every 3 weeks. This dose will be administered as a slow intravenous infusion.
Hodgkin's disease
The recommended dose is 375 mg per m² of body surface area, every 15 days. You will also receive doxorubicin, bleomycin, and vinblastine (this combination of medicines is called the ABVD regimen). This dose will be administered as a slow intravenous infusion.
Soft tissue sarcoma
The recommended dose is 250 mg per m² of body surface area, once daily. This dose is administered for 5 consecutive days every 3 weeks. The medicine is administered as a slow intravenous infusion lasting 15 - 30 minutes.
You will also receive doxorubicin (this combination of medicines is called the ADIC regimen).

Patients with kidney or liver problems

In patients with mild or moderate kidney or liver problems, it is usually not necessary to reduce the dose of this medicine. In patients with both kidney and liver problems, the metabolism and elimination of the medicine from the body will take longer. Your doctor may recommend a lower dose.

Elderly patients

There are no special recommendations for the use of this medicine in elderly patients.

Use in children

There are no recommendations for the use of dacarbazine in children until further data are available.

Overdose of Detimedac

You should immediately inform your doctor or nurse if you think you have been given more than the prescribed dose of Detimedac.

• In case of suspected overdose, your blood cell count will be checked, and measures may be taken, such as blood transfusion.
• Overdose can cause severe bone marrow damage (toxicity). It can lead to complete loss of bone marrow function (aplastic anemia). It can occur as a delayed reaction, even after two weeks.

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

4. Possible side effects

Like all medicines, Detimedac can cause side effects, although not everybody gets them. Your doctor will inform you about the possibility of side effects and explain the risks and benefits of treatment.

You should immediately inform your doctor if you notice:

• infection symptoms such as sore throat and high fever;
• unusual bruising or bleeding;
• increased fatigue;
• persistent or severe diarrhea or vomiting;
• severe allergic reactions - sudden rash with itching, swelling of hands, feet, ankles, face, lips, mouth, or throat (which may lead to difficulty swallowing or breathing) or feeling like you are about to faint;
• yellowing of the skin and eyes due to liver problems;
• brain or nervous system disorders, such as headaches, vision disturbances, seizures, confusion, lethargy (drowsiness), or numbness and tingling.

All of the above symptoms are serious side effects. You may need urgent medical attention.

Other side effects may also occur:

Common (may affect up to 1 in 10 people)

• Decreased red blood cell count (anemia)
• Decreased white blood cell count (leukopenia)
• Decreased platelet count (thrombocytopenia) Changes in blood cell counts are dose-dependent and occur with a delay, and the minimum values are often observed only after 3 - 4 weeks.
• Lack of appetite (anorexia), nausea, vomiting (all of these symptoms can be severe).

Uncommon (may affect up to 1 in 100 people)

• Hair loss
• Increased skin pigmentation (discoloration)
• Skin sensitivity to light (phototoxicity)
• Flu-like symptoms with fatigue, chills, fever, and muscle pain. These symptoms may occur during or after administration of the medicine. They may also recur during subsequent administration of dacarbazine.
• Infections

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

• Decreased number of all blood cells (pancytopenia)
• Severe decrease in the number of a specific type of white blood cell (agranulocytosis)
• Severe allergic reactions (anaphylaxis) characterized by: low blood pressure, swelling of hands, feet, ankles, face, lips, mouth, or throat, which may lead to difficulty swallowing or breathing, rapid heartbeat, hives, and generalized redness or itching of the skin
• Headaches
• Vision disturbances
• Confusion
• Lethargy (drowsiness)
• Seizures (convulsions)
• Abnormal sensations in the face (facial paresthesia), numbness, and sudden redness of the face immediately after injection.
• Diarrhea
• Severe liver disorder caused by blockage of liver blood vessels (veno-occlusive disease [VOD] or Budd-Chiari syndrome with liver cell death [liver necrosis]), which can be life-threatening. If these complications are suspected, your doctor will determine the appropriate treatment.
• Increased liver enzyme activity
• Redness of the skin (erythema)
• Skin rash (maculopapular rash)
• Hives
• Irritation at the injection site

Accidental injection of the medicine into the tissue around the vein can cause pain and lead to tissue damage.

You may experience one or more side effects. If you experience any side effects, inform your doctor or pharmacist.

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Ministry of Health,
Al. Jerozolimskie 181C, PL-02-222 Warsaw, Tel.: + 48 22 49-21-301, Fax: + 48 22 49-21-309,
Website: https://smz.ezdrowie.gov.pl
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 Detimedac

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. The expiry date refers to the last day of that month. Do not store above 25°C. Store in the outer carton in order to protect from light. Reconstituted Detimedac solution The reconstituted solution of Detimedac has been shown to be physically and chemically stable for 48 hours at 2-8°C, protected from light, and stored in a glass vial. From a microbiological point of view, the product should be used immediately. If not used immediately, the person administering the product is responsible for the storage conditions and storage time before administration, which normally should not exceed 24 hours at 2-8°C, unless prepared in controlled and validated aseptic conditions. Reconstituted and further diluted Detimedac solution The reconstituted and further diluted solution has been shown to be physically and chemically stable for 2 hours at 25°C in polyethylene containers and for 24 hours at 2-8°C, protected from light, in polyethylene containers and glass bottles, when reconstituted with water for injection and further diluted with 5% glucose solution or 0.9% sodium chloride solution. From a microbiological point of view, the solution should be used immediately after reconstitution and further dilution. Detimedac is for single use only. Any unused product or waste material should be disposed of in accordance with local requirements. The diluted infusion solution should be inspected; only clear solutions, practically free from particulate matter, are acceptable for use.

6. Contents of the pack and other information

What Detimedac contains

• The active substance is dacarbazine.
• The other ingredients are anhydrous citric acid and mannitol.

What Detimedac looks like and contents of the pack

Detimedac is a white or pale yellow powder in a glass vial of type I orange glass. Each vial of Detimedac 100 mg contains 100 mg of dacarbazine. Each vial of Detimedac 200 mg contains 200 mg of dacarbazine. After reconstitution, Detimedac contains 10 mg/ml of dacarbazine. 10 vials in a cardboard box.

Marketing authorization holder and manufacturer

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

Date of last revision of the leaflet: -------------------------------------------------------------------------------------------------------------------------

Information intended for healthcare professionals only:
Dacarbazine is a cytotoxic medicine. Before starting treatment, you should familiarize yourself with local guidelines for handling cytotoxic medicines. Containers containing dacarbazine should only be opened by trained personnel; as with other cytotoxic medicines, you should avoid exposure to the medicine. You should avoid exposure to cytotoxic medicines during pregnancy. The solution for administration should be prepared in a designated area; the necessary procedures should be performed over a washable tray or a single-use, absorbent paper covered with a protective film to prevent leakage. You should use appropriate protective eyewear, single-use gloves, face masks, and single-use aprons. Syringes and infusion sets should be assembled carefully to avoid leakage (it is recommended to use "luer lock" tips). After completing the work, you should carefully clean each surface that may have been contaminated and wash your hands and face. In case of accidental spillage, personnel should wear single-use gloves, face masks, protective eyewear, and single-use aprons and remove the spilled substance using absorbent material available for this purpose on site. The work surface should then be cleaned, and the contaminated material should be placed in a special bag or container for cytotoxic waste or sealed for incineration. Prepared solutions should be protected from light during administration (using light-protective infusion sets).