Detimedac 1000 mg

Package Leaflet: Information for the User

Detimedac 500 mg, powder for solution for infusion

Detimedac 1000 mg, powder for solution for infusion

(Dacarbazine)

Read all of this leaflet carefully before taking 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 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 Detimedac is and what it is 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 Detimedac is and what it is used for

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

• advanced malignant melanoma (skin cancer)
• Hodgkin's disease (cancer of the lymphatic system)
• soft tissue sarcoma (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 at the same time or within 3 weeks of Detimedac, or if you are given fotemustine.

Warnings and precautions

Before starting treatment with Detimedac, discuss this with your doctor or pharmacist. Before each dose of Detimedac, a blood test is performed to check if your blood cell count is sufficient for the administration of Detimedac. Your liver and kidney function will also be evaluated.

Detimedac with other medicines

Tell your doctor or pharmacist about all medicines you are taking, or have recently taken, and about any medicines you plan to take. It is not recommended to use any medicinal treatment without first informing your doctor, as there may be 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 metabolized by the liver enzyme system called cytochrome P450.
• Methoxsalen - used in 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).
• Cyclosporine or tacrolimus - these medicines may weaken the immune system.
• Fotemustine - Detimedac should not be used until at least one week after the administration of fotemustine to avoid lung damage.

During chemotherapy, avoid using 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 will check your blood clotting. The recommendations for vaccinations vary depending on the type of vaccine:

• Yellow fever vaccine - do not give the yellow fever vaccine to a patient being treated with Detimedac.
• Live vaccines - do not give live vaccines to a patient being treated with Detimedac, as Detimedac may lower immunity and increase the risk of severe infections.
• Inactivated vaccines - a patient being treated with Detimedac can be given inactivated vaccines.

Detimedac with food, drink, and alcohol

Do not drink alcohol during chemotherapy.

Pregnancy, breastfeeding, and fertility

Detimedac must not be given if you are pregnant, think you may be pregnant, or plan to have a child. Do not breastfeed during treatment with Detimedac. During treatment with Detimedac, use effective 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 on 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 given according to the doctor's instructions, by a specialist in oncology or hematology (the field of 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 given by a doctor or nurse through an intravenous infusion (into a vein) - the infusion will last from 20 to 30 minutes. Detimedac 500 mg and Detimedac 1000 mg powder should be dissolved in 50 ml of water for injection just before administration. The resulting solution should be diluted in 200-300 ml of isotonic sodium chloride solution or 5% glucose solution.

Dose of Detimedac

Your doctor will determine the dose to be given to you. The dose depends on the type of cancer and the stage of the disease, body surface area (m²), blood test results, and other anticancer medicines or therapies 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 therapies, and your response to Detimedac. If you have any questions about your treatment, ask your doctor, pharmacist, or nurse. Metastatic malignant melanoma
The recommended dose is 200-250 mg per m² of body surface area, once a day. This dose is given for 5 days in a row, every 3 weeks. The medicine is given as a rapid injection into a vein or a slow infusion into a vein, lasting 15-30 minutes.
Another option is to give a single large dose of 850-1000 mg per m² of body surface area, once every 3 weeks. This dose will be given as a slow infusion into a vein.
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 scheme). This dose will be given as a slow infusion into a vein.
Soft tissue sarcoma
The recommended dose is 250 mg per m² of body surface area, once a day. This dose is given for 5 days in a row, every 3 weeks. The medicine is given as a slow infusion into a vein, lasting 15-30 minutes.
You will also receive doxorubicin (this combination of medicines is called the ADIC scheme).

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 more data are available.

Overdose of Detimedac

Tell your doctor or nurse immediately 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 corrective measures may be taken, such as blood transfusion.
• Overdose can cause severe bone marrow damage (toxicity). It may lead to complete loss of bone marrow function (aplastic anemia). It may 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.

Tell your doctor immediately if you notice:

• signs of infection, such as sore throat and high temperature;
• 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 feelings of fainting;
• 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 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) Blood cell count changes 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 may 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 the 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 count of all blood cells (pancytopenia)
• Severe decrease in the count of a specific type of white blood cell (agranulocytosis)
• Severe allergic reactions (anaphylaxis) with symptoms such as: 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 outside the vein may cause pain and lead to tissue damage.

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

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety, Ministry of Health, via the online reporting system at [insert website URL]. Side effects can also be reported to the marketing authorization holder.

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 stated on the label and carton. The expiry date refers to the last day of the month. Do not store above 25°C. Store in the original package to protect from light. Reconstituted Detimedac solution

It has been demonstrated that freshly prepared (reconstituted) Detimedac solutions dissolved in water for injection remain 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 medicine should be used immediately after preparation. If not used immediately, the person responsible for administering the medicine is responsible for the storage conditions and storage time before administration, which should not exceed 24 hours at 2-8°C, unless prepared in controlled and sterile conditions. Reconstituted and further diluted Detimedac solution

It has been shown that the reconstituted and further diluted Detimedac solution remains stable for 24 hours when protected from light and stored at 2-8°C in polyethylene containers and glass bottles, and for 2 hours when stored at 25°C in polyethylene containers, and when water for injection is used for reconstitution and 5% glucose solution or 0.9% sodium chloride solution is used for further dilution. 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, as well as solutions that have changed appearance. The diluted infusion solution should be inspected; only clear solutions, practically free from particulate matter, are suitable 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 500 mg contains 500 mg of dacarbazine. After reconstitution and final dilution, Detimedac 500 mg contains 1.4-2.0 mg/ml of dacarbazine. Each vial of Detimedac 1000 mg contains 1000 mg of dacarbazine. After reconstitution and final dilution, Detimedac 1000 mg contains 2.8-4.0 mg/ml of dacarbazine. 1 vial 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, familiarize yourself with local guidelines for handling cytotoxic medicines. Vials containing dacarbazine should only be opened by trained personnel; as with other cytotoxic medicines, avoid exposure of staff to the medicine. 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. Use appropriate protective eyewear, single-use gloves, face masks, and single-use gowns. Syringes and infusion sets should be assembled carefully to avoid leakage (it is recommended to use "luer lock" ends). After finishing work, 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 gowns, and remove the spilled substance using an absorbent material available for this purpose on site. Then, clean the work surface and dispose of the contaminated material in a special bag or container for cytotoxic waste or seal it for incineration. Prepared solutions should be protected from light during administration (use light-protective infusion sets).