Detimedac 200 mg

Leaflet attached to the packaging: information for the user

Detimedac 100 mg, powder for solution for injection / infusion

Detimedac 200 mg, powder for solution for injection / infusion

(Dacarbazine)

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Detimedac and what is it used for
• 2. Important information before taking Detimedac
• 3. How to take Detimedac
• 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 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 (malignant lymphoma)
• soft tissue sarcoma (malignant tumor of muscle tissue, fat tissue, fibrous tissue, blood vessels or other supporting tissues). Detimedac may be used in combination with other cytotoxic medicines.

2. Important information before taking Detimedac

When not to take Detimedac

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

Warnings and precautions

Before starting treatment with Detimedac, the patient should discuss it with their doctor or pharmacist.
Before each administration of Detimedac, a blood test is performed to assess whether the patient has a sufficient number of blood cells to receive the medicine. The liver and kidney function are also evaluated.

Detimedac and other medicines

The patient should inform their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
It is not recommended to take any medicinal therapy without first informing the doctor, as there may be interactions between Detimedac and other medicines.
In particular, the patient should inform their doctor or pharmacist if they are being treated with any of the following therapies:

• 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 earlier than one week after administration of fotemustine to avoid lung damage.

During chemotherapy, the patient should avoid taking medicines that may damage the liver (e.g., diazepam, imipramine, ketoconazole, or carbamazepine).
The doctor will decide whether the patient should take medicines that improve blood circulation and will check the patient's blood clotting.
Vaccination recommendations vary depending on the type of vaccine:

• Yellow fever vaccine - the patient should not receive the yellow fever vaccine while being treated with Detimedac.
• Live vaccines - the patient should not receive live vaccines while being treated with Detimedac, as the medicine may lower the immune system and increase the risk of severe infections.
• Inactivated vaccines - the patient may receive inactivated or killed vaccines while being treated with Detimedac.

Detimedac with food, drink, and alcohol

The patient should not consume alcohol during chemotherapy.

Pregnancy, breastfeeding, and fertility

Detimedac should not be administered if the patient is pregnant, suspects they may be pregnant, or plans to have a child.
The patient should not breastfeed during treatment with Detimedac.
During treatment with Detimedac, the patient should 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 the patient's ability to drive and 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 the patient experiences dizziness and feels unsteady.

3. How to take Detimedac

This medicine should always be taken according to the doctor's instructions, under the supervision of a specialist experienced in cancer treatment 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 it 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 injections immediately before administration, and Detimedac 200 mg powder will be dissolved in 20 ml of water for injections.
If the medicine is administered as an intravenous infusion, the solution will be further diluted.

Dose of Detimedac

The doctor will determine the dose to be administered to the patient. The dose depends on the type of cancer and the stage of the disease, body surface area (m²), blood morphology results, and other cancer medicines or therapies used at the same time.
The treating doctor will determine the duration of treatment with this medicine for each patient.
The doctor may change the dose and frequency of administrationbased on blood test results, the patient's overall condition, other therapies, and the patient's response to Detimedac. If the patient has any questions about treatment, they should consult their 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 a day. 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.
Lymphoma (Hodgkin's disease)
The recommended dose is 375 mg per m² of body surface area, every 15 days. The patient will also receive doxorubicin, bleomycin, and vinblastine (this combination of medicines is called the ABVD scheme). 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 a day. This dose is administered for 5 consecutive days every 3 weeks. The medicine is administered as a slow intravenous infusion lasting 15-30 minutes.
The patient will also receive doxorubicin (this combination is called the ADIC scheme).

Patients with kidney or liver disorders

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

Elderly patients

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

Use in children

Until additional data are available, there are no recommendations for the use of dacarbazine in children.

Administration of a higher dose of Detimedac than recommended

The patient should immediately inform their doctor or nurse if they think they have received a higher dose of Detimedac than recommended.

• In case of suspected overdose, the patient's 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.

In case of any further doubts about the use of this medicine, the patient should consult their doctor or pharmacist.

4. Possible side effects

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

The patient should immediately inform their doctor if they notice:

• infection symptoms such as sore throat and high fever;
• unusual bruising or bleeding;
• severe 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 of the face.

All of the above symptoms are serious side effects. The patient may need immediate 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) 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 administration of the medicine and may recur during subsequent administration of dacarbazine.
• Infections

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

• Decreased count of all blood cells (pancytopenia)
• Significant decrease in the count 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 heart rate, 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 may be life-threatening. In case of suspected complications, the doctor will determine the appropriate treatment for the patient.
• Increased liver enzyme activity
• Redness of the skin (erythema)
• Skin rashes (papular rash)
• Hives
• Irritation at the injection site

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

The patient may experience one or more side effects. If the patient experiences any side effects, they should inform their doctor or pharmacist.

Reporting side effects

If the patient experiences any side effects, including those not listed in the leaflet, they should inform their doctor or pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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,
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Detimedac

The medicine should be stored out of 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 outer packaging to protect from light.
Detimedac solution after reconstitution
It has been demonstrated that freshly prepared (after reconstitution) Detimedac solutions dissolved in water for injections 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 administering the medicine is responsible for the storage time and conditions before administration, and the storage time should not normally exceed 24 hours at 2-8°C, unless prepared in controlled and validated aseptic conditions.
Detimedac solution after reconstitution and further dilution
It has been shown that the solution after reconstitution and further dilution remains chemically and physically stable for 2 hours at 25°C in polyethylene containers and for 24 hours at 2-8°C in polyethylene containers and glass bottles, when reconstituted with water for injections 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 intended for single use.
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 type I orange glass vial.
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, local guidelines for handling cytotoxic medicines should be consulted.
Containers containing dacarbazine should only be opened by trained personnel; as with other cytotoxic medicines, exposure of personnel to the medicine should be avoided.
Exposure to cytotoxic medicines should be avoided during pregnancy. The solution for administration should be prepared in a designated area; appropriate procedures should be performed over a washable tray or a single-use, absorbent paper covered with a protective film to prevent leakage.
Appropriate protective eyewear, single-use gloves, face masks, and single-use aprons should be used.
Syringes and infusion sets should be assembled carefully to avoid leakage (it is recommended to use "luer lock" tips).
After completing the work, each surface that may have been contaminated should be carefully cleaned, and hands and face should be washed.
In case of 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 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).