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
( Dacarbazinum )
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Detimedac is and what it is used for
2. Important information before receiving Detimedac
3. How to use Detimedac
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 medicines called cytotoxic agents. These medicines affect the growth of cancer cells.
Detimedac is used in the treatment of cancers such as:

• Advanced malignant melanoma (a malignant skin tumour)
• Hodgkin's disease (a malignant disorder of the lymphatic system)
• Soft tissue sarcoma (a malignant tumour of muscle tissue, fatty tissue, fibrous tissue, blood vessels, or other supportive tissues). Detimedac may be used in combination with other cytotoxic medicines.

2. Important information before administering Detimedac

When not to give Detimedac

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

Warnings and precautions
Before starting treatment with Detimedac, discuss this with your doctor or pharmacist.
Before each administration of Detimedac, a blood test is performed to assess whether the patient's blood cell count is sufficient for administration of Detimedac. Liver and kidney function are also evaluated.

Detimedac and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
It is not recommended for the patient to start any medicinal therapy without first informing the doctor, due to the risk of interactions between Detimedac and other medicines.
In particular, tell your doctor or pharmacist if the patient is being treated with any of the following therapies:

• Radiotherapy or other medicines used to inhibit the growth of tumours (chemotherapy). The use of these medicines together with Detimedac may intensify harmful effects on the bone marrow.
• Other medicines metabolized by the hepatic enzyme system known as cytochrome P450.
• Methoxypsoralen – used in skin disorders such as psoriasis and eczema. The use of Detimedac together with methoxypsoralen may increase sensitivity to sunlight (photosensitivity).
• Phenytoin – concomitant use of Detimedac and phenytoin increases the risk of seizures (convulsions).
• Cyclosporine or tacrolimus – these medicines may suppress the immune system.
• Fotemustine – Detimedac must not be administered earlier than one week after fotemustine administration to avoid lung damage.

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

• Yellow fever vaccine – the yellow fever vaccine should not be administered to patients being treated with Detimedac.
• Live vaccines – live vaccines should not be administered to patients being treated with Detimedac, as Detimedac may reduce immunity and increase susceptibility to severe infections.
• Inactivated vaccines – inactivated or killed vaccines may be administered to patients being treated with Detimedac.

Detimedac with food, drink, and alcohol
Alcohol should not be consumed during chemotherapy.

Pregnancy, breastfeeding, and effects on fertility
Detimedac must not be given if the patient is pregnant, suspects she may be pregnant, or is planning to have a child.
Breastfeeding must not be undertaken during treatment with Detimedac.
Effective contraception must be used during treatment with Detimedac. Men should continue using effective contraception for at least 6 months after completion of treatment with Detimedac.

Driving and operating machinery
Dacarbazine may affect the ability to drive and operate machinery due to the potential for adverse effects on the central nervous system (affecting the brain and spinal cord) or due to possible nausea and vomiting. However, there is no reason to discontinue driving or operating machinery between treatment cycles, unless the patient experiences dizziness or feels unsteady.

3. How to use Detimedac

This medicine should always be used in accordance with the recommendations of a specialist physician experienced in anticancer therapy or hematology (the branch of medicine dealing with blood disorders), who has equipment available to monitor all clinical symptoms regularly during and after treatment.

Dacarbazine is light-sensitive. The doctor or nurse administering the medicine will ensure appropriate administration of dacarbazine 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 (intravenous drip) – the infusion will last 15 to 30 minutes.

Detimedac 100 mg powder will be dissolved just before administration in 10 ml of water for injections; in the case of Detimedac 200 mg powder, it will be dissolved in 20 ml of water for injections. If Detimedac is administered as an intravenous infusion, the solution will be further diluted.

Dosage of Detimedac

The physician will determine the dose to be administered to the patient. The dose depends on the type of tumor and the stage of the disease, body surface area (m²), blood count results, and other concurrently administered anticancer drugs or therapies. The treating physician will determine, for each individual patient, the duration of treatment with this medicine.

The physician may adjust the dose and frequency of administration depending on blood test results, the patient's general condition, other therapies, and the patient's response to Detimedac. If you have any questions about your treatment, consult your doctor, pharmacist, or nurse.

Metastatic skin cancer (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 given as a rapid intravenous injection or slow intravenous infusion lasting 15–30 minutes.

Alternatively, a single high dose of 850–1000 mg per m² of body surface area may be administered once every 3 weeks. This dose will be given as a slow intravenous infusion.

Lymphatic system cancer (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 is known as the ABVD regimen). This dose will be administered as a slow intravenous infusion.

Soft tissue tumors (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 given as a slow intravenous infusion lasting 15–30 minutes.

The patient will also receive doxorubicin (this combination is known as the ADIC regimen).

Patients with kidney or liver impairment

In patients with mild or moderate kidney or liver impairment, dose reduction is usually not necessary. In patients with both kidney and liver impairment, metabolism and elimination of the drug from the body may take longer. The physician may recommend administering a lower dose to the patient.

Elderly patients

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

Use in children

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

Administration of a higher than recommended dose of Detimedac

Inform your doctor or nurse immediately if you think you have been given more than the recommended dose of this medicine.

• In case of suspected overdose, blood cell counts will be monitored and corrective measures such as blood transfusion may be necessary.
• Overdose may cause severe bone marrow damage (myelotoxicity). It may lead to complete loss of bone marrow function (aplastic anemia). This may occur as a delayed reaction, even up to two weeks after administration.

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

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
The doctor will inform the patient about the possibility of adverse reactions and will explain the risks and benefits associated with treatment.
The patient should immediately inform the doctor if any of the following symptoms occur:

• signs of infection such as sore throat and high fever;
• unusual bruising or bleeding;
• severe fatigue;
• persistent or severe diarrhoea or vomiting;
• severe allergic reactions – sudden rash with itching, swelling of the hands, feet, ankles, face, lips, mouth or throat (which may lead to difficulty swallowing or breathing), or a feeling of fainting;
• yellowing of the skin and eyes due to liver problems;
• neurological or brain-related symptoms such as headaches, blurred vision, seizures, confusion, lethargy (drowsiness), or numbness and tingling of the face.

All of the above symptoms are serious adverse reactions. The patient may require immediate medical attention.
Other adverse reactions may also occur:
Common (may affect up to 1 in 10 people)

• Decrease in red blood cells (anaemia)
• Decrease in white blood cells (leukopenia)
• Decrease in platelets (thrombocytopenia). Changes in blood cell counts are dose-dependent and delayed, with the lowest values often observed only after 3–4 weeks.
• Loss 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 (hyperpigmentation)
• Skin sensitivity to light (photosensitivity)
• Flu-like symptoms with feelings of exhaustion, chills, fever, and muscle pain. These symptoms may occur during or several days after administration of the medicine. They may also recur during subsequent administrations of 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 cells (agranulocytosis)
• Severe allergic reactions (anaphylaxis) presenting as: drop in blood pressure, swelling of the hands, feet, ankles, face, lips, mouth or throat, which may lead to difficulty swallowing or breathing, rapid heartbeat, urticaria and generalized itching or redness of the skin
• Headaches
• Vision disturbances
• Confusion
• Lethargy (drowsiness)
• Seizures (convulsions)
• Unusual sensations in the face (facial paraesthesia), numbness, and sudden redness of the facial skin shortly after injection.
• Diarrhoea
• 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 suspicion of these complications, the doctor will determine appropriate treatment for the patient.
• Increased liver enzyme activity
• Redness of the skin (erythema)
• Skin eruptions (maculopapular rash)
• Urticaria
• Irritation at the site of administration

Accidental injection of the medicine into the tissue surrounding a vein may cause pain and lead to tissue damage.
One or more adverse reactions may occur. If any adverse reactions occur, the patient should inform the doctor or pharmacist.
Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, the patient should inform the doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting of adverse reactions enables further collection of information on the safety of the 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 stated on the label and carton. The expiry date refers to the last day of the stated 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, maintain physical and chemical stability for 48 hours when stored at 2–8°C protected from light and kept in a glass vial.
From a microbiological standpoint, 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 prior to administration; storage should generally not exceed 24 hours at 2–8°C, unless the solution was prepared under controlled and validated aseptic conditions.

Detimedac solution after reconstitution and further dilution
It has been shown that the solution after reconstitution and further dilution maintains chemical and physical stability for 2 hours when stored at 25°C in polyethylene containers, and for 24 hours when protected from light and stored at 2–8°C in polyethylene containers and glass bottles, provided that water for injections was used for reconstitution and 5% glucose solution or 0.9% sodium chloride solution was used for further dilution.
From a microbiological standpoint, the solution should be used immediately after reconstitution and further dilution.

Detimedac is intended for single use only.
Any unused portions of the medicinal product should be discarded, as well as solutions that have changed in appearance. The diluted infusion solution should be inspected visually; only clear solutions, practically free from particulate matter, should be used.

6. Contents of the package and other information

What Detimedac contains

• The active substance is dacarbazine.
• The other components (excipients) 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 amber 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 carton.

Marketing Authorisation 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

Information intended exclusively for medical professionals:

Dacarbazine is an antineoplastic agent. Prior to initiating treatment, local guidelines regarding handling of cytotoxic drugs should be consulted.
Containers containing dacarbazine must be opened only by trained personnel; as with other cytotoxic drugs, exposure of personnel to the drug should be avoided. Exposure to cytotoxic drugs during pregnancy should be avoided. The solution for administration must be prepared in a designated area; appropriate procedures should be carried out over a washable tray or disposable absorbent paper covered with a protective, impermeable foil.
Appropriate protective goggles, disposable gloves, face masks, and disposable gowns must be worn.
Syringes and infusion sets must be assembled carefully to prevent leakage (use of Luer-lock connectors is recommended).
After completion of work, any surface that may have become contaminated must be thoroughly cleaned, and hands and face must be washed.
In the event of spillage, personnel should put on disposable gloves, face masks, protective goggles, and disposable gowns, and the spilled material should be removed using absorbent material specifically designated for this purpose. The work surface should then be cleaned, and the contaminated material placed in a special bag or container for cytotoxic waste, or securely sealed for incineration.
Prepared solutions must be protected from light exposure, including during administration (use of light-protective infusion sets).