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
( Dacarbazinum )
Please read all of this leaflet carefully before this medicine is administered, 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. What you need to know 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 Administration of Detimedac

When not to administer Detimedac

• if the patient is allergic to dacarbazine or any of the other ingredients of this medicine (listed in section 6);
• if white blood cell or platelet counts are too low (leukopenia and/or thrombocytopenia);
• if the patient has severe liver or kidney disease;
• if the patient is pregnant or breastfeeding;
• concomitantly 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.
Prior to 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
Inform your doctor or pharmacist about all medicines currently used, recently used, or planned for use.
It is not recommended to start any medical treatment without first informing your doctor, due to the potential for interactions between Detimedac and other medicines.

In particular, inform your doctor or pharmacist if the patient is receiving any of the following treatments:

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

During chemotherapy, avoid using drugs that may damage the liver (e.g. diazepam, imipramine, ketoconazole, or carbamazepine).
The doctor will decide whether the patient should receive medications to improve 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 given to patients 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 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 administered if the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant.
Breastfeeding must not be performed 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 or operate machinery due to possible adverse effects on the central nervous system (brain and spinal cord) or due to possible nausea and vomiting. However, there is no reason to refrain from 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 access to equipment enabling regular monitoring of all clinical symptoms during and after treatment.

Dacarbazine is a light-sensitive substance. The physician or nurse administering the medicine will ensure appropriate handling and protection of dacarbazine from daylight.

Administration of Detimedac

Detimedac will be administered by a physician or nurse as an intravenous infusion lasting from 20 to 30 minutes.

Detimedac 500 mg and Detimedac 1000 mg powder for solution for infusion must be dissolved immediately before administration in 50 ml of water for injections. The resulting solution should then be diluted in 200–300 ml of isotonic sodium chloride solution or 5% glucose solution.

Dosage of Detimedac

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

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 the treatment, consult your physician, pharmacist, or nurse.

Metastatic skin cancer (metastatic malignant melanoma)

The recommended dose is 200–250 mg per m² of body surface area, administered once daily. This dose is given for 5 consecutive days every 3 weeks. The medicine is administered either as a rapid intravenous injection or as a slow intravenous infusion lasting 15–30 minutes.

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

Lymphatic system tumor (Hodgkin’s disease)

The recommended dose is 375 mg per m² of body surface area, administered 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, administered once daily. This dose is given 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 known as the ADIC regimen).

Patients with renal or hepatic impairment

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

Elderly patients

There are no special recommendations regarding 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.

Overdose of Detimedac

Inform your physician or nurse immediately if you suspect that a higher than recommended dose of Detimedac has been administered.

• 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 regarding the use of this medicine, consult your physician or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everybody 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 temperature;
• 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 in swallowing or breathing), or a feeling of fainting;
• yellowing of the skin and eyes due to liver problems;
• symptoms affecting the brain or nervous system, such as headaches, blurred vision, seizures, confusion, lethargy (drowsiness), or numbness and tingling of the face. All the above-mentioned 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 lowest values often observed only after 3–4 weeks.
• Loss of appetite (anorexia), nausea, vomiting (all the aforementioned symptoms may be severe).

Uncommon (may affect up to 1 in 100 people)

• Hair loss
• Increased skin pigmentation (discoloration)
• Skin sensitivity to light (photosensitivity)
• Flu-like symptoms with feeling of exhaustion, chills, fever, and muscle pain. These symptoms may occur during administration of the medicine or a few days after administration. 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)
• Marked decrease in granulocytes, a specific type of white blood cells (agranulocytosis)
• Severe allergic reactions (anaphylaxis) manifested by: drop in blood pressure, swelling of the hands, feet, ankles, face, lips, mouth or throat, which may lead to difficulty in swallowing or breathing, rapid heartbeat, urticaria, and generalized itching or redness of the skin
• Headaches
• Visual disturbances
• Confusion
• Lethargy (drowsiness)
• Seizures (convulsive attacks)
• Unusual sensations in the face (facial paraesthesia), numbness, and sudden reddening of the facial skin immediately 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. If these complications are suspected, the doctor will determine appropriate treatment for the patient.
• Increased liver enzyme activity
• Skin redness (erythema)
• Skin eruptions (maculopapular rash)
• Urticaria
• Irritation at the site of drug administration

Accidental injection of the medicine into the tissue surrounding the vein may cause pain and lead to tissue damage.
One or more adverse reactions may occur. If any adverse reactions occur, the doctor or pharmacist should be informed.
Reporting 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 Reactions of Medicinal Products at 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 may also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more 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) solutions of Detimedac, dissolved in water for injections, maintain physical and chemical stability for 48 hours at 2–8°C when protected from light and stored 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 sterile conditions.

Detimedac solution after reconstitution and further dilution
It has been shown that Detimedac solution, after reconstitution and further dilution, 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, provided that water for injections was used for reconstitution and either 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 should any 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 pack and other information

What Detimedac contains

• The active substance is dacarbazine.
• The other ingredients (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 vial made of orange type I 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 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 for healthcare professionals only:
Dacarbazine is an antineoplastic agent. Prior to administration, local guidelines regarding handling procedures for 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 infusion solution must be prepared in a designated area; procedures should be carried out over a washable tray or on absorbent, impermeable-backed protective paper.
Appropriate protective goggles, disposable gloves, face masks, and disposable gowns must be worn.
Syringes and infusion sets should be assembled carefully to prevent leakage (use of "luer lock" connectors is recommended).
After completion of work, all potentially contaminated surfaces must be thoroughly cleaned, and hands and face must be washed.
In case of spillage, personnel must wear disposable gloves, face masks, protective goggles, and disposable gowns, and the spilled material must be removed using absorbent material specifically designated for this purpose. The work surface must then be cleaned, and contaminated materials must be placed in a special bag or container for cytotoxic waste or securely sealed for incineration.
Prepared solutions must be protected from light during administration (use of light-protective infusion sets).