Dacarbazine medac

Package leaflet: Information for the patient

Dacarbazina medac 100 mg powder for injectable solution or for infusion, 200 mg powder for injectable solution or for infusion

Dacarbazina
Equivalent medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Dacarbazina medac is and what it is used for
2. What you need to know before receiving Dacarbazina medac
3. How to use Dacarbazina medac
4. Possible side effects
5. How to store Dacarbazina medac
6. Contents of the pack and other information

1. What Dacarbazina medac is and what it is used for

Dacarbazine belongs to a group of medicines known as cytostatic agents, which interfere with
the growth of cancer cells.
Dacarbazina medac has been prescribed by your doctor for the treatment of cancer, specifically:

• advanced malignant melanoma (skin cancer)
• Hodgkin's disease (cancer of the lymphatic tissues)
• soft tissue sarcoma (cancer of muscle, fat, fibrous tissue, blood vessels, or other types of supporting body tissue). Dacarbazina medac may be used in combination with other cytostatic agents.

2. What you need to know before receiving Dacarbazina medac

Do not receive treatment with Dacarbazina medac

• if you are allergic to dacarbazine or to any of the other ingredients of this medicine (listed in section 6)
• if you have abnormally low levels of white blood cells and/or platelets ( leucopenia and/or thrombocytopenia )
• if you have severe liver or kidney disease
• if you are pregnant or breastfeeding.

Warnings and precautions
Talk to your doctor or pharmacist before receiving Dacarbazina medac.
Before each administration of this medicine, blood tests will be performed to check that you have an adequate number of blood cells. Your liver and kidney function will also be monitored.
You must not receive live vaccines while taking Dacarbazina medac, because Dacarbazina medac can weaken the immune system and increase the risk of developing a serious infection.
You must not use fotemustine during treatment with Dacarbazina medac.
Other medicines and Dacarbazina medac
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
It is not advisable to use other medical treatments without informing your doctor, as Dacarbazina medac may interact with other medicines.
In particular, inform your doctor or pharmacist if you are using or receiving any of the following treatments:

• Radiotherapy or other medicines to reduce tumour growth (chemotherapy). Using these medicines together with Dacarbazina medac may increase bone marrow damage.
• Other medicines metabolized by a liver enzyme system called cytochrome P450.
• Methoxypsoralen (used for skin conditions such as psoriasis and eczema) – taking Dacarbazina medac with methoxypsoralen may increase sensitivity to sunlight (photosensitivity).
• Phenytoin (used to treat seizures) – using Dacarbazina medac and phenytoin together may increase the risk of seizures.
• Cyclosporine or tacrolimus (used to reduce the body's immune reactions) – these medicines may weaken the immune system.
• Fotemustine (used to treat skin cancer) – using Dacarbazina medac and fotemustine together may cause lung damage.
• Medicines that may cause liver damage, e.g. diazepam (used to treat anxiety, muscle spasms and seizures), imipramine (used to treat symptoms of depression), ketoconazole (used to treat fungal infections), carbamazepine (used to prevent epileptic seizures, relieve certain types of pain or control mood disorders) should be avoided during chemotherapy.
• Anticoagulants (medicines used to prevent blood clots) – your doctor will decide whether it is appropriate for you to receive these medicines and will perform tests to monitor your blood's clotting tendency.

You must not receive live vaccines while you are receiving Dacarbazina medac and for 3 months after completing treatment with Dacarbazina medac, because Dacarbazina medac can weaken the immune system and increase the risk of developing a serious infection.
You may receive a "killed" or inactivated vaccine while taking Dacarbazina medac.
Dacarbazina medac with food, drinks and alcohol
You must not consume alcoholic beverages during chemotherapy.
Pregnancy, breastfeeding and fertility
Dacarbazina medac must not be administered if you are pregnant, suspect you are pregnant, or are planning a pregnancy.
Do not breastfeed during treatment with Dacarbazina medac.
You must use effective contraception during treatment with Dacarbazina medac. Men must continue to use effective contraception for at least 6 months after stopping treatment with Dacarbazina medac.
If you plan to become pregnant or to breastfeed, consult your doctor first.
Driving and using machines
This medicine may affect your ability to drive or use machinery due to effects on the central nervous system (effects on the brain and nerves) or due to nausea and vomiting. However, between treatment cycles, you may drive or use machinery unless you experience dizziness or feel unsteady.

3. How to use Dacarbazina medac

This medicine will be administered to you under the supervision of a specialist doctor in oncology (cancer treatment) or haematology (the study of blood diseases). You will be kept under regular observation during and after treatment to detect any signs of adverse effects.

Dacarbazine is a photosensitive substance. The doctor or nurse administering this medicine will ensure you are protected from exposure to daylight during administration.

Amount of Dacarbazina medac administered

Your doctor will calculate the dose to be administered to you. This will depend on the type and stage of cancer, your body surface area (m²), your blood cell count, and any other anticancer medicines or therapies you are receiving. Your treating doctor will also individually determine the duration of treatment with this medicine.

Your doctor may adjust the dose and frequency of administration based on blood test results, your general health condition, additional therapies, and your response to this medicine. If you have any doubts about your treatment, consult your doctor, nurse, or pharmacist.

Skin cancer (metastatic malignant melanoma)

The usual dose is 200 – 250 mg per m² of body surface area, once daily. You will receive this dose for 5 consecutive days every 3 weeks. The dose will be administered as a rapid intravenous injection or as a slow intravenous infusion lasting 15 – 30 minutes.

Alternatively, you may receive a higher dose (850 mg per m² of body surface area) every 3 weeks, administered as a slow intravenous infusion.

Lymphatic tissue cancer (Hodgkin's disease)

The usual dose is 375 mg per m² of body surface area, every 15 days. You will also be given medicines called doxorubicin, bleomycin, and vinblastine (this combination is known as the ABVD regimen), administered as slow intravenous infusions.

Cancer of muscle, fat, fibrous tissue, blood vessels, and other supportive tissues of the body (soft tissue sarcoma)

The usual dose is 250 mg per m² of body surface area, once daily. You will receive this dose for 5 consecutive days every 3 weeks, administered as a slow intravenous infusion lasting 15 – 30 minutes.

You will also be administered a medicine called doxorubicin (this combination is known as the ADIC regimen).

Patients with kidney or liver problems

If you have mild or moderate kidney or liver problems, it is usually not necessary to reduce the dose of this medicine. If you have problems affecting both the kidneys and the liver, your body will take longer to process and eliminate the medicine. Your doctor may prescribe you a reduced dose of this medicine.

Use in children

Specific recommendations for the use of this medicine in children cannot be provided until further data become available.

If you have been given more Dacarbazina medac than you should have

Administration of an excessive amount of Dacarbazina medac may cause a severe reduction in blood cell counts. This could lead to complete loss of bone marrow function. Possible symptoms include signs of infection, bruising or bleeding due to increased bleeding tendency, or fatigue, and these may appear up to 2 weeks later.

If you think you have been given too much Dacarbazina medac, inform your doctor or nurse immediately.

Your blood cell count will be monitored and supportive measures such as blood transfusions may be required.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them. Your doctor will explain these to you, outlining the risks and benefits of the treatment.
Contact your doctor immediately if you notice any of the following:

• signs of infection such as sore throat and high fever
• unusual bruising or bleeding
• extreme tiredness
• persistent or severe vomiting or diarrhoea
• severe allergic reaction; you may develop a sudden rash with itching, swelling of hands, feet, ankles, face, lips, mouth or throat (possibly causing difficulty swallowing or breathing), and feel faint
• yellowing of the skin and eyes due to liver problems
• signs of brain or nerve problems such as headache, vision impairment, seizures, confusion, lethargy, or numbness and tingling of the face
• Severe liver disease due to blockage of the liver's blood vessels (veno-occlusive disease [VOD] or Budd-Chiari syndrome) with destruction of liver cells (hepatic necrosis), which may be fatal. If such complications are suspected, your doctor will decide on the appropriate treatment for you.

These are all serious side effects that may require immediate medical attention.
Other side effects listed below may also occur:
Common (may affect up to 1 in 10 people)

• Decrease in the number of red blood cells (anaemia)

• Decrease in the number of white blood cells (leucopenia)

• Decrease in the number of platelets (thrombocytopenia). Changes in blood counts are dose-dependent and delayed in onset; the lowest values are often observed only after 3–4 weeks.

• Loss of appetite (anorexia), nausea, and vomiting (all of which may be severe)
  Uncommon (may affect up to 1 in 100 people)

• Hair loss (alopecia)

• Increased skin pigmentation (hyperpigmentation)

• Skin sensitivity to light (photosensitivity)

• Flu-like symptoms such as fatigue, chills, fever, and muscle pain. These symptoms may occur during administration of the medicine or a few days afterwards. They may also recur with subsequent doses of dacarbazine.

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

• Decrease in the number of all blood cells (pancytopenia)

• Severe decrease in the number of granulocytes, a specific type of white blood cell (agranulocytosis)

• Severe allergic (anaphylactic) reaction, which may present, for example, as a drop in blood pressure, swelling of hands, feet, ankles, face, lips, mouth and throat causing difficulty in swallowing or breathing, rapid pulse, hives and widespread itching or skin redness

• Headache

• Vision impairment

• Confusion

• Lethargy

• Seizures (convulsions)

• Altered facial sensation (facial paraesthesia), numbness and redness of the face shortly after injection

• Diarrhoea

• Increased liver enzymes

• Impaired kidney function

• Skin redness (erythema)

• Skin rashes (maculopapular exanthema)

• Hives

• Irritation at the site of administration

If this medicine is accidentally injected into the tissue around the vein, pain and tissue damage may occur.
One or more of these symptoms may occur. If you experience any side effect,
including those not listed in this leaflet, consult your doctor or pharmacist.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. You may also report side effects directly via the website: http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dacarbazina medac

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 the carton after "Exp.". The expiry date refers to the last day of that month.
Do not store above 25°C. Keep the vial in the outer packaging to protect the medicine from light.
The shelf life of the medicine under these conditions is 3 years.
It has been demonstrated that freshly prepared (reconstituted) solutions of Dacarbazina medac remain stable for 24 hours when stored at 20°C and protected from light. From a microbiological standpoint, the product should be used immediately. Otherwise, the storage times and conditions prior to use are the responsibility of the user and should generally not exceed 24 hours at 2–8°C, unless reconstitution has been carried out under controlled and validated aseptic conditions.
The reconstituted and further diluted solution must be used immediately.
Dacarbazina medac is for single use only.
The physician must discard any unused content after administration and any solutions showing visible changes in appearance. After dilution, the infusion solution should be visually inspected by the physician, and only clear, particle-free solutions should be used.

6. Package contents and other information

What Dacarbazina medac contains

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

Description of the appearance of Dacarbazina medac and contents of the pack
Dacarbazina medac is a white or pale yellow powder contained in amber glass vials (type I, European Pharmacopoeia).
Each single-dose vial of Dacarbazina medac 100 mg contains 100 mg of dacarbazine (dacarbazine citrate).
Each single-dose vial of Dacarbazina medac 200 mg contains 200 mg of dacarbazine (dacarbazine citrate).
After reconstitution, Dacarbazina medac contains 10 mg/mL of dacarbazine.
The vials of Dacarbazina medac are packed in boxes containing 10 vials each.

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

This medicinal product is authorised in the European Economic Area Member States under the following names:
Austria Dacarbazina medac 100 mg/200 mg, Powder for solution for injection/infusion
Belgium DACARBAZINE MEDAC 100 mg/200 mg, powder for solution for injection/infusion
DACARBAZINE MEDAC, poudre pour solution injectable/pour perfusion
DACARBAZINE MEDAC, Pulver zur Herstellung einer Injektions-/Infusionslösung
Denmark Dacarbazine medac 100 mg/200 mg, powder for solution for injection/infusion
Germany Detimedac 100 mg/200 mg, Powder for solution for injection/infusion
Ireland Dacarbazine medac 200 mg, powder for solution for injection/infusion
Italy Dacarbazina medac 100 mg/200 mg, powder for solution for injection/infusion
Netherlands Dacarbazine medac 100 mg/200 mg, powder for solution for injection/infusion
Portugal Dacarbazine medac 100 mg/200 mg, powder for solution for injection/infusion
Sweden Dacarbazine medac 100 mg/200 mg, powder for solution for injection/infusion
United Kingdom Dacarbazine medac 100 mg/200 mg, powder for solution for injection/infusion

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The following information is intended exclusively for physicians or healthcare professionals:
Recommendations for safe handling
Dacarbazine is an antineoplastic agent and must be handled according to standard procedures for cytotoxic drugs with mutagenic, carcinogenic and teratogenic effects. Before proceeding, consult local guidelines regarding cytotoxic agents.
Dacarbazine should only be handled by trained personnel, and precautions must be taken to avoid exposure, as with all cytotoxic agents. Handling of cytotoxic drugs should generally be avoided during pregnancy. The solution for administration must be prepared in a designated area, working on a washable tray or on absorbent paper with a plastic backing, wearing appropriate eye protection, gloves, disposable gown, and face mask. Syringes and infusion sets must be assembled carefully to prevent leakage (use of Luer-lock adapters is recommended).
After preparation, any exposed surfaces must be thoroughly cleaned, and hands and face must be washed.
In case of spillage, personnel must wear gloves, face mask, eye protection, and disposable gown, and collect the spilled material using absorbent material specifically intended for this purpose, applied to the affected area. The area must then be cleaned, transferring all contaminated material into a bag or container for cytotoxic waste, or sealed for incineration.

Preparation for intravenous administration
Dacarbazine solutions must be prepared immediately before use.
Dacarbazine is light-sensitive. During administration, the infusion container and administration set must be protected from daylight, e.g., by using light-resistant PVC infusion sets. Standard infusion sets should be wrapped, e.g., in UV-resistant film.

a) Preparation of Dacarbazina medac 100 mg:
Under aseptic conditions, transfer 10 mL of water for injections into the vial and shake until a solution is obtained. The freshly prepared solution, containing 10 mg/mL of dacarbazine (solution density: \ρ = 1.007 g/mL), is administered by slow injection.
For preparing Dacarbazina medac 100 mg for intravenous infusion, the freshly prepared solution should be further diluted with 200–300 mL of 0.9% sodium chloride solution or 5% glucose solution for infusion. This solution is administered as a short-term infusion over 15–30 minutes.

b) Preparation of Dacarbazina medac 200 mg:
Under aseptic conditions, transfer 20 mL of water for injections into the vial and shake until a solution is obtained. The freshly prepared solution, containing 10 mg/mL of dacarbazine (solution density: \ρ = 1.007 g/mL), is administered by slow injection.
For preparing Dacarbazina medac 200 mg for intravenous infusion, the freshly prepared solution should be further diluted with 200–300 mL of 0.9% sodium chloride solution or 5% glucose solution for infusion. This solution is administered as a short-term infusion over 15–30 minutes.

Dacarbazina medac 100 mg (200 mg) is for single use only.
After dilution, the infusion solution must be inspected visually; only clear, particle-free solutions should be used. Do not use the solution if particulate matter is present.
Any remaining contents after use and solutions showing changes in visual appearance must be discarded.
Unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.

Patient Information Leaflet

Dacarbazina medac 500 mg powder for solution for infusion, 1000 mg powder for solution for infusion

Dacarbazina
Equivalent medicine
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Dacarbazina medac is and what it is used for
2. What you need to know before receiving Dacarbazina medac
3. How to use Dacarbazina medac
4. Possible side effects
5. How to store Dacarbazina medac
6. Contents of the pack and other information

1. What Dacarbazina medac is and what it is used for

Dacarbazine belongs to a group of medicines known as cytostatic agents, which interfere with
the growth of tumour cells.
Dacarbazina medac has been prescribed by your doctor for the treatment of cancer, specifically:

• advanced malignant melanoma (skin cancer)
• Hodgkin's disease (cancer of the lymphatic tissues)
• soft tissue sarcoma (cancer of muscle, fat, fibrous, blood vessel, or other supportive body tissues). Dacarbazina medac may be used in combination with other cytostatic agents.

2. What you need to know before receiving Dacarbazina medac

Do not receive treatment with Dacarbazina medac

• if you are allergic to dacarbazine or to any of the other ingredients of this medicine (listed in section 6)
• if you have too low a number of white blood cells and/or platelets ( leucopenia and/or thrombocytopenia )
• if you have severe liver or kidney disease
• if you are pregnant or breastfeeding.

Warnings and precautions
Talk to your doctor or pharmacist before receiving Dacarbazina medac.
Before each administration of this medicine, blood tests will be performed to check for a sufficient number of blood cells. Your liver and kidney function will also be monitored.
You must not receive live vaccines while taking Dacarbazina medac, because Dacarbazina medac can weaken the immune system and increase the risk of developing a serious infection.
You must not use fotemustine during treatment with Dacarbazina medac.

Other medicines and Dacarbazina medac
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
It is not advisable to use other medical treatments without informing your doctor, as Dacarbazina medac may interact with other medicines.
In particular, inform your doctor or pharmacist if you are using or receiving any of the following treatments:

• Radiotherapy or other medicines to reduce tumor growth (chemotherapy). Using these medicines together with Dacarbazina medac may increase bone marrow damage.
• Other medicines metabolized by a liver enzyme system called cytochrome P450.
• Methoxypsoralen (used for skin conditions such as psoriasis and eczema) – taking Dacarbazina medac with methoxypsoralen may increase sensitivity to sunlight (photosensitivity).
• Phenytoin (used to treat seizures) – using Dacarbazina medac and phenytoin together may increase the risk of seizures.
• Cyclosporine or tacrolimus (used to reduce the body's immune reactions) – these medicines may weaken the immune system.
• Fotemustine (used to treat skin cancer) – using Dacarbazina medac and fotemustine together may cause lung damage.
• Medicines that may cause liver damage, e.g. diazepam (used to treat anxiety, muscle spasms, and seizures), imipramine (used to treat symptoms of depression), ketoconazole (used to treat fungal infections), carbamazepine (used to prevent epileptic seizures, relieve certain types of pain, or control mood disorders) should be avoided during chemotherapy.
• Anticoagulants (medicines used to prevent blood clots) – your doctor will decide whether you should receive these medicines and will perform tests to monitor your blood's clotting tendency.

You must not receive live vaccines while receiving Dacarbazina medac and for 3 months after completing treatment with Dacarbazina medac, because Dacarbazina medac can weaken the immune system and increase the risk of developing a serious infection.
You may receive a "killed" or inactivated vaccine while taking Dacarbazina medac.

Dacarbazina medac with food, drinks and alcohol
During chemotherapy, you must not consume alcoholic beverages.

Pregnancy, breastfeeding and fertility
Dacarbazina medac must not be administered if you are pregnant, suspect you may be pregnant, or are planning a pregnancy.
Do not breastfeed during treatment with Dacarbazina medac.
You must use effective contraception during treatment with Dacarbazina medac. Men must continue to use effective contraception for at least 6 months after stopping treatment with Dacarbazina medac.
If you intend to become pregnant or to breastfeed, consult your doctor first.

Driving and using machines
This medicine may affect your ability to drive vehicles or operate machinery due to effects on the central nervous system (effects on the brain and nerves) or due to nausea and vomiting. However, between treatment cycles, you may drive or use machinery unless you experience dizziness or feel unsteady.

3. How to use Dacarbazina medac

This medicine will be administered to you under the supervision of an oncologist (a specialist in cancer treatment) or a hematologist (a specialist in blood diseases). You will be regularly monitored during and after treatment to detect any signs of adverse effects.
Dacarbazine is a photosensitive substance. The doctor or nurse administering this medicine will ensure that you are protected from exposure to daylight during administration.

Dacarbazina medac dosage
Your doctor will calculate the dose to be administered to you. This will depend on the type and stage of cancer, your body surface area (m²), blood cell counts, and any other anticancer medicines or therapies you are receiving. Your treating doctor will also individually determine the duration of treatment with this medicine.
Your doctor may adjust the dose and frequency of administration based on blood test results, your general health condition, additional therapies, and your response to this medicine. If you have any doubts about your treatment, consult your doctor, nurse, or pharmacist.

Skin cancer (metastatic malignant melanoma)
The usual dose is 200 – 250 mg per m² of body surface area, once daily. You will receive this dose for 5 consecutive days every 3 weeks. The dose will be administered either as a rapid intravenous injection or as a slow intravenous infusion lasting 15 – 30 minutes.
Alternatively, you may receive a higher dose (850 mg per m² of body surface area) every 3 weeks, administered as a slow intravenous infusion.

Lymphatic tissue cancer (Hodgkin's disease)
The usual dose is 375 mg per m² of body surface area, every 15 days. You will also receive medicines called doxorubicin, bleomycin, and vinblastine (this combination is known as the ABVD regimen), administered as slow intravenous infusions.

Cancer of muscle, fat, fibrous, blood vessel, and other supportive tissues of the body (soft tissue sarcoma)
The usual dose is 250 mg per m² of body surface area, once daily. You will receive this dose for 5 consecutive days every 3 weeks, administered as a slow intravenous infusion lasting 15 – 30 minutes.
You will also be administered a medicine called doxorubicin (this combination is known as the ADIC regimen).

Patients with kidney or liver problems
If you have mild or moderate kidney or liver problems, dose reduction of this medicine is usually not necessary. If you have problems affecting both the kidney and liver, your body will take longer to process and eliminate the medicine. Your doctor may prescribe a reduced dose of this medicine.

Use in children
Specific recommendations for the use of this medicine in children cannot be provided until further data become available.

If you have been administered more Dacarbazina medac than you should have
Administration of an excessive amount of Dacarbazina medac may cause a severe reduction in blood cell counts. This could lead to complete loss of bone marrow function. Possible symptoms include signs of infection, bruising due to increased bleeding tendency, or fatigue, and these may appear up to 2 weeks later.
If you think you have been administered too much Dacarbazina medac, inform your doctor or nurse immediately.
Your blood cell counts will be monitored, and supportive measures such as blood transfusions may be necessary.

If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Your doctor will explain these to you, outlining the risks and benefits of the treatment.
Immediately inform your doctor if you notice any of the following:

• signs of infection such as sore throat and high fever
• unusual bruising or bleeding
• extreme tiredness
• persistent or severe vomiting or diarrhoea
• severe allergic reaction; you may develop a sudden skin rash with itching, swelling of hands, feet, ankles, face, lips, mouth or throat (possibly causing difficulty in swallowing or breathing), and feel faint
• yellowing of the skin and eyes due to liver problems
• signs of brain or nerve problems such as headache, vision impairment, seizures, confusion, lethargy, or numbness and tingling of the face
• Severe liver disease due to blockage of blood vessels in the liver (veno-occlusive disease [VOD] or Budd-Chiari syndrome), with destruction of liver cells (hepatic necrosis), which may be fatal. If such complications are suspected, your doctor will decide the appropriate treatment for you. All of these are serious side effects that may require immediate medical attention.

Other side effects listed below may also occur:

Common (may affect up to 1 in 10 people)

• Decrease in red blood cell count (anaemia)
• Decrease in white blood cell count (leucopenia)
• Decrease in platelet count (thrombocytopenia). Blood count changes are dose-dependent and delayed; the lowest values are often observed only after 3–4 weeks.
• Loss of appetite (anorexia), nausea and vomiting (all of which may be severe)

Uncommon (may affect up to 1 in 100 people)

• Hair loss (alopecia)
• Increased skin pigmentation (hyperpigmentation)
• Skin sensitivity to light (photosensitivity)
• Flu-like symptoms such as fatigue, chills, fever and muscle pain. These symptoms may occur during administration of the medicine or a few days afterwards. They may also recur upon subsequent administration of dacarbazine.
• Infections

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

• Decrease in all blood cell counts (pancytopenia)
• Severe reduction in granulocytes, a specific type of white blood cell (agranulocytosis)
• Severe allergic (anaphylactic) reaction, manifesting for example as a drop in blood pressure, swelling of hands, feet, ankles, face, lips, mouth and throat, possibly causing difficulty in swallowing or breathing, rapid pulse, hives and widespread itching or skin redness
• Headache
• Impaired vision
• Confusion
• Lethargy
• Epileptic seizures (convulsions)
• Altered facial sensation (facial paraesthesia), numbness and redness of the face shortly after injection
• Diarrhoea
• Increased liver enzymes
• Impaired kidney function
• Skin redness (erythema)
• Skin rashes (maculopapular exanthema)
• Urticaria
• Irritation at the site of administration

If this medicine is accidentally injected into the tissue surrounding a vein, pain and tissue damage may occur.
One or more of these symptoms may occur. If you experience any side effect,
including those not listed in this leaflet, consult your doctor or pharmacist.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist.
You may also report side effects directly via the website
http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Dacarbazina medac

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 the carton after "Exp.". The expiry date refers to the last day of that month.
Do not store above 25°C. Keep the vial in the outer packaging to protect the medicine from light.
The shelf life of the medicine under these conditions is 3 years.
Even freshly prepared (reconstituted) and further diluted solutions of Dacarbazina medac must be protected from light and used immediately.
Dacarbazina medac is for single use only.
The physician must discard any remaining contents after use and any solutions showing visible changes in appearance. After dilution, the infusion solution must be visually inspected by the physician, and only clear solutions, free from particulate matter, should be used.

6. Package contents and other information

What Dacarbazina medac contains

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

Description of the appearance of Dacarbazina medac and contents of the pack
Dacarbazina medac is a white or pale yellow powder contained in amber glass vials (type I, European Pharmacopoeia).
Each single-dose vial of Dacarbazina medac 500 mg contains 500 mg of dacarbazine (dacarbazine citrate).
After reconstitution and final dilution, Dacarbazina medac 500 mg contains 1.4 – 2.0 mg/mL of dacarbazine.
Each single-dose vial of Dacarbazina medac 1000 mg contains 1000 mg of dacarbazine (dacarbazine citrate).
After reconstitution and final dilution, Dacarbazina medac 1000 mg contains 2.8 – 4.0 mg/mL of dacarbazine.
The vials of Dacarbazina medac are packed in boxes containing 1 vial each.

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

This medicinal product is authorized in the European Economic Area countries under the following names:
Austria Dacarbazine medac 500 mg/1000 mg, powder for solution for infusion
Belgium DACARBAZINE MEDAC 500 mg/1000 mg, powder for solution for infusion
DACARBAZINE MEDAC, powder for solution for perfusion
DACARBAZINE MEDAC, powder for solution for infusion
Denmark Dacarbazine medac 500 mg/1000 mg, powder for infusion solution
Germany Detimedac 500 mg/1000 mg, powder for solution for infusion
Ireland Dacarbazine medac 500 mg/1000 mg, powder for solution for infusion
Italy Dacarbazina medac 500 mg/1000 mg, powder for solution for infusion
Netherlands Dacarbazine medac 500 mg/1000 mg, powder for solution for infusion
Portugal Dacarbazina medac 500 mg/1000 mg, powder for solution for perfusion
Spain Dacarbazina medac 500 mg/1000 mg, powder for solution for perfusion
Sweden Dacarbazine medac 500 mg/1000 mg, powder for infusion solution
United Kingdom Dacarbazine medac 500 mg/1000 mg, powder for solution for infusion

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The following information is intended exclusively for physicians or healthcare professionals:
Recommendations for safe handling
Dacarbazine is an antineoplastic agent and must be handled according to standard procedures for cytotoxic drugs with mutagenic, carcinogenic, and teratogenic effects. Before proceeding, consult local guidelines regarding cytotoxic agents.
Dacarbazine should only be opened by trained personnel, and precautions must be taken to avoid exposure, as with all cytotoxic agents. Handling cytotoxic drugs should generally be avoided during pregnancy. The solution for administration must be prepared in a designated area, working on a washable tray or on absorbent paper with a plastic backing, wearing appropriate eye protection, disposable gloves and gown, and a face mask. Syringes and infusion sets must be assembled carefully to prevent leakage (use of Luer lock adapters is recommended).
After preparation, any exposed surfaces must be thoroughly cleaned, and hands and face must be washed.
In case of spillage, personnel must wear gloves, face mask, eye protection, and disposable gown, and collect the spilled material using absorbent material specifically intended for this purpose, applied to the affected area. The area must then be cleaned, transferring all contaminated material into a bag or container for cytotoxic waste, or sealing it for incineration.

Preparation for intravenous administration
Dacarbazine solutions must be prepared immediately before use.
Dacarbazine is light-sensitive. During administration, the infusion container and administration set must be protected from daylight, e.g., by using light-resistant PVC infusion sets. Standard infusion sets should be wrapped, e.g., in UV-resistant film.

a) Preparation of Dacarbazina medac 500 mg:
Under aseptic conditions, transfer 50 mL of Water for Injections into the vial and shake until a solution is obtained. The resulting solution, containing 10 mg/mL of dacarbazine (solution density: ρ = 1.007 g/mL), must be further diluted with 200 – 300 mL of 0.9% sodium chloride or 5% glucose infusion solution. This infusion solution, containing 1.4 – 2.0 mg/mL of dacarbazine, is ready for intravenous administration and must be administered within 20 – 30 minutes.

b) Preparation of Dacarbazina medac 1000 mg:
Under aseptic conditions, transfer 50 mL of Water for Injections into the vial and shake until a solution is obtained. The resulting solution, containing 20 mg/mL of dacarbazine (solution density: ρ = 1.015 g/mL), must be further diluted with 200 – 300 mL of 0.9% sodium chloride or 5% glucose infusion solution. This infusion solution, containing 2.8 – 4.0 mg/mL of dacarbazine, is ready for intravenous administration and must be administered within 20 – 30 minutes.

Dacarbazina medac 500 mg (1000 mg) is for single use only.
After dilution, the infusion solution must be inspected visually; only clear solutions free from particulate matter should be used. Do not use the solution if particulate matter is present.
Discard any remaining contents after use and solutions showing any change in visual appearance.
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations.