DACARBAZINE 100 MG POWDER FOR SOLUTION FOR INJECTION OR INFUSION

Package leaflet: Information for the user

Powder for solution for injection or infusion Dacarbazine Read all of this leaflet carefully before you start having this medicine. Keep this leaflet. You may need to read it again. f you have any further questions, ask your doctor, nurse I or pharmacist. his medicine has been prescribed for you. Do not pass T it on to others. It may harm them, even if their symptoms are the same as yours. f any of the side effects gets serious, or if you notice any I side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist. In this leaflet: 1. What Dacarbazine is and what it is used for 2. Before you have Dacarbazine 3. How you have Dacarbazine 4. Possible side effects 5. How to store Dacarbazine 6. Further information

l100 mg

Tests: During your treatment the following things will be checked: iver size and how well your liver is working (through L blood tests). This is to check that the veins in your liver are not being blocked. If your liver is affected, treatment will be stopped. mount of red, white and platelet blood cells in your blood A (through blood tests). This is to check that your bone marrow is working properly to help create blood cells. If your bone marrow is affected, treatment may be stopped for a while or stopped completely. Men who are being treated with dacarbazine are advised to take contraceptive measures during therapy and for 6 months after the end of therapy. Using other medicines Please tell your doctor or nurse if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription, including herbal medicines. This is because Dacarbazine can affect the way some other medicines work. Also some other medicines can affect the way Dacarbazine works. In particular, do not have this medicine and tell your doctor, nurse or pharmacist if you are using any of the following: Phenytoin for fits (seizures) Other medicines which might damage your liver. Do not use Dacarbazine if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before having Dacarbazine. Tell your doctor, nurse or pharmacist if you are using any of the following: adiation treatment or other medicines to reduce tumour R growth (chemotherapy). Using these medicines with Dacarbazine can increase the damage to your bone marrow. ther medicines that are metabolized by a system of liver O enzymes called cytochrome P450. ethoxypsoralen for skin problems such as psoriasis and M eczema. Having Dacarbazine with Methoxypsoralen can make you more sensitive to sunlight (photosensitisation). otemustine You should not use dacarbazine earlier F than one week after fotemustine administration to avoid damage to your lungs. yclosporin or tacrolimus: these medicines may reduce C the function of your immune system. If any of the above apply to you (or you are not sure), please tell your doctor, nurse or pharmacist before having Dacarbazine. Your doctor will decide whether use of medicines to improve the blood flow should be given to you and will check your clotting tendency of the blood. Using vaccines There is different advice for different types of vaccines: ellow-fever You must not have a yellow-fever vaccine if Y you are having Dacarbazine. ive vaccines You should not have a live vaccine if you L are having Dacarbazine. This is because Dacarbazine may weaken your immune system and make you more likely to catch a serious infection. illed vaccines You may have a killed or inactivated K vaccine if you are having Dacarbazine. Having Dacarbazine with food and drink o not eat just before having Dacarbazine. This could D make you feel less sick or be less sick. Do not drink alcohol during your treatment. Pregnancy and breast-feeding o not have Dacarbazine if you are pregnant or planning D to become pregnant. This is because the medicine can damage your unborn child. uring treatment men and women need to use a reliable D method of contraception. If you become pregnant, tell your doctor straight away. en who are being treated with Dacarbazine also need to M use a reliable method of contraception for 6 months after the end of therapy. o not breast-feed during your treatment with D Dacarbazine.

Driving and using machines You may feel sleepy, confused or having impaired vision while having Dacarbazine. You may also feel or be sick. If any of these happen, do not drive or use any tools or machines.

3.HOW YOU HAVE DACARBAZINE
Your doctor will decide how long your treatment should last. This will depend upon: The type of cancer you have and how advanced it is hich treatment you are being given and how well you W are responding to it Whether you are having any side effects How much you will be given The amount you are given is worked out depending on your size (m2 body surface area).

1. HAT DACARBAZINE IS AND WHAT IT IS W USED FOR
What Dacarbazine is Dacarbazine belongs to a group of medicines called cytotoxic drugs, often called chemotherapy. Treatment with Dacarbazine should only be carried out by doctors who specialise in the treatment of cancer (oncologists) or blood problems (haematologists). What Dacarbazine is used for Dacarbazine is used to treat a type of skin cancer called metastatic malignant melanoma. This is a type of skin cancer which has spread to another part of your body. Dacarbazine is also used together with other medicines for: dvanced cancer of a part of your immune system called A the lymphatic system. This type of cancer is often called Hodgkins disease. dvanced soft tissue sarcoma in adults (exceptions: A mesothelioma, Kaposi sarcoma). Soft tissue sarcomas are malignant tumours which arise from the soft tissues of the body. Tumours may be found in many places such as around your nerves, muscles or blood vessels. How Dacarbazine works Dacarbazine helps to stop your cancer cells growing and multiplying.

Skin cancer that has spread (metastatic malignant melanoma) he usual dose is 200250 mg per m2 body surface T area, once a day. ou are given this 5 days in a row, every 3 weeks. You Y then have a break. t will be given as a fast injection into your vein or as I a slow infusion into your vein lasting 15 to 30 minutes. lternatively, you can be given one larger dose of 850 A mg per m2 body surface area, every 3 weeks. This will be given as a slow infusion into your vein. Cancer of your lymphatic system (Hodgkins disease) he usual dose is 375 mg per m2 body surface area, T every 15 days. ou will also be given medicines called doxorubicin, Y bleomycin and vinblastin (this combination is called the ABVD regimen). ou will usually do this 6 times. Y t will be given as a slow infusion into the vein. I Cancer of the tissues that join your body togeher (soft tissue sarcoma) he usual dose is 250 mg per m2 body surface area, once T a day. ou will also be given a medicine called doxorubicin (this Y combination is called the ADIC regimen). ou are given this 5 days in a row, every 3 weeks. You Y then have a break. t will be given as a slow infusion into the vein lasting I 1530 minutes. Patients with kidney or liver problems If you have either mild or moderate kidney or liver problems, you do not usually need to have less of this medicine. If you have both kidney and liver problems, your body will take longer to use the medicine and remove it from your system. Your doctor may give you less of this medicine. Elderly people There are no special instructions for the use of Dacarbazine in elderly people. Children Until further data become available, no special recommendations for the use of Dacarbazine in children can be given.
If you have more Dacarbazine than you should If you think that you have been given too much Dacarbazine, tell your doctor or nurse straight away. f an overdose is suspected, the numbers of your blood I cells will be checked and supportive meaures such as transfusions may be required. n overdose would cause severe damage to your bone A marrow (bone marrow toxicity). This can lead to a complete loss of function of your bone marrow (bone marrow aplasia). This can be delayed by up to 2 weeks. If you have any further questions on the use of this product, ask your doctor, nurse or pharmacist.

2.BEFORE YOU HAVE DACARBAZINE
Do not have Dacarbazine if: ou are allergic (hypersensitive) to dacarbazine or any of Y the other ingredients of this medicine (listed in Section 6) ou are pregnant or are breastfeeding your child Y ou have a low number of white blood cells (leukopenia) Y or a low number of platelets (thrombocytopenia) You have severe liver or kidney problems In combination with yellow fever vaccine Do not have Dacarbazine if any of the above apply to you. If you are not sure, talk to your doctor, nurse or pharmacist before using Dacarbazine. Take special care with Dacarbazine Your doctor will need to ensure appropriate administration of dacarbazine in order to prevent tissue damage and pain. Extravasation (injection of the solution into the tissue around the vein) can lead to tissue damage and severe pain.

4.POSSIBLE SIDE EFFECTS
Like all medicines, Dacarbazine can cause side effects, although not everybody gets them. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist. Common (affects 1 to 10 users in 100) oss of appetite (anorexia), feeling sick or being sick. L If anyone helps to clean up your sick, they must wear gloves. This is because some of the medicine may pass into their skin. lood problems. These are dependent on how strong B your dose is and are most likely after 3 to 4 weeks. You may feel tired, look pale, bruise more easily than usual or get more infections than usual. They are shown by blood tests: anaemia (decreased red blood cells) leukopenia (decreased white blood cells) thrombocytopenia (decreased platelets) one marrow suppression (decreased formation of all b blood cells in the bone marrow) Uncommon (affects 1 to 10 users in 1,000) lu-like symptoms such as tiredness, chills, fever or F muscle pain. These are more likely in the first few days of each treatment cycle bnormal kidney function or increased liver enzymes A (shown in tests) iver damage (hepatotoxicity) L lockage of a vein in your liver (also called Budd-chiari B syndrome) iver tissue damage (necrosis) due to blockage of a L vein in your liver. The signs include fever, stomach pain, yellow eyes and skin (jaundice). Your doctor would also be able to see that your liver was larger and you would have changes in the numbers of your blood cells. This is most likely in your second cycle. ark patches on your skin (hyperpigmentation) D ncreased sensitivity of your skin to sunlight I (photosensitivity) air loss (alopecia) H eeling confused F lushed face F ransient rash T lurred vision B Rare (affects 1 to 10 users in 10,000) njection site reactions such as vein irritation I ed skin (erythema), a rash with spots and blisters R (maculopapular exanthema) or a nettle rash (urticaria) kin reactions where the medicine is injected S welling of the face, lips, mouth and throat with difficulty S breathing (anaphylactic reaction) eeling sleepy, having impaired vision F eadache H its (seizures) F ins and needles sensation in the face P iarrhoea. If anyone helps to clean up your diarrhoea, D they must wear gloves. This is because some of the medicine may pass into their skin. lood problems. These are dependent on how strong your B dose is and are most likely after 3 to 4 weeks. You may feel tired, look pale, bruise more easily than usual or get more infections than usual. They are shown by blood tests pancytopenia (all blood cells decreased) granulocytosis (marked decrease in one type of white a blood cell called a granulocyte) If the medicine is accidentally injected into the tissue around your vein, it will be painful and there will be tissue damage. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.

Do not have Dacarbazine if the solution is cloudy or has bits floating in it. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment. Do not store above 25 C. Store in the original package in order to protect from light.

The solution must be administered carefully to avoid extravasation (injection of the solution into the tissue around the vein), as this can cause local pain and tissue damage. If extravasation occurs the injection must be immediately interrupted and the remaining dose administered in a different vein.

Shelf life of the reconstituted solution Chemical and physical in-use stability has been demonstrated for 1 hour at 25 C and for 24 hours at 4 C and protected from light. Shelf life of diluted solution for infusion Chemical and physical in-use stability has been demonstrated for 30 minutes at 25 C and for 8 hours at 4C and protected from light.

6.FURTHER INFORMATION
What Dacarbazine contains he active substance is dacarbazine (100 mg per vial). T he other ingredients are citric acid monohydrate and T mannitol (E 421). What Dacarbazine looks like and contents of the pack Dacarbazine is a white powder that is made up into a clear liquid for injection or infusion. It is packed in cartons each containing 10 vials. Not all pack sizes may be marketed. Marketing Authorisation Holder and Manufacturer Lipomed GmbH Hegenheimer Strasse 2 D 79576 Weil / Rhein Germany Telephone number: +49-7621-1693 472 Fax number: +49-7621-1693 474 E-Mail: lipomed@lipomed.com This medicinal product is authorised in the Member States of the EEA under the following names: Austria: Dacarbazin Lipomed 100 mg Pulver zur Herstellung einer Injektions- oder Infusionslsung Germany: Dacarbazin Lipomed 100 mg Pulver zur Herstellung einer Injektions- bzw. Infusionslsung Spain: Dacarbazina Lipomed 100 mg polvo para solucin inyectable o para solucin para perfusin France: Dacarbazine Lipomed 100 mg poudre pour solution pour injection ou pour perfusion Italy: Dacarbazina Lipomed 100 mg polvere per soluzione iniettabile o per soluzione per infusione United Kingdom: Dacarbazine 100 mg powder for solution for injection or infusion This leaflet was last approved in 01/2010. The following information is intended only for doctors and/ or medical personnel It is recommended that the patency of the vein is tested with 5 to 10 ml of isotonic sodium chloride solution or glucose 5%. The same solution will be used to rinse the remaining medicine out of the infusion tube.

Notes on safe handling Dacarbazine is an antineoplastic agent (it reduces the growth of cancer cells). Before preparing a solution, local cytotoxic (cell damaging) guidelines should be referred to regarding handling of cytotoxic agents. Dacarbazine should only be opened by trained staff. As with all cytotoxic agents, precautions should be taken to avoid exposing staff. Handling of cytotoxic drugs should be generally avoided during pregnancy. Preparation of the solution for administration should be carried out in a designated handling area and working over a washable tray or disposable plastic-backed absorbent paper. It is recommended that suitable eye protection, disposable gloves, face mask and a disposable apron are worn. Syringes and infusion sets should be assembled carefully to avoid leaks (use of Luer lock fittings is recommended). Once completed, any exposed surface should be thoroughly cleaned and the hands and face washed. In the event of spillage, operators should put on gloves, face masks, eye-protection and a disposable apron and mop up the spilled material with an absorbent material laid out in the area for that purpose. The area should then be cleaned and all contaminated material transferred to a cytotoxic spillage bag or bin or sealed for incineration. Preparation of the solution for intravenous dosing (administration into a vein) Dacarbazine solutions should be prepared immediately before use. Dacarbazine is sensitive to light. During the treatment the infusion container and infusion set has to be protected from light, for example by using a light-resistant PVC infusion set. Other infusion sets should, for example, be wrapped in light resistant aluminium foil. Preparation and administration of the solution for injection/ infusion Dacarbazine 100 mg powder for solution for injection or infusion will be reconstituted with 9.9 ml of water for injections, that means the powder will be completely dissolved. The resulting solution contains 10 mg/ml dacarbazine. The solution will be given as a slow injection it will be injected slowly into a vein. At higher doses, the reconstituted solution will be diluted with 200 ml glucose 5% or sodium chloride solution 0.9% and infused intravenously over 15 to 30 minutes (given slowly into a vein).
Dacarbazine is for single use only. Dacarbazine solution is chemically incompatible with the medicinal products heparin, hydrocortisone, L-cysteine and sodium hydrogen carbonate; this means that dacarbazine solution should not be mixed with medicines that contain these substances. This medicinal product must not be mixed with other medicinal products except those mentioned above.

Keep out of the reach and sight of children. Do not have Dacarbazine after the expiry date which is stated on the carton and bottle after EXP. The expiry date refers to the last day of that month.

Dacarbazine is sensitive to light. Reconstituted solutions must therefore be protected from light, including during the infusion (light-resistant infusion set).

DAC-553.L.100.010.UK10

5.HOW TO STORE DACARBAZINE

Administration of the injection/infusion After reconstitution (preparation of the solution) with water for injection and without further dilution with isotonic sodium chloride solution or glucose 5%, Dacarbazin preparations are hypo-osmolar (ca. 100 mOsmol/kg) which means that the solutions contain a lower concentration of dissolved substances than blood; it should therefore be given by slow intravenous injection, e.g., over 1 minute and not as an i.v. bolus injection (fast injection) over a few seconds.

Shelf life of the reconstituted solution Chemical and physical in-use stability has been demonstrated for 1 hour at 25 C and for 24 hours at 4 C and protected from light. From a microbiological point of view, the reconstituted solution should be used immediately. If the reconstituted solution is not used immediately, the duration and conditions of storage are the responsibility of the user. The reconstituted solution should not be stored for longer than 24 hours in the refrigerator (2 to 8 C) and protected from light, unless reconstitution has taken place in controlled and validated aseptic conditions. Shelf life of diluted solution for infusion Chemical and physical in-use stability has been demonstrated for 30 minutes at 25 C and for 8 hours at 4C and protected from light. From a microbiological point of view, the diluted solution should be used immediately. If the diluted solution for infusion is not used immediately, the duration and conditions of storage are the responsibility of the user. The diluted solution for infusion should not be stored for longer than 8 hours in the refrigerator (2 to 8 C) and protected from light, unless reconstituion has been taken place in controlled and validated aseptic conditions.
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