DACARBAZINE MEDAC

Posology The use of dacarbazine should be confined to physicians experienced in oncology or haematology. The following regimes may be used. For further details see current scientific literature. v. injection for 5 days every 3 weeks. As an alternative to an intravenous bolus injection dacarbazine can be administered as a short- term infusion (over 15 – 30 minutes).

It is also possible to give 850 mg/m² body surface area on day 1 and then once every 3 weeks as intravenous infusion. v. every 15 days in combination with doxorubicin, bleomycin and vinblastine (ABVD regimen). v. (days 1 - 5) in combination with doxorubicin every 3 weeks (ADIC regimen).

During dacarbazine treatment frequent monitoring of blood counts should be conducted as well as monitoring of hepatic and renal function. Since severe gastrointestinal reactions frequently occur, antiemetic and supportive measures are advisable.

Because severe gastrointestinal and haematological disturbances can occur an extremely careful benefit-risk analysis has to be made before every course of therapy with dacarbazine. Duration of therapy The treating physician should individually decide about the duration of therapy taking into account the type and stage of the underlying disease, the combination therapy administered and the response to and adverse effects of dacarbazine.

In advanced Hodgkin’s disease, a usual recommendation is to administer 6 cycles of ABVD combination therapy. In metastasised malignant melanoma and in advanced tissue sarcoma, the duration of treatment depends on the efficacy and tolerability in the individual patient.

Renal and/or hepatic impairment If there is mild to moderate renal or hepatic insufficiency alone, a dose reduction is not usually required. In patients with combined renal and hepatic impairment elimination of dacarbazine is prolonged.

However, no validated recommendations on dose reductions can be given currently. Elderly As limited experience in elderly patients is available no special instructions for the use in elderly patients can be given. Paediatric population The safety and efficacy of dacarbazine in children/adolescents aged < 15 years have not yet been established.

No special recommendations for the use of dacarbazine in the paediatric age group can be given until further data become available. Method of administration Precautions to be taken before handling or administering the medicinal product Dacarbazine is sensitive to light exposure.

Frequencies Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1000 to < 1/100) Rare (≥ 1/10000 to < 1/1000) Very rare (< 1/10000) Not known (cannot be estimated from the available data) The most commonly reported ADRs are gastrointestinal disorders (anorexia, nausea and vomiting) and blood and lymphatic system disorders such as anaemia, leukopenia and thrombocytopenia.

The latter are dose-dependent and delayed, with the nadirs often only occurring after 3 to 4 weeks. g. alkaline phosphatase, ASAT, ALAT), blood lactate dehydrogenase (LDH) increased, blood creatinine increased, blood urea increased Description of selected adverse reactions Changes in blood counts often observed (anaemia, leukopenia, thrombocytopenia) are dose- dependent and delayed, with the nadirs often only occurring after 3 to 4 weeks..

Flu-like symptoms with exhaustion, chills, fever and muscular pain are occasionally observed during or often only days after dacarbazine administration. These disturbances may recur with the next infusion. Rarely liver necrosis due to occlusion of intrahepatic veins (veno-occlusive disease of the liver) has been observed after administration of dacarbazine in monotherapy or in combined treatment modalities.

In general the syndrome occurred during the second cycle of therapy. Symptoms included fever, eosinophilia, abdominal pain, enlarged liver, jaundice and shock which worsened rapidly over a few hours or days. 4). Application site irritations and some of the systemic adverse reactions are thought to result from formation of photodegradation products.

Facial paraesthesia and flushing may occur shortly after injection. Allergic reactions of the skin in the form of erythema, maculopapular exanthema or urticaria are observed rarely. Inadvertent paravenous injection is expected to cause local pain and necrosis.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

It is recommended that dacarbazine should only be administered under the supervision of a physician specialised in oncology who has the facilities for regular monitoring of clinical, biochemical and haematological effects, during and after therapy.

If symptoms of a liver or kidney functional disorder or symptoms of a hypersensitivity reaction are observed immediate cessation of therapy is required. If veno-occlusive disease of the liver occurs, further therapy with dacarbazine is contraindicated.

Note:

The responsible physician should be aware of a rarely observed severe complication during therapy resulting from liver necrosis due to occlusion of intrahepatic veins. Therefore frequent monitoring of liver size, function and blood counts (especially eosinophils) is required.

8). Long-term therapy can cause cumulative bone marrow toxicity. The possible bone marrow depression requires careful monitoring of white blood cells, red blood cells and platelet levels. Haemopoietic toxicity may warrant temporary suspension or cessation of therapy.

v. administration may result in tissue damage and severe pain. 5). Dacarbazine is a moderate immunosuppressive agent. Administration of live vaccines to patients who are immunocompromised as a result of treatment with chemotherapeutics such as dacarbazine can cause serious and potentially fatal infections.

Immunisation with live vaccines should therefore be avoided during dacarbazine therapy. It is generally advised to use live virus vaccines with caution after stopping chemotherapy and to take the patient’s immune status into account, depending also on the disease and other therapies.

Vaccination with live vaccines should be administrated no sooner than 3 months after the completion of chemotherapy. Inactivated vaccines can be used if available. 5). Hepatotoxic medicinal products and alcohol should be avoided during chemotherapy.

6), • leukopenia and/or thrombocytopenia, • severe liver or kidney diseases.