Medicinal Products

DACARBAZINE MEDAC 500 mg

Generic drug of the therapeutic class: Oncology and Hematology
Active ingredients: Dacarbazine
laboratory: Medac Gmbh

Powder for IV infusion solution
Box of 5 500 mg single dose vials
All forms

Indication

Dacarbazine medac is indicated for the treatment of patients with metastatic malignant melanoma.

Other indications for dacarbazine in the context of a multidrug therapy are:

· Hodgkin's disease.

· Sarcomas of the soft tissues of the adult.

Dosage DACARBAZINE MEDAC 500 mg Powder for solution for infusion IV Box of 5 500 mg single dose vials

The use of Dacarbazine medac should be reserved for experienced physicians in oncology or hematology.

Dacarbazine is sensitive to light. Reconstituted solutions should be protected from light, including during administration (opaque infusion).

Administration of the injection should be done with caution to avoid extravasation into the tissues as this would result in localized pain and tissue damage. In case of extravasation, the injection must be stopped immediately and the rest of the dose must be introduced into another vein.

Food absorption prior to administration of dacarbazine should be avoided to limit the severity of nausea and vomiting. Excreta and vomit should be handled with care.

The following dosages may be used. For more details, see current scientific publications.

Malignant melanoma

Dacarbazine can be used as monotherapy at doses of 200 to 250 mg / m 2 body surface area / day IV injection for 5 days every 3 weeks. Dacarbazine can be administered as a short infusion of 30 minutes to 1 hour.

It is also possible to administer 1000 mg / m 2 of body surface area on day 1 and then once every 3 weeks as an intravenous infusion.

Hodgkin's disease

Dacarbazine should be administered IV at a daily dose of 375 mg / m 2 body surface area every 15 days in combination with doxorubicin, bleomycin and vinblastine (ABVD therapy).

Sarcoma of soft tissues

For adult soft tissue sarcomas, dacarbazine should be administered IV at daily doses of 250 mg / m 2 body surface area (Days 1-5) in combination with doxorubicin every 3 weeks (ADIC treatment) .

During treatment with dacarbazine, blood counts, as well as liver and kidney function, should be monitored frequently. As severe gastrointestinal reactions are common, it is advisable to use anti-emetics and symptomatic management measures.

As severe gastrointestinal and hematologic disturbances are possible, an extremely careful evaluation of the benefit / risk ratio is required before each treatment with Dacarbazine medac.

Duration of treatment

The attending physician will need to decide on the duration of individual treatment for each patient taking into account the type and stage of the underlying disease, the associated chemotherapy used, the response to dacarbazine and its adverse effects.

In the treatment of Hodgkin's disease, it is usually recommended to administer 6 cycles of ABVD combination therapy.

In the treatment of metastatic malignant melanoma and soft tissue sarcoma, the duration of treatment depends on the efficacy and safety observed in each patient.

Rate of administration of the injection / infusion

Doses up to 200 mg / m 2 can be given as a slow intravenous injection of 30 minutes to 1 hour. Higher doses (between 200 and 1000 mg / m 2 ) should be administered as an intravenous infusion over 2 to 3 hours.

It is recommended to first test vein permeability with 5 to 10 ml of isotonic solution for infusion based on sodium chloride or 5% glucose. The same solution should be used after the infusion to purge the drug residues in the tubing.

After reconstitution with water for injections and without further dilution with isotonic sodium chloride or 5% glucose solution, Dacarbazine medac preparations are hypo-osmolar (approximately 100%). mOsmol / kg) and should therefore be administered as a slow intravenous injection of 30 minutes to 1 hour, and not IV bolus injection over a few seconds.

Special populations

Patients with renal / hepatic impairment

In patients with mild to moderate renal or hepatic impairment, it is not usually necessary to reduce the dose. In patients with combined renal and hepatic impairment, elimination of dacarbazine is slower. However, no validated recommendations for dose reduction can currently be provided.

Elderly patients

Since experience in elderly patients is limited, no specific instructions can be provided regarding the use of dacarbazine in this population.

children

No specific recommendations can be made regarding the use of dacarbazine in children until additional data are available.

For preparation and reconstitution instructions, see the Instructions for Use, Handling and Disposal section .

Against indications

Dacarbazine medac is contraindicated in the following cases:

· Hypersensitivity to dacarbazine or any of the excipients.

· Pregnancy or breastfeeding

Leukopenia and / or thrombocytopenia

· Severe hepatic or renal disease.

· In combination with yellow fever vaccine (see section Interactions with other medicinal products and other forms of interaction ).

Medac Dacarbazine side effects

Frequency:

Very common (≥ 1/10)

Frequent (≥ 1/100 to <1/10)

Uncommon (≥ 1/1000 to <1/100)

Rare (≥ 1/10 000 to <1/1000)

Very rare (≥ 1/10 000)

Not known (can not be estimated from the available data)

Blood and lymphatic system disorders

Frequent

Anemia, leukopenia, thrombocytopenia, medullary insufficiency.

Rare

Pancytopenia, agranulocytosis.

Immune system disorders

Rare

Anaphylaxis, hypersensitivity reactions.

Psychiatric disorders

Rare

Confusion.

Nervous system disorders

Rare

Headache, lethargy, convulsions, facial paresthesia.

Eye disorders

Rare

Blurry vision.

Rare

Alteration of vision.

Vascular disorders

Rare

Facial flushing.

Gastrointestinal disorders

Frequent

Anorexia, nausea, vomiting.

Rare

Diarrhea.

Hepatobiliary disorders

Rare

Elevation of transaminases (ASAT, ALT), elevation of alkaline phosphatase, elevation of lactic dehydrogenase (LDH). Hepatotoxicity, hepatic venous thrombosis, hepatic necrosis, potentially fatal Budd-Chiari syndrome.

Skin and subcutaneous tissue disorders

Rare

Alopecia, hyperpigmentation, photosensitivity, transient rash.

Rare

Erythema, maculopapular exanthema, urticaria.

Renal and urinary disorders

Rare

Alteration of renal function with elevation of blood creatinine and blood urea.

General disorders and administration site conditions

Rare

Flu-like symptoms, malaise.

Rare

Irritation at the injection site.

Digestive disorders such as anorexia, nausea and vomiting are common and severe. Rare cases of diarrhea have been observed.

Frequently observed changes in blood counts (anemia, leukopenia, thrombocytopenia) are dose-dependent and delayed, with nadirs often not reached until 3-4 weeks later. Rare cases of pancytopenia and agranulocytosis have been described.

Flu-like symptoms of exhaustion, chills, fever and muscle aches are occasionally observed during or often a few days after administration of dacarbazine. These disorders may reappear during the next infusion.

Elevations of hepatic enzymes (transaminases (ASAT, ALAT), alkaline phosphatase, lactic dehydrogenase (LDH), for example) have been observed infrequently.

Uncommon cases of hepatic necrosis following intrahepatic vein occlusion (veno-occlusive disease) have been observed following dacarbazine monotherapy or multidrug therapy. The syndrome usually occurred during the second treatment cycle. Symptoms included fever, eosinophilia, abdominal pain, increased liver volume, jaundice, and rapidly worsening shock within hours or days. Since fatal changes have been reported, it is particularly important to frequently check liver size, liver function, and blood counts (especially eosinophils) during treatment. In specific cases of suspicion of veno-occlusive disease, rapid treatment with high dose corticosteroids (eg, hydrocortisone 300 mg / day), with or without fibrinolytic agents such as heparin or tissue plasminogen activator, has been shown to be effective (see also sections Posology and method of administration and Warnings and precautions for use ).

Localized disorders at the injection site, such as venous irritations, and some of the systemic adverse reactions may be thought to result from the formation of photodegradation products. Localized pain and necrosis are to be expected in case of accidental extravasation.

Alterations in renal function with elevated blood levels of substances to be excreted in the urine are infrequent.

Central nervous system disorders such as headache, impaired vision, confusion, lethargy and seizures may occur in rare cases. Paresthesia and facial flushing may occur shortly after injection.

Allergic skin reactions such as erythema, maculopapular exanthema or urticaria are observed in rare cases. Alopecia, hyperpigmentation and skin photosensitivity may occur infrequently. Rare cases of anaphylactic reactions have been described.

Reporting of suspected adverse reactions

The reporting of suspected adverse reactions after authorization of the drug is important. It allows continuous monitoring of the benefit / risk ratio of the drug. Health professionals declare any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centers - Website: www.ansm.sante.fr.

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