Duticin

Each 20 mL vial contains Dacarbazine, BP 200 mg.

Pharmacology: Pharmacodynamics: Dacarbazine is a cytostatic agent. The antineoplastic effect is due to an inhibition of cell growth which is independent of the cell cycle and due to an inhibition of DNA synthesis. An alkylating effect has also been shown and other cytostatic mechanisms may also be influenced by dacarbazine.
Dacarbazine is considered not to show an antineoplastic effect by itself. However by microsomal N-demethylation it is quickly converted to 5-amino-imidazole-4-carboxamide and a methyl cation, which is responsible for the alkylating effect of the drug.
Pharmacokinetics: After intravenous administration dacarbazine is quickly distributed into tissue. Plasma protein binding is 5%. Kinetics in plasma are biphasic; the initial (distribution) half life is only 20 minutes, terminal half life is 0.5-3.5 hours.
Dacarbazine is inactive until metabolised in the liver by cytochromes P450 to form the reactive N-demethylated species HMMTIC and MTIC. This is catalysed by CYP1A1, CYP1A2, and CYP2E1. MTIC is further metabolised to 5-aminoimidazole-4-carboxamide (AIC).
Dacarbazine is metabolized mainly in the liver by both hydroxylation and demethylation, approx. 20-50% of the drug is excreted unmodified by the kidney via renal tubular secretion.

Metastatic malignant melanoma, Hodgkin's disease, neuroblastoma, soft-tissue sarcoma including leiomyosarcoma.

It is given intravenously in doses of 2 to 4.5 mg per kg body-weight daily for 10 days, repeated at intervals of 4 weeks, or 250 mg per m² body-surface daily for 5 days, repeated at intervals of 3 weeks.
Malignant Melanoma: It can also be given in a dose of 850 mg per m² by intravenous infusion at 3-week intervals.
Hodgkin's Disease: The recommended dosage of Dacarbazine in the treatment of Hodgkin's disease is 150 mg/m²/day for 5 days, in combination with other effective drugs.
Treatment may be repeated every 4 weeks. An alternative recommended dosage is 375 mg/m²/day, in combination with other antineoplastic agents, to be repeated every 15 days.
Dosage of dacarbazine must be based on the clinical and hematologic response and tolerance of the patient in order to obtain optimum therapeutic results. Inject over 1 to 2 minutes.
Reconstitution: Reconstitute with Sterile Water for Injection. 200 mg: 20 mL.
After reconstitution, the solution should be used immediately. Reconstituted solution is stable for up to 8 hours at normal room temperatures and light or up to 72 hours at 4°C.
Precautions on Administration: Since mixing with other drugs may cause crystal formation or apparent change, the mixture injection should be avoided.
Subcutaneous or intramuscular injection should be avoided.
Since intravenous injection may cause vessel pain, injection site and injection method should be cautioned, and also the injection should be done slowly.
Extravasations of dacarbazine must be avoided as it may cause induration, sphacelism at the injection site.

The primary anticipated complications of overdose are severe bone marrow suppression, eventually bone marrow aplasia which may be delayed by up to two weeks.
Time to occurrence of nadirs of leucocytes and thrombocytes can be 4 weeks. Even if overdosage is only suspected, long-term careful haematological monitoring is essential and supportive measures, e.g. appropriate transfusions for bone marrow suppression may be required. There is no known antidote for dacarbazine overdose. Therefore, special care has to be taken to avoid overdose of this drug.

Patients who have demonstrated a hypersensitivity to it in the past.
Pregnant women or women who are suspected of being pregnant.

Patients with hepatic impairment.
Patients with renal impairment.
Patients with infection as a complication.
Patients with chickenpox (Fetal systemic impairment may occur).
Severe side-effects such as bone marrow depression, hepatic impairment, renal impairment may occur; therefore, careful monitoring (blood-hepatic-renal function) is needed. If any symptom occurs, the administration should be discontinued or appropriate therapy instituted.
In long-term therapy, side-effects may be chronic or more severe. Therefore, careful treatment is needed.
Bleeding tendency should be cautioned.
With the effect on gonads, use in patients of child bearing age should be considered.
Others: In the long-term therapy patients, acute leukemia has been reported. Studies have demonstrated that tumor is developed when administered to animals (mice, rats) orally. Studies have been reported that spermatogenic depression is recognized. In studies using lymphocytoma of mice, mutagenicity has been recognized.
Use in children: Safe use in children has not been established.
Use in pregnancy & lactation: Studies have demonstrated that this agent is teratogenic when administered to animals. Dacarbazine therefore should not be administered to pregnant women or women who are suspected of being pregnant.
Since the safe use in nursing mothers has not been established, breast feeding should be avoided during dacarbazine therapy.

Studies have demonstrated that this agent is teratogenic when administered to animals. Dacarbazine therefore should not be administered to pregnant women or women who are suspected of being pregnant.
Since the safe use in nursing mothers has not been established, breast feeding should be avoided during dacarbazine therapy.

Hematologic: Pancytopenia, anemia, leukopenia, and thrombocytopenia may occur; therefore, careful monitoring is needed. If any symptom occurs, the administration should be discontinued or appropriate therapy instituted.
Hepatic: Increase of GOT-AL-P-LDH-total bilirubin level, decrease of serum total protein may occur. Hepatic impairment accompanied by venae hepaticae thrombosis and hepatocyte sphacelism has been reported; if they occur, the administration should be discontinued or appropriate therapy instituted.
Renal: Increase of BUN, proteinuria may occur.
Hypersensitivity: Anaphylaxis, photosensitivity may occur.
Gastrointestinal: Nausea, vomiting, anorexia, diarrhea, and gastralgia may occur.
Nervous System: Giddiness, mouth numbness, facial paresthesia may occur.
Dermatologic: Erythematous eruption, urticaria, alopecia may occur.
Site of Injection: Vascular pain may occur.
Other: Malaise, myalgia, headache, ruber, flush, influenza-like syndrome may occur.

Concomitant therapy with other anti-neoplastic drugs or radiotherapeutics may increase side effects including bone marrow depression.

Store at temperatures between 2°C-8°C. Protect from light.

Cytotoxic Chemotherapy

L01AX04 - dacarbazine ; Belongs to the class of other alkylating agents. Used in the treatment of cancer.

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