DESCRIPTION Dacarbazine for injection, USP is a colorless to an ivory colored solid which is light sensitive. Each 20 mL vial contains 200 mg of dacarbazine (active ingredient). Each vial also contains anhydrous citric acid and mannitol. Dacarbazine for injection is reconstituted and administered intravenously (pH 3–4). Dacarbazine for injection is an anticancer agent. Chemically, dacarbazine for injection is 5-(3,3-Dimethyl-1-triazeno) imidazole-4-carboxamide (dacarbazine) with the following structural formula: Chemical Structure Molecular Weight: 182.19 CLINICAL PHARMACOLOGY After intravenous administration of dacarbazine for injection, the volume of distribution exceeds total body water content suggesting localization in some body tissue, probably the liver. Its disappearance from the plasma is biphasic with initial half-life of 19 minutes and a terminal half-life of 5 hours.1 In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours.1 The average cumulative excretion of unchanged dacarbazine in the urine is 40% of the injected dose in 6 hours.1 Dacarbazine is subject to renal tubular secretion rather than glomerular filtration. At therapeutic concentrations dacarbazine is not appreciably bound to human plasma protein. In man, dacarbazine is extensively degraded. Besides unchanged dacarbazine, 5-aminoimidazole -4 carboxamide (AIC) is a major metabolite of dacarbazine excreted in the urine. AIC is not derived endogenously but from the injected dacarbazine, because the administration of radioactive dacarbazine labeled with 14C in the imidazole portion of the molecule (dacarbazine-2-14C) gives rise to AIC-2-14C.1 Although the exact mechanism of action of dacarbazine for injection is not known, three hypotheses have been offered: Inhibition of DNA synthesis by acting as a purine analog Action as an alkylating agent Interaction with SH groups INDICATIONS AND USAGE Dacarbazine for injection is indicated in the treatment of metastatic malignant melanoma. In addition, dacarbazine for injection is also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other effective agents. CONTRAINDICATIONS Dacarbazine for injection is contraindicated in patients who have demonstrated a hypersensitivity to it in the past. WARNINGS Hemopoietic depression is the most common toxicity with dacarbazine for injection and involves primarily the leukocytes and platelets, although anemia may sometimes occur. Leukopenia and thrombocytopenia may be severe enough to cause death. The possible bone marrow depression requires careful monitoring of white blood cells, red blood cells, and platelet levels. Hemopoietic toxicity may warrant temporary suspension or cessation of therapy with dacarbazine for injection. Hepatic toxicity accompanied by hepatic vein thrombosis and hepatocellular necrosis resulting in death, has been reported. The incidence of such reactions has been low; approximately 0.01% of patients treated. This toxicity has been observed mostly when dacarbazine for injection has been administered concomitantly with other anti-neoplastic drugs; however, it has also been reported in some patients treated with dacarbazine for injection alone.