DACARBAZINE- dacarbazine injection, powder, for solution
APP Pharmaceuticals, LLC
WARNING
It is recommended that dacarbazine be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents.
1. Hemopoietic depression is the most common toxicity with dacarbazine (see WARNINGS).
2. Hepatic necrosis has been reported (see WARNINGS).
3. Studies have demonstrated this agent to have a carcinogenic and teratogenic effect when used in animals.
4. In treatment of each patient, the physician must weigh carefully the possibility of achieving therapeutic benefit against the risk of toxicity.
DESCRIPTION
Dacarbazine for Injection, USP is a white to pale yellow colored solid which is light sensitive. Each vial contains 100 mg of dacarbazine, or 200 mg of dacarbazine (the active ingredient), anhydrous citric acid and mannitol. Dacarbazine for Injection, USP is reconstituted and administered intravenously (pH 3-4). Dacarbazine for Injection, USP is an anticancer agent. Chemically, dacarbazine is 5-(3,3-Dimethyl-1-triazeno) imidazole-4-carboxamide with the following structural formula:
dacarbazine-structure
(click image for full-size original)
M.W. 182.19 C6 H10 N6 O
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 for injection 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 14 C in the imidazole portion of the molecule (dacarbazine-2-14 C) gives rise to AIC-2-14 C.1
Although the exact mechanism of action of dacarbazine is not known, three hypotheses have been offered:
1. inhibition of DNA synthesis by acting as a purine analog
2. action as an alkylating agent
3. 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 second-line therapy when used in combination with other effective agents.
