Overview
DESCRIPTION Dacarbazine for Injection, USP is a colorless to an ivory colored solid which is light sensitive. Each vial contains 200 mg of dacarbazine (the active ingredient), anhydrous citric acid and mannitol. Dacarbazine is reconstituted and administered intravenously (pH 3.0 to 4.0). Dacarbazine is an anticancer agent.
Mechanism of Action
CLINICAL PHARMACOLOGY After intravenous administration of dacarbazine, 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. In a patient with renal and hepatic dysfunctions, the half-lives were lengthened to 55 minutes and 7.2 hours. The average cumulative excretion of unchanged dacarbazine in the urine is 40% of the injected dose in 6 hours. 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.
Indications
- INDICATIONS AND USAGE Dacarbazine for Injection, USP is indicated in the treatment of metastatic malignant melanoma. In addition, dacarbazine is also indicated for Hodgkin's disease as a second-line therapy when used in combination with other effective agents.
Common Doses
- 4.5 mg
- 250 mg
- 150 mg
- 375 mg
Dosage
DOSAGE AND ADMINISTRATION Malignant Melanoma The recommended dosage is 2 to 4.5 mg/kg/day for 10 days. Treatment may be repeated at 4 week intervals. An alternate recommended dosage is 250 mg/square meter body surface/day I.V. for 5 days. Treatment may be repeated every 3 weeks. Hodgkin's Disease The recommended dosage of dacarbazine in the treatment of Hodgkin's disease is 150 mg/square meter body surface/day for 5 days, in combination with other effective drugs. Treatment may be repeated every 4 weeks.
Black Box Warning
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.
Contraindications
- CONTRAINDICATIONS Dacarbazine is contraindicated in patients who have demonstrated a hypersensitivity to it in the past.
Side Effects
- ADVERSE REACTIONS Symptoms of anorexia, nausea, and vomiting are the most frequently noted of all toxic reactions. Over 90% of patients are affected with the initial few doses. The vomiting lasts 1 to 12 hours and is incompletely and unpredictably palliated with phenobarbital and/or prochlorperazine. Rarely, intractable nausea and vomiting have necessitated discontinuance of therapy with dacarbazine. Rarely, dacarbazine has caused diarrhea. Some helpful suggestions include restricting the patient’s oral intake of food for 4 to 6 hours prior to treatment.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.