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Black Box Warning
See full prescribing information for complete Boxed Warning.
Dacarbazine is an antineoplastic agent and alkylating agent that is FDA approved for the treatment of metastatic malignant melanoma and also indicated for Hodgkin's disease as a secondary-line therapy when used in combination with other effective agents.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include anorexia, nausea, and vomiting, influenza-like syndrome of fever to 39°C, myalgias, malaise and alopecia.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Metastatic malignant melanoma
- Dacarbazine for injection is indicated in the treatment of metastatic malignant melanoma.
- The recommended dosage is 2 to 4.5 mg/kg/day for 10days.Treatment may be repeated at 4 week intervals.
- An alternate recommended dosage is 250 mg/square meter body surface/day IV for 5 days. Treatment may be repeated every 3 weeks.
- 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.
- The recommended dosage of dacarbazine for injection 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.5 An alternative recommended dosage is 375 mg/square meter body surface on day 1, in combination with other effective drugs, to be repeated every 15 days.
- Dacarbazine for injection 200 mg/vial is reconstituted with 19.7 mL of sterile water for injection, USP. Dacarbazine for injection 500 mg/vial is reconstituted with 49.25 mL of sterile water for injection, USP. The resulting solution contains 10 mg/mL of dacarbazine having a pH of 3.0 to 4.0. The calculated dose of the resulting solution is drawn into a syringe and administered only intravenously.
- The reconstituted solution may be further diluted with 5% dextrose injection or sodium chloride injection and administered as an intravenous infusion.
- After reconstitution and prior to use, the solution in the vial may be stored at 4°C for up to 72 hours or at normal room conditions (temperature and light) for up to 8 hours. If the reconstituted solution is further diluted in 5% dextrose injection or sodium chloride injection, the resulting solution may be stored at 4°C for up to 24 hours or at normal room conditions for up to 8 hours.
- Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.7–12 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Off-Label Use and Dosage (Adult)
There is limited information regarding Off-Label Guideline-Supported Use of dacarbazine in adult patients.
- Cyclophosphamide 750 mg/square meter (m(2)) and vincristine 1.4 mg/m(2) on day 1, and dacarbazine 400 mg/m(2) on days 1 and 2; all were given intravenously and repeated every 21 days.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of dacarbazine in pediatric patients.
Off-Label Use and Dosage (Pediatric)
There is limited information regarding Off-Label Guideline-Supported Use of dacarbazine in pediatric patients.
There is limited information regarding Off-Label Non–Guideline-Supported Use of dacarbazine in pediatric patients.
- Dacarbazine for injection is contraindicated in patients who have demonstrated a hypersensitivity to it in the past.
See full prescribing information for complete Boxed Warning.
- [Bone marrow suppression
Clinical Trials Experience
- 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 1–12 hours and is incompletely and unpredictably palliated with phenobarbital and/or prochlorperazine. Rarely, intractable nausea and vomiting have necessitated discontinuance of therapy with dacarbazine for injection. Rarely, dacarbazine for injection has caused diarrhea. Some helpful suggestions include restricting the patient's oral intake of food for 4–6 hours prior to treatment. The rapid toleration of these symptoms suggests that a central nervous system mechanism may be involved, and usually these symptoms subside after the first 1 or 2 days.
- There are a number of minor toxicities that are infrequently noted. Patients have experienced an influenza-like syndrome of fever to 39°C, myalgias and malaise. These symptoms occur usually after large single doses, may last for several days, and they may occur with successive treatments.
- Alopecia has been noted as has facial flushing and facial paresthesia. There have been few reports of significant liver or renal function test abnormalities in man. However, these abnormalities have been observed more frequently in animal studies.
- Erythematous and urticarial rashes have been observed infrequently after administration of dacarbazine for injection. Rarely, photosensitivity reactions may occur.
There is limited information regarding Postmarketing Experience of dacarbazine in the drug label.
There is limited information regarding Dacarbazine Drug Interactions in the drug label.
Use in Specific Populations
- Dacarbazine for injection has been shown to be teratogenic in rats when given in doses 20 times the human daily dose on day 12 of gestation. Dacarbazine when administered in 10 times the human daily dose to male rats (twice weekly for 9 weeks) did not affect the male libido, although female rats mated to male rats had higher incidence of resorptions than controls. In rabbits, dacarbazine daily dose 7 times the human daily dose given on days 6–15 of gestation resulted in fetal skeletal anomalies. There are no adequate and well controlled studies in pregnant women. *Dacarbazine for injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of dacarbazine in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of dacarbazine during labor and delivery.
- It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for dacarbazine for injection in animal studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
There is no FDA guidance on the use of dacarbazine with respect to pediatric patients.
There is no FDA guidance on the use of dacarbazine with respect to geriatric patients.
There is no FDA guidance on the use of dacarbazine with respect to specific gender populations.
There is no FDA guidance on the use of dacarbazine with respect to specific racial populations.
There is no FDA guidance on the use of dacarbazine in patients with renal impairment.
There is no FDA guidance on the use of dacarbazine in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of dacarbazine in women of reproductive potentials and males.
There is no FDA guidance one the use of dacarbazine in patients who are immunocompromised.
Administration and Monitoring
There is limited information regarding Monitoring of dacarbazine in the drug label.
There is limited information regarding IV Compatibility of dacarbazine in the drug label.
Give supportive treatment and monitor blood cell counts.
Mechanism of Action
- Although the exact mechanism of action of dacarbazine for injection is not known, three hypotheses have been offered:
- 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:
There is limited information regarding Pharmacodynamics of dacarbazine in the drug label.
- 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
- Carcinogenicity of dacarbazine was studied in rats and mice. Proliferative endocardial lesions, including fibrosarcomas and sarcomas were induced by dacarbazine in rats. In mice, administration of dacarbazine resulted in the induction of angiosarcomas of the spleen.
There is limited information regarding Clinical Studies of dacarbazine in the drug label.
Store in a refrigerator 2°C to 8°C (36°F to 46°F). Use within 8 hours of reconstitution. Protect from light.
Package and Label Display Panel
Patient Counseling Information
There is limited information regarding Patient Counseling Information of dacarbazine in the drug label.
Precautions with Alcohol
- Alcohol-dacarbazine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Look-Alike Drug Names
- A® — B®
The contents of this FDA label are provided by the National Library of Medicine.
- Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R; et al. (1988). "Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine.". Ann Intern Med. 109 (4): 267–73. PMID 3395037.