Dacarbazine
Pronunciation: (da-CAR-buh-zeen)Class: Alkylating agent, Triazine
Trade Names:
DTIC-Dome
- Powder for injection 100 mg
- Powder for injection 200 mg
Pharmacology
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Exact mechanism is unknown. Three mechanisms are hypothesized: 1) inhibition of DNA synthesis by acting as a purine analog; 2) action as an alkylating agent; and 3) interaction with sulfhydryl groups.
Pharmacokinetics
Distribution
Vd exceeds total body water content, suggesting localization in some body tissue, probably liver. Not appreciably bound to proteins.
Metabolism
Extensive major metabolite is 5-amino-imidazole-4 carboxamide.
Elimination
Biphasic, initial t ½ is 19 min and terminal t ½ is 5 h; 40% excreted unchanged in urine in 6 h.
Special Populations
Hepatic Function ImpairmentInitial t ½ increased to 55 min and terminal t ½ increased to 7.2 h in a patient with renal and hepatic function impairment.
Indications and Usage
Treatment of metastatic malignant melanoma; in combination with other agents as second-line therapy for Hodgkin disease.
Unlabeled Uses
In combination with cyclophosphamide and vincristine for malignant pheochromocytoma; in combination with other agents for treatment of advanced metastatic soft tissue sarcoma; alone or in combination with other agents for management of Kaposi sarcoma.
Contraindications
Standard considerations.
Dosage and Administration
Malignant MelanomaAdults
IV 2 to 4.5 mg/kg/day for 10 days is recommended; may be repeated at 4 wk intervals. Alternatively, administer 250 mg/m 2 daily for 5 days; may be repeated every 3 wk.
Hodgkin DiseaseAdults
IV 150 mg/m 2 daily for 5 days in combination with other effective drugs is recommended; may be repeated every 4 wk. Alternatively, 375 mg/m 2 on day 1 in combination with other effective drugs, repeated every 15 days.
General Advice
- Follow institutional and NIH procedures for handling, administration, and disposal of anticancer drugs.
- Reconstitute 100 mg vial with 9.9 mL sterile water for injection. Reconstitute 200 mg vial with 19.7 mL sterile water for injection. Resulting solution contains 10 mg/mL of dacarbazine.
- Reconstituted solution may be further diluted with dextrose 5% injection or sodium chloride injection for administration as an IV infusion.
- To reduce GI adverse reactions, restrict the patient's food intake for 4 to 6 h prior to treatment if possible.
Storage/Stability
Store unopened vials in refrigerator (36° to 46°F). Protect from light. Store reconstituted solution in vial at 39.2°F for up to 72 h or at normal room conditions for up to 8 h. If reconstituted solution is further diluted with dextrose 5% injection or sodium chloride injection, store diluted solution at 39.3°F for up to 24 h or at normal room conditions for up to 8 h.
Drug Interactions
None well documented.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Dermatologic
Alopecia; facial flushing; erythematous and urticarial rashes.
GI
Anorexia, nausea, vomiting (over 90% with initial few doses).
Hematologic
Bone marrow suppression.
Lab Tests
Abnormal liver or renal function tests.
Musculoskeletal
Myalgia.
Miscellaneous
Flu-like syndrome; malaise; facial paresthesia.
Precautions
WarningsAdminister under supervision of a qualified physician experienced in use of cancer chemotherapeutic agents; hemopoietic depression is most common toxicity; hepatic necrosis has been reported; carcinogenic and teratogenic effects demonstrated in animals; weigh possibility of achieving therapeutic benefit against risk of toxicity when treating patient. |
MonitorEnsure that CBC with differential and platelet count is evaluated before starting therapy and then frequently during therapy. Implement infection control measures if WBC drops; implement bleeding precautions if platelet count drops. Assess injection site frequently for signs or symptoms of extravasation (eg, burning, pain, induration). Monitor patient for signs and symptoms of bacterial, viral, or fungal infection. |
Pregnancy
Category C .
Lactation
Undetermined.
Hemopoietic depression
Hemopoietic depression is the most common toxicity and involves primarily leukocytes and platelets, although anemia sometimes occurs. Leukopenia and thrombocytopenia may be severe enough to cause death. Possible bone marrow suppression requires careful monitoring of RBC, WBC, and platelets.
Hepatotoxicity
Hepatotoxicity, accompanied by hepatic vein thrombosis and hepatocellular necrosis resulting in death, may occur.
Vomiting
Consider using phenobarbital and/or prochlorperazine for recurrent or prolonged vomiting.
Overdosage
Symptoms
Bone marrow suppression.
Patient Information
- Advise patient, family, or caregiver that medication will be prepared and administered by health care providers in a health care setting.
- Advise patient, family, or caregiver that medication may be used in combination with other agents, including antiemetics and sedatives, to achieve max benefit possible.
- Advise patient, family, or caregiver that restricting food intake for 4 to 6 h before treatment may help reduce nausea and vomiting.
- Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; difficulty breathing; fever, chills, or other signs of infection; unusual bleeding or bruising; pain, redness, or swelling at injection site.
- Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea, or appetite loss; persistent or worsening general body weakness.
- Advise patient, family, or caregiver that hair loss is a common adverse reaction of therapy, but that this is usually reversible after therapy has been completed.
- Caution women of childbearing potential to avoid becoming pregnant during therapy.
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More Dacarbazine resources
dacarbazine Intravenous, Injection - Includes detailed dosage instructions.
