Dacarbazine

Indications
 Intravenous
Metastatic melanoma
Adult: 2-4.5 mg/kg daily for 10 days, repeat at 4-wk intervals or 200-250 mg/m2 BSA daily for 5 days, repeat at 3-wk intervals or 850 mg/m2 BSA by infusion, repeat at 3-wk intervals.
Intravenous
Hodgkin's disease
Adult: 150 mg/m2 BSA daily for 5 days, repeat every 4 wk or 375 mg/m2 BSA every 15 days in combination with other agents.
Intravenous
Soft tissue sarcoma
Adult: 250 mg/m2 BSA daily for 5 days repeated every 3 wk. Usually given with doxorubicin.

Incompatibility: Incompatible with hydrocortisone sodium succinate, L-cysteine, sodium hydrogen carbonate and concentrated heparin (25 mg/ml).
Contraindications
 Bone marrow suppression; hypersensitivity.
Warnings / Precautions
 Hepatic or renal impairment. Pregnancy, lactation.
Adverse Reactions
 Leucopenia, thrombocytopenia, anorexia, nausea, diarrhoea, vomiting; flu-like syndrome, myalgia, malaise, facial flushing, paraesthesia, skin reactions, rashes; alopoecia, photosensitivity reactions.
Potentially Fatal: Myelosuppression; hepatotoxicity, anaphylaxis.
Overdose Reactions
 Severe bone marrow suppression and eventually, bone marrow aplasia which may be delayed by up to two wk. It can take 4 wk to reach nadir of leucocytes and thrombocytes. Treatment is supportive with long term careful haematological monitoring. There is no known antidote for dacarbazine overdose.
Drug Interactions
 Impairs immune response to vaccines; possible infection after admin of live vaccines. Effect increased by CYP1A2 inhibitors e.g. amiodarone, ciprofloxacin, fluvoxamine, ketoconazole, lomefloxacin, ofloxacin and rofecoxib. Effect decreased by CYP1A2 inducers e.g. aminoglutethimide, carbamazepine, phenobarbital and rifampicin.
See Below for More dacarbazine Drug Interactions
Mechanism of Actions
 The exact mechanism of action is still unclear but it appears to form methylcarbonium ions that attack nucleophilic groups by attaching to the 7-position of guanine on DNA. It also cross-links DNA strands leading to inhibition of DNA, RNA and protein synthesis.
Absorption: Poorly absorbed from the GI tract (oral).
Distribution: Crosses the blood-brain barrier; localised in the liver. Protein-binding: 5%.
Metabolism: Extensively hepatic.
Excretion: Urine (as unchanged drug). Elimination half-life: 20 min (initial), 5 hr (terminal).
Storage Conditions
 Intravenous: Store at 2-8°C.
ATC Classification
 L01AX04 - dacarbazine ; Belongs to the class of other alkylating agents. Used in the treatment of cancer.
Storage
 Intravenous: Store at 2-8°C.
Available As
  • Dacarbazine 100 mg
  • Dacarbazine 1000 mg
  • Dacarbazine 200 mg
  • Dacarbazine 500 mg

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