Adult: In combination w/ doxorubicin: 250 mg/m2 once daily by infusion over 15-30 min for 5 days, repeat at 3-wk intervals.
Intravenous Metastatic melanoma
Adult: 2-4.5 mg/kg daily for 10 days, repeat at 4-wk intervals or 200-250 mg/m2 daily via inj over 1 min for 5 days, repeat at 3-wk intervals or 850 mg/m2 via infusion over 15-30 min once every 3 wk.
Intravenous Hodgkin's disease
Adult: In combination w/ doxorubicin, bleomycin and vinblastine (ABVD regimen): 150 mg/m2 daily for 5 days, repeat at 4-wk intervals or 375 mg/m2 via infusion over 15-30 min once every 15 days.
Renal Impairment
Severe: Contraindicated.
Hepatic Impairment
Severe: Contraindicated.
Reconstitution
Reconstitute 100 mg and 200 mg w/ 9.9 mL and 19.7 mL sterile water for inj, respectively, to a concentration of 10 mg/mL. Further dilute for infusion by adding up to 250 mL of dextrose 5% or NaCl 0.9%.
Incompatibility
Incompatible w/ allopurinol, cefepime, piperacillin/tazobactam, heparin, hydrocortisone Na succinate, L-cysteine, Na hydrogen carbonate.
Contraindications
Hypersensitivity. Severe myelosuppression (e.g. leucopenia and/or thrombocytopenia). Severe hepatic or renal impairment. Pregnancy and lactation.
Special Precautions
Hepatic and renal impairment.
Adverse Reactions
Anorexia, vomiting, nausea, rash, alopecia, facial flushing and paraesthesia, orthostatic hypotension, ECG abnormalities, flu-like syndrome, myalgia, malaise, blurred vision, seizure, headache, confusion, lethargy, pain at inj site, tissue damage, cellulitis. Rarely, diarrhoea, photosensitivity, stomatitis. Potentially Fatal: Anaphylaxis, bone marrow suppression (particularly leucopenia and thrombocytopenia), hepatotoxicity accompanied by hepatic vein thrombosis and hepatocellular necrosis.
Monitor CBC w/ differential, leukocyte, erythrocyte and platelet count, LFT; infusion site for extravasation. Assess signs of infection and hepatotoxicity.
Overdosage
Symptoms: Severe bone marrow suppression, nausea, vomiting, diarrhoea. Management: Supportive treatment.
Drug Interactions
Increased metabolism when used w/ enzyme inducers (e.g. barbiturates, rifampicin, phenytoin). May potentiate the effect of mercaptopurine, azathioprine, allopurinol. May impair immune response to vaccines. May enhance the effects of methoxsalen due to photosensitisation.
Food Interaction
Increased hepatotoxic effect w/ alcohol.
Action
Description: Mechanism of Action: Dacarbazine is a non-cell cycle specific antineoplastic agent. The exact mechanism of action by which it exerts cytotoxic effects is still unclear. However, three possible mechanisms have been postulated, including inhibition of DNA synthesis by acting as a purine analog, action as an alkylating agent, and interaction w/ sulfydryl group in the inhibition of bacterial cell growth. Pharmacokinetics: Distribution: Rapidly distributed; localised in some body tissues, probably the liver. Crosses the blood-brain barrier. Volume of distribution: Exceeds total body water content. Plasma protein binding: 5%. Metabolism: Metabolised extensively in the liver by CYP1A2 and CYP2E1 enzymes (and possibly in the tissues by CYP1A1) to 5-(3-methyl-triazeno-1-yl)-imidazole-4-carboxamide (MTIC) which is further metabolised to the major metabolite, 5-amino-imidazole-4-carboxamide (AIC). Excretion: Via urine, approx 40% as unchanged drug. Elimination half-life: Biphasic: 19 min (initial); 5 hr (terminal).
Chemical Structure
Source: National Center for Biotechnology Information. PubChem Database. DTIC-Dome, CID=135398738, https://pubchem.ncbi.nlm.nih.gov/compound/DTIC-Dome (accessed on Jan. 20, 2020)
Storage
Store between 2-8°C. Protect from light. Protect from light. This is a cytotoxic drug, avoid contact w/ skin or mucous membranes by wearing gloves and protective equipment. Wash hands before and after handling. Pregnant staff should not handle this product. Any unused portions should be disposed of in accordance w/ standard procedures.
L01AX04 - dacarbazine ; Belongs to the class of other alkylating agents. Used in the treatment of cancer.
References
Anon. Dacarbazine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/11/2016.Buckingham R (ed). Dacarbazine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/11/2016.Dacarbazine Injection, Powder, for Solution (Hospira Worldwide, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 21/11/2016.Hospira NZ Limited. DBL Dacarbazine for Injection data sheet 29 May 2015. Medsafe. http://www.medsafe.govt.nz. Accessed 21/11/2016.Joint Formulary Committee. Dacarbazine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/11/2016.McEvoy GK, Snow EK, Miller J et al (eds). Dacarbazine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 21/11/2016.
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