Dacarbazine


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IV Metastatic melanoma 2-4.5 mg/kg/day for 10 days, repeat at 4-wk intervals or 200-250 mg/m2/day via inj for 5 days, repeat at 3-wk intervals, or 850 mg/m2 via infusion once every 3 wk. Hodgkin's disease In combination w/ other agents: 150 mg/m2/day for 5 days, repeat at 4-wk intervals or 375 mg/m2 once every 15 days. Soft tissue sarcoma In combination w/ doxorubicin: 250 mg/m2 once daily for 5 days, repeat at 3-wk intervals.
Dosage Details
Intravenous
Soft tissue sarcoma
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.
IV/Parenteral: C
Patient Counseling Information
May impair ability to drive or operate machinery.
MonitoringParameters
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: 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

Chemical Structure Image

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.
ATC Classification
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.

Disclaimer: This information is independently developed by MIMS based on Dacarbazine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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