Adult: For cases except Kaposi's sarcoma and mesothelioma: In combination with doxorubicin: 250 mg/m2 daily via IV infusion over 15-30 minutes for 5 days, then repeated every 3 weeks. Treatment duration is individualised according to the stage of the underlying disease, combination therapy, tolerance, and clinical response. Premedicate with antiemetics prior to administration. Dosage and treatment recommendations may vary among countries or individual products. Refer to detailed product guidelines or local treatment protocols.
Intravenous Hodgkin's disease
Adult: In combination with other antineoplastic agents (e.g. bleomycin, doxorubicin, vinblastine): 150 mg/m2 daily for 5 days, may be repeated every 4 weeks. Alternatively, 375 mg/m2 on Day 1, then repeated every 15 days. Doses may be given via slow IV inj over 1-2 minutes or via IV infusion over 15-30 minutes (particularly for doses ≥200 mg/m2). Treatment duration is individualised according to the stage of the underlying disease, combination therapy, tolerance, and clinical response. Premedicate with antiemetics prior to administration. Dosage and treatment recommendations may vary among countries or individual products. Refer to detailed product guidelines or local treatment protocols.
Intravenous Metastatic malignant melanoma
Adult: 2-4.5 mg/kg daily for 10 days then may be repeated at 4-week intervals, or 200-250 mg/m2 daily for 5 days then may be repeated every 3 weeks. Alternatively, 850 mg/m2 once every 3 weeks. Doses may be given via slow IV inj over 1-2 minutes or via IV infusion over 15-30 minutes (particularly for doses ≥200 mg/m2). Treatment duration is individualised according to the stage of the underlying disease, tolerance, and clinical response. Premedicate with antiemetics prior to administration. Dosage and treatment recommendations may vary among countries or individual products. Refer to detailed product guidelines or local treatment protocols.
Renal Impairment
Dose adjustment may be needed.
Hepatic Impairment
Dose adjustment may be needed.
Reconstitution
IV inj: Reconstitute vials labelled as 100 mg or 200 mg with 9.9 mL or 19.7 mL of sterile water for inj, respectively, to prepare a concentration of 10 mg/mL. IV infusion: Further dilute the reconstituted solution with up to 250 mL dextrose 5% in water or NaCl 0.9% inj. Recommendations for reconstitution and dilution may vary among individual products and between countries (refer to specific product guidelines).
Incompatibility
Incompatible with hydrocortisone Na succinate, Na hydrogen carbonate, and L-cysteine. Incompatible with heparin, particularly for concentrated dacarbazine solutions (25 mg/mL).
Contraindications
Hypersensitivity. Prior severe myelosuppression. Pregnancy and lactation.
Special Precautions
Patients undergoing dental procedures. Bone marrow suppressive effects of dacarbazine may lead to an increased risk of infection, delayed healing, and gingival bleeding; whenever possible, dental works must be completed before treatment initiation or deferred until patient blood counts return to normal. Avoid extravasation. Avoid co-administration with live vaccines. Renal and hepatic impairment.
Adverse Reactions
Significant: Anaphylaxis, anaemia, gastrointestinal effects (e.g. nausea, vomiting, anorexia); tissue damage and severe pain (particularly if extravasation occurs); local inj site pain, burning sensation, and irritation. Eye disorders: Blurred vision. General disorders and administration site conditions: Malaise, influenza-like illness. Investigations: Increased serum creatinine and BUN; increased AST, ALT, alkaline phosphatase, and LDH. Musculoskeletal and connective tissue disorders: Myalgia. Nervous system disorders: Headache, facial paraesthesia, seizures. Psychiatric disorders: Confusion, lethargy. Skin and subcutaneous tissue disorders: Rash, alopecia, urticaria, erythema. Rarely, photosensitivity reactions. Vascular disorders: Facial flushing. Potentially Fatal: Bone marrow suppression (e.g. leucopenia, thrombocytopenia). Rarely, hepatotoxicity accompanied by hepatic vein thrombosis and hepatocellular necrosis.
Women of childbearing potential must use proven birth control methods during therapy. Men with female partners of childbearing potential should use proven birth control methods during treatment and for at least 3 months after stopping the treatment.
Monitoring Parameters
Obtain CBC with differential, LFTs, and renal function tests. Hepatitis B virus screening with HBsAg, hepatitis B core antibody, total Ig or IgG, and antibody to HBsAg is recommended before or at the beginning of systemic chemotherapy. Closely monitor the infusion site. Assess for signs of anaphylactic reactions and renal or hepatic toxicity.
Overdosage
Symptoms: Severe bone marrow suppression, nausea, vomiting, and diarrhoea. Management: Supportive treatment. Administer appropriate transfusions for bone marrow suppression. Monitor haematologic status.
Drug Interactions
Microsomal liver enzyme inducers (e.g. barbiturates, phenytoin, rifampicin) may potentially increase dacarbazine metabolism. Increased risk of acute lung toxicity (particularly adult respiratory distress syndrome) when sequentially administered with fotemustine. May result in enhanced immunosuppressive effects with a risk of lymphoproliferation when given with ciclosporin or tacrolimus. May cause additive bone marrow suppression with other bone marrow depressants. May decrease the therapeutic effect of levodopa. Potentially Fatal: Concurrent administration with live or live-attenuated vaccines may increase the risk of vaccine-associated infections or systemic diseases.
Action
Description: Mechanism of Action: Dacarbazine, an alkylating agent, is a cell-cycle non-specific antineoplastic agent. Its exact mechanism of action has not been fully understood; however, dacarbazine is converted into the active metabolite, 5-(3-methyl-triazeno-1-yl)-imidazole-4-carboxamide (MTIC), which appears to exert its cytotoxic effect by alkylation (methylation) of the deoxyribonucleic acid (DNA) resulting in breaking of DNA double-strand and apoptosis. Pharmacokinetics: Distribution: Rapidly distributed; may be localised in some body tissues, probably the liver. Crosses the blood-brain barrier (limited extent). Plasma protein binding: Approx 5%. Metabolism: Extensively metabolised in the liver via N-demethylation by CYP1A2 and CYP2E1 (and possibly in the tissues by CYP1A1) into the active metabolite, 5-(3-methyl-triazeno-1-yl)-imidazole-4-carboxamide (MTIC); further metabolised into the major metabolite, 5-amino-imidazole-4-carboxamide (AIC). Excretion: Via urine (approx 40% as unchanged drug). Elimination half-life: Biphasic: 19 minutes (initial); approx 5 hours (terminal).
Chemical Structure
Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 135398738, Dacarbazine. https://pubchem.ncbi.nlm.nih.gov/compound/Dacarbazine. Accessed Apr. 25, 2024.
Storage
Intact vial: Store between 2-8°C. Do not freeze. Reconstituted solution: May be stored at 25°C for up to 8 hours or between 2-8°C for up to 24 hours. Diluted solution for IV infusion: Store between 2-8°C for up to 24 hours. Protect intact vial, reconstituted solution, and diluted IV infusion solution from light. Storage and stability recommendations may vary among countries and individual products (refer to specific product guidelines). This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01AX04 - dacarbazine ; Belongs to the class of other alkylating agents. Used in the treatment of cancer.
References
Anon. Dacarbazine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 28/12/2023.Buckingham R (ed). Dacarbazine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/04/2024.Dacarbazine 200 mg, Powder for Solution for Injection (Hospira UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 28/12/2023.Dacarbazine Injection, Powder, for Solution (Fresenius Kabi USA, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 28/12/2023.Dacarbazine. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 20/03/2024.Dacarbazine. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 16/04/2024.DBL Dacarbazine for Injection 200 mg (Hospira Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 28/12/2023.Joint Formulary Committee. Dacarbazine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/12/2023.Pfizer New Zealand Limited. DBL Dacarbazine 200 mg Powder for Injection data sheet 14 November 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 28/12/2023.
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