dacarbazine citrate: clinical use

Prescribing considerations

• Administration should be supervised by clinicians experienced in oncology or haematology.
• Assess gastrointestinal and haematological toxicity before continuing treatment.
• Use particular caution with combined renal and hepatic impairment.
• Prevent extravasation and protect prepared solutions and administration sets from light.
• Discuss contraception, fertility preservation and genetic counselling where relevant.

Contraindications and cautions

• Hypersensitivity to dacarbazine or an excipient.
• Pregnancy or breastfeeding.
• Leukopenia and/or thrombocytopenia.
• Severe liver or kidney disease.
• Further treatment after dacarbazine-associated hepatic veno-occlusive disease.

Monitoring

• Full blood count.
• Liver function and features of hepatic veno-occlusive disease.
• Renal function.
• Infusion site for inflammation or extravasation.
• Signs of infection, bleeding and hypersensitivity.

Clinical pharmacology

A cell-cycle-independent cytostatic prodrug activated in the liver by CYP1A1, CYP1A2 and CYP2E1 to reactive metabolites, including MTIC. DNA methylation inhibits DNA synthesis. Hepatic metabolism and renal excretion contribute to clearance.

Formulation and product differences

• Lower-strength vial presentations are powders for injection or infusion; higher-strength presentations are powders for infusion.
• The powder contains anhydrous citric acid and mannitol; dacarbazine citrate forms in situ.
• Prepared solutions are light-sensitive and for single use. Discoloured solutions or those containing particles must be discarded.
• Solutions are chemically incompatible with heparin, hydrocortisone, L-cysteine and sodium hydrogen carbonate.