More common reactions: Gastrointestinal:
90% of patients experience nausea and vomiting in the first two days of treatment. Diarrhoea may also occur. A degree of tolerance may develop to these effects after about 2 days of treatment. Vomiting lasts 1 to 12 hours. Prophylactic antiemetic therapy with a 5HT3
blocker or dexamethasone is usually required. Rarely, intractable nausea and vomiting have necessitated discontinuance of dacarbazine therapy.
bone marrow depression (25%) (see Life threatening reactions as follows).
Leucocytopenia was usually seen 14 days after commencement of therapy but was noted as early as day 10 and, in 10% of patients, as late as day 30 (i.e., 25 days after completion of therapy). The average length of duration was 1 week and the longest, 3 weeks.
Thrombocytopenia was most frequently seen 18 days after commencement of therapy but in 43% of patients it was noted by day 12 and in 10% not until after day 30. The average length of duration was 1 week and the longest 3 weeks.
Eosinophilia has been reported in one patient receiving dacarbazine.
Less common reactions: Cardiovascular:
facial flushing, ECG abnormalities, orthostatic hypotension. Hypotension appears to be associated with high doses (>850 mg/m2
) of dacarbazine and may be dose-limiting.
(1%, usually transient) rash, alopecia. Photosensitivity reactions have occurred rarely.
(3%) flu-like syndrome with fever to 39°C, severe myalgias and malaise. This syndrome usually occurs after large single doses approximately 7 days after treatment with dacarbazine and lasts 7 to 21 days. It may recur with successive treatments.
(5%, usually transient) Increases in transaminases (AST and ALT), alkaline phosphatase, LDH. Levels usually return to normal within 2 weeks. Hepatic toxicity accompanied by hepatic vein thrombosis and hepatocellular necrosis (Budd-Chiari Syndrome) resulting in death has been reported (see Precautions) (0.01%). A case of acute hepatitis has been reported during the first course of dacarbazine. Granulomatous hepatitis has also occurred.
(3% usually transient) blurred vision, seizures, headache, paraesthesia, confusion, malaise, lethargy.
Injection of concentrated dacarbazine solutions may cause severe pain along the vein. Extravasation of the drug into surrounding tissue may cause severe pain, tissue damage and cellulitis.
Anaphylaxis has occurred occasionally.
Dacarbazine may adversely affect dental procedures (see Precautions).
Dacarbazine may rarely cause stomatitis.
Life threatening reactions: Bone marrow depression:
Death due to agranulocytosis or thrombocytopenia occurred in about 0.4% of patients in clinical trials.
Budd-Chiari Syndrome (see Precautions).