(British Approved Name, US Adopted Name, rINN)
International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):
Incompatibility. Amsacrine is incompatible with sodium chloride 0.9% injection and with other chloride-containing solutions, apparently because of the poor solubility of the hydrochloride salt in aqueous solution. Amsacrine reacts with certain plastics.
Adverse Effects, Treatment, and Precautions
For a general outline see Antineoplastics.
Bone-marrow depression is usually dose-limiting and may be severe. The nadir of the white cell count has been reported at about 12 days after treatment, with recovery usually by the 25th day. Pancytopenia and haemorrhage may develop. Nausea and vomiting (mild to moderate), stomatitis (mild to life-threatening), rashes, and alopecia may occur. Grand mal seizures, renal dysfunction, hepatotoxicity, and cardiotoxicity have also been reported. Amsacrine is irritant: there may be phlebitis and local tissue necrosis particularly when given in high concentrations. Amsacrine should be given with caution to patients with liver or kidney disease, who may require dosage adjustments.
For a general outline of antineoplastic drug interactions. Use with diuretics or nephrotoxic drugs such as the aminoglycosides may theoretically increase the risk of cardiotoxicity with amsacrine by precipitating hypokalaemia.
Amsacrine is poorly absorbed after oral doses. When given intravenously it has a reported terminal half-life of about 5 to 8 hours. It is metabolised in the liver and excreted primarily in the bile, mostly as metabolites. It is reported to be about 98% protein bound.
Uses and Administration
Amsacrine is an antineoplastic agent that appears to act by intercalation with DNA and inhibition of nucleic acid synthesis. It may also exert an action on cell membranes. Cells in G2 or S phases may be most sensitive to its actions. It is used for the induction and maintenance of remission in adult acute leukaemias, particularly acute myeloid leukaemia. Amsacrine is prepared as a solution in lactic acid and dimethylacetamide, and is given, diluted in glucose 5%, by intravenous infusion over 60 to 90 minutes.
For the induction of remission, amsacrine may be given at a dose of 90 mg/m daily for 5 to 8 days, depending on clinical response. Courses may be repeated at 2- to 4-week intervals according to response, and the dose may be increased to 120 mg/m daily in subsequent courses if tolerated. Maintenance doses of 150 mg/m as a single dose or divided over 3 consecutive days have been given every 3 to 4 weeks, adjusted if necessary according to response.
Complete blood counts should be performed regularly, and cardiac, liver, kidney, and CNS function should be monitored. Doses should be reduced in patients with hepatic or renal impairment (see below).
Administration in hepatic impairment. In moderate to severe hepatic impairment, dosage of amsacrine may need to be reduced by up to 50%. Some licensed product information recommends an initial reduction of 20 to 30%, to a dose between 60 and 75 mg/m daily.
Administration in renal impairment. Inmoderateto severe renal impairment, dosage of amsacrine may need to be reduced by up to 50%. Some licensed product information recommends an initial reduction of 20 to 30%, to a dose between 60 and 75 mg/m daily.
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
Australia: Amsidyl; Belgium: Amsidine; Canada: Amsa PD; Czech Republic: Amsidyl; Denmark: Amekrin; Finland: Amekrin¤; France: Amsalyo; Amsidine¤; Germany: Amsidyl; Ireland: Amsidine; Netherlands: Amsidine; Norway: Amekrin¤; New Zealand: Amsidyl¤; Sweden: Amekrin; Switzerland: Amsidyl; United Kingdom: Amsidine