NAME OF DRUG
amsacrine

CLASSIFICATION

Cytotoxic Agent - vesicant

ALTERNATE NAMES

m-AMSA, AMSA

INDICATIONS

• induction and maintenance of remission in adult acute leukemia
• some activity has also been shown in Hodgkin's disease and in carcinomas of esophagus, lung and kidney

PHARMACOLOGY

• amsacrine is metabolized extensively in the liver
• inactive metabolites are excreted in the bile
• amsacrine has a biphasic plasma clearance; the terminal half-life after an IV dose is about 6.34 hours in adults

RECONSTITUTION AND STABILITY

• do not refrigerate
• ALL cytotoxic agents are prepared in pharmacy and will be sent to the ward with a label indicating storage conditions and the expiry date.  All cytotoxic waste including bags, sets, tubing, gloves, etc. must be properly disposed of in the cytotoxic waste containers on the nursing unit.

COMPATIBILITY

• DO NOT MIX with NS, potassium chloride or other solutions containing chloride
• compatible with dextrose solutions

ROUTES OF ADMINISTRATION

• CENTRAL ROUTE
  • IV intermittent - dilute in 500 mL D5W and infuse over 60-120 min

VH & HSC ADMINISTRATION POLICY

A - Not to be administered by syringe via the side arm technique.

G - Cytotoxic Agents - See Drug Table G for specific administration guidelines.

H - Central Route: the IV infusion rate must be controlled by an automated infusion control device.

DOSAGE

Dose and schedule depend on protocol and patient response.

Induction:

• as a single agent, it may be given daily for 5-7 days in doses up to 125 mg/m²/day
• the timing of subsequent courses depends on bone marrow recovery and antileukemic effect
• dose may be increased by 20% in the 2nd and subsequent courses if the toxicity has been mild

Maintenance:

• dose should be about 50% of the induction dose, repeated every 4-8 weeks (depending on marrow recovery)

Dosage in renal and hepatic dysfunction:

1. for BUN >7.5 mmol/L or serum creatinine >140 umol/L; decrease dose by 25%
2. for bilirubin >34 umol/L; decrease dose by 25%

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

• pain at the injection and tumor site
• extravasation may lead to tissue necrosis (see appendix VII)

IMPORTANT IMPLICATIONS

• bone marrow depression may be severe and prolonged with the risk of significant anemia, thrombocytopenia and neutropenia. Blood counts should be monitored frequently with supportive measures undertaken as indicated
• arrhythmias may occur if potassium levels are outside of normal range; monitor potassium levels closely during therapy
• transient hepatotoxicity manifested by jaundice and abnormal liver function tests frequently occurs
• GI side effects: nausea, vomiting and diarrhea
• CNS effects:  headaches, confusion, dizziness and rarely seizures
• amsacrine will impart a yellow-orange colour to skin and urine

VGH only:

• Notify security-84 immediately upon accidental spillage.
• DO NOT ATTEMPT CLEAN-UP.
• See also Appendix VI.

Rev. April 2003