Amsacrine

Synonyms: Acridinyl Anisidine, AMSA, m-AMSA

Amsacrine is a 9-anilinoacridine derivative (a derivative of acridine dye) which has antitumour activity by virtue of an ability to bind to DNA by intercalation.¹
It was first synthesised in New Zealand in 1974. It was first used in clinical trials in 1977.²

The mode of action has not been completely elucidated but the ability to intercalate with DNA is thought to cause double strand breaks in DNA and inhibit topoisomerase II. The cytotoxic effect is consequently in the S phase of the cell cycle. The inactive metabolites are excreted in bile (>50%) it is also excreted in faeces and by the kidney.³

Acute leukaemias.³ It is used only occasionally in acute myeloid leukaemia.

It is poorly absorbed orally and is given intravenously. Caution when handling as it is irritant to skin and mucous membranes. Reconstitute using glass apparatus/vials. Local phlebitis can be reduced by infusing slowly over 60-90 minutes and, if phlebitis occurs, by diluting subsequent doses.

• Full blood count. The drug causes myelosuppression.
• ECG: if arrhythmias present seek cardiological opinion.
• Neurological examination. Side effects including headaches and paraesthesia have been reported and pre-existing neuropathies should be excluded.
• Renal function: reduced doses in renal impairment. Fatal arrhythmias with hypokalaemia.
• Liver function: reduced dosage in hepatic impairment.
• Pregnancy testing: contraindicated in pregnancy.

• Common:
  • These are mainly gastrointestinal (particularly nausea and vomiting).
  • Injection site reactions (chemical phlebitis).
  • Myelosuppression peaks at 11-13 days with recovery at 25 days. This can reduce platelets (bruising) and cause anaemia.
  • Mucositis.
• Other side effects include:
  • Discoloured urine. Urine may become orange for 24 hours but this is harmless.
  • Headache.
  • Paraesthesia.
• Less common side effects are:
  • Diarrhoea.
  • Hair loss. This is usually 3-4 weeks after the first dose, but can occur earlier. Hair regrows once treatment stops.
  • Type 1 anaphylactoid hypersensitivity reactions have occurred (rash and pruritis but not hypotension).
  • In association with hypokalaemia fatal arrhythmias have occurred. It is thus important to monitor electrolytes (see below).

Full blood count, urea and electrolytes and liver function. ECG monitoring and neurological examination recommended.

It is initiated in specialist centres.

Shared care protocols may be useful to alert patients and community medical staff to side effects and monitoring requirements.