SYNONYM(S): acridinyl anisidide; AMSA; m-AMSA
COMMON TRADE NAME(S): AMSA P D® (Erfa)
Amsacrine is an acridine dye derivative. The mechanism of action is incompletely defined but amsacrine appears to be a DNA intercalator. It causes double-strand breaks in DNA, and inhibits topoisomerase II, leading to S phase and G2 arrest. Cytotoxicity is greatest when cells are cycling.
To all tissues except the brain. High initial concentrations in liver, spleen and kidney.
|Cross blood brain barrier?||Trace|
|Volume of distribution||1.67 L/kg; 87.1 L/m2|
Pharmacokinetics are dose dependent. Amsacrine is metabolized extensively in the liver to amsacrine-glutathione conjugate
|Active metabolites||None known|
|Inactive metabolites||Yes, in bile|
Primarily excreted in bile; about 80% in feces within 48 hours.
|Urine||35% within 72 hours; 20% as intact drug|
t ½ α: 10-15 minutes
- Induction of remission in acute adult leukemia refractory to conventional treatment
Extravasation Potential: Vesicant
|ORGAN SITE||SIDE EFFECT* (%)||ONSET**|
|Cardiovascular||Arrhythmia (rare, increased with hypokalemia)||I|
|Heart failure (rare)||E|
|Gastrointestinal||Abdominal pain (>10%)||E|
|Diarrhea (up to 17%)||E|
|Nausea, vomiting (up to 30%)||I|
|Myelosuppression (100%) (nadir 11-13 days, recovery 17-25 days)||E|
|Hepatobiliary||↑ LFTs (may be severe)||E|
|Hypersensitivity||Drug reaction (rare, type 1 anaphylactoid)||I|
|Infection||Sepsis (and fever)||E|
|Injection site||Phlebitis (chemical)||I|
|Metabolic / Endocrine||Hyperuricemia (tumour lysis)||I|
|Renal failure (rare)||E|
|Reproductive and breast disorders||Infertility||L|
|Urine discoloration (orange)||E|
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.
** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)
The major side effects are myelosuppression and stomatitis. Myelosuppression has a rapid onset and usually persists for 3 weeks after administration.
The tissue necrosis that occurs with extravasation may occur weeks to months after the treatment. Patients must be observed for delayed reactions and prior injection sites carefully inspected.
Hyperuricemia during periods of active cell lysis can be minimized with allopurinol and hydration. In hospitalized patients the urine may be alkalinized, by addition of sodium bicarbonate to the IV fluids, if tumour lysis is expected.
Cardiotoxicity is unusual, although arrhythmias (including QT prolongation) have been documented and occur in about 1% of patients who have not received prior chemotherapy. It does not appear to be dose-dependent. Thirty percent of patients experiencing arrhythmias had hypokalemia. Patients who have had underlying cardiac disease, had received prior mediastinal radiation or had previous exposure to anthracyclines may be at increased risk for cardiotoxicity. The manufacturer recommends monitoring of cardiac rhythm during and after drug administration.
Phlebitis can be reduced by infusing the diluted drug over a period of 60-120 minutes, or by giving it through a central venous line.
Type I hypersensitivity reactions have been reported with rash, pruritus and erythema on the first dose of amsacrine. No hypotension was reported. Rashes have also been reported among laboratory personnel who handle bulk drugs suggesting a Type IV skin-sensitizing process.
Intravenous: 75-125 mg/m² Daily x 5 days
- Two courses may be necessary to achieve induction. The second course should not be administered until recovery of myelosuppression, unless marrow infiltration is persistent. Increase by 20% in the second and each subsequent course if no significant toxicity in the preceding course, and if marrow hypoplasia has not been achieved
- 50% of induction dose depending on peripheral blood counts every 4-8 weeks
- Decrease dose by 20% if patient has had life-threatening infection or hemorrhage during the previous course.
% usual dose
>2.5 x ULN
reduce further or omit
|Creatinine Clearance (mL/min)||% Usual Dose|
- Dilute only with supplied lactic acid diluent.
- May use glass syringe to withdraw drug from the ampoule to the vial. If a plastic syringe is used, the drug should not remain in the syringe for more than 15 minutes.
- Dilute further in 500mL bag of Dextrose 5%. Do not dilute with Normal Saline.
- For IV infusion only. Infuse over 60-90 minutes.
- Incompatible with any solution containing chloride ions
- in patients who are hypersensitive to amsacrine or to acridine derivatives (e.g., acriflavine), or to any ingredients in the formulation.
- in patients who have pre-existing drug-induced or radiotherapy-induced bone marrow suppression.
- Avoid concomitant use of live vaccines.
- The risk of arrhythmia may be increased in hypokalemia, concomitant use of diuretics, other nephrotoxic drugs or previous anthracycline treatment.
- Fluid or electrolyte imbalance should be corrected before starting amsacrine. Ensure serum potassium level is normal immediately before and during amsacrine infusion.
Other Drug Properties:
Amsacrine's safe use in pregnancy has not been established. Adequate contraception should be used by both sexes, during treatment and for at least 6 months after the last dose. Men should also be advised not to father a child during treatment.
- Breastfeeding: Not recommended due to the potential secretion into breast milk.
Insufficient data are available to prove or disprove interactions.
Amsacrine is highly protein bound and the potential exists for interactions when co-administering other highly protein bound drugs.
Avoid the concomitant administration of live vaccines.
Amsacrine does not appear to increase the risk of doxorubicin-induced cardiac toxicity.
|Monitor Type||Monitor Frequency|
|Liver function tests||Baseline and regular|
|Renal function tests (including uric acid and electrolytes)||Baseline and regular|
|CBC||Baseline and frequent|
|Cardiac rhythm||during and after administration|
|Clinical monitoring for infection, bleeding, mucositis, diarrhea, nausea/vomiting, infusion site reactions||regular|
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
AMSA P D® (product monograph). Westmount, Quebec: Erfa Canada Inc; 16 August 2010.
Cassileth PA, Gale RP. Amsacrine: a review. Leuk Res. 1986;10(11):1257-65.
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Amsacrine. International Agency for Research on Cancer 2000; Volume 16, p. 317.
Louie AC, Issell BF. Amsacrine (AMSA)--a clinical review. J Clin Oncol 1985;3(4):562-92.
Paxton JW, Jurlina JL, Foote SE. The binding of amsacrine to human plasma proteins. Journal of Pharmacy and Pharmacology 1986; 38(6); 432-8.
Weiss RB, Grillo-Lopez AJ, Marsoni S, et al. Amsacrine-associated cardiotoxicity: an analysis of 82 cases. J Clin Oncol 1986;4:918-28.
September 2011: Entire document revision
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