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Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.

A - Drug Name


SYNONYM(S):   acridinyl anisidide; AMSA; m-AMSA


B - Mechanism of Action and Pharmacokinetics

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.

Oral: yes (poorly absorbed)

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
PPB 97%

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
t ½ ß: 8-9 hours

C - Indications and Status
Health Canada Approvals:

  • Induction of remission in acute adult leukemia refractory to conventional treatment

D - Adverse Effects

Emetogenic Potential:  


Extravasation Potential:   Vesicant

Cardiovascular Arrhythmia (rare, increased with hypokalemia) I
Cardiomyopathy (rare) E
Heart failure (rare) E
Hypotension E
Dermatological Alopecia E
Rash E
Urticaria E
Gastrointestinal Abdominal pain (>10%) E
Anorexia E
Diarrhea (up to 17%) E
GI hemorrhage E
Mucositis (30%) E
Nausea, vomiting (up to 30%) I
Weight changes E
General Fatigue E
Hematological Hemorrhage E
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
Musculoskeletal Myalgia E
Nervous System Confusion E
Dizziness E
Headache E
Paresthesia E
Seizure (rare) E
Renal Proteinuria E
Renal failure (rare) E
Reproductive and breast disorders Infertility L
Respiratory Dyspnea E
Urinary Hematuria E
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.

E - Dosing

Guidelines for dosing include consideration of white blood cell count. Dosage may be reduced and/or delayed in patients with bone marrow depression due to cytotoxic/radiation therapy as well as with renal or hepatic insufficiency.


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

Dosage with Toxicity:


  • Decrease dose by 20% if patient has had life-threatening infection or hemorrhage during the previous course.

Dosage with Hepatic Impairment:




% usual dose

1-2.5x ULN


2-5x ULN


>2.5 x ULN


>5x ULN

reduce further or omit

Dosage with Renal Impairment:

Creatinine Clearance (mL/min) % Usual Dose
40-60 60-75%
<40 OMIT

Dosage in the elderly:

Safety and efficacy have not been established.  Elimination may be slower in the elderly.


Safety and effectiveness have not been established.

F - Administration Guidelines

  • 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

G - Special Precautions

  • 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.

Other Warnings/Precautions:

  • 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:

  • Carcinogenicity: Probable

Pregnancy and Lactation:
  • Clastogenicity: Yes
  • Mutagenicity: Yes
  • Fetotoxicity: Yes
  • Teratogenicity: Yes
    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.
  • Fertility effects: Probable
  • Breastfeeding: Not recommended due to the potential secretion into breast milk.
H - Interactions

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.

I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

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

K - References

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

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.