amsacrine

Action and Spectrum

Actions and Spectrum  

Actions: 

• Topoisomerase II Inhibition: amsacrine is known for inhibiting topoisomerase II enzymes’ action. Topoisomerases are enzymes that play a crucial role in unwinding DNA during replication and transcription. By inhibiting topoisomerase II, amsacrine prevents the DNA strands from resealing properly after being cut, accumulating DNA breaks and ultimately causing cell death. 
• DNA Intercalation: amsacrine also intercalates with DNA, which means it inserts itself between the base pairs of the DNA double helix. This intercalation disrupts the typical structure of DNA and can interfere with processes like replication and transcription, further contributing to its cytotoxic effects. 

Spectrum: 

amsacrine’s primary use is in the treatment of specific types of cancer. Its spectrum of activity is more focused on hematological malignancies, such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), rather than solid tumors. It has been used as a single agent and with other chemotherapy drugs. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Abdominal pain 

Diarrhea 

Nausea 

Gingivitis 

Vomiting 

Anorexia 

Stomatitis 

Hematuria 

Amnesia 

Frequency not defined 

Atrial fibrillation 

Atrial tachycardia 

Cardiomyopathy (rare) 

Cardiorespiratory arrest 

Bradycardia 

Cardiac failure (rare) 

ECG changes   

Reduced ejection fraction 

Sinus tachycardia 

Hypotension 

Phlebitis 

Tachycardia 

Ventricular premature contractions 

Dizziness 

Ventricular arrhythmia 

Ventricular fibrillation 

Emotional lability 

Lethargy 

Paresthesia 

Headache 

Hypoesthesia 

Seizure 

Weight changes 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• Hypersensitivity 
• Bone marrow suppression  
• Severe liver impairment 
• Severe cardiac dysfunction 

Cautions: 

• Cardiac monitoring 
• Bone marrow suppression 
• Extravasation 
• Renal impairment 
• Pregnancy 
• Lactation 
• Other medications 

Pregnancy / Lactation

Pregnancy consideration:  

amsacrine is contraindicated during pregnancy. 

Breastfeeding warnings:  

The excretion of the drug in breast milk is unknown.  

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

<b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology:  

amsacrine’s primary mode of action is inhibiting topoisomerase II enzymes. Topoisomerases are essential enzymes in regulating DNA structure during replication, transcription, and DNA repair. These enzymes induce reversible breaks in the DNA double helix to allow unwinding of the DNA strands. 

amsacrine inhibits the resealing step of the topoisomerase II-mediated DNA breakage and re-ligation process. Binding to the cleavage complex formed by the enzyme prevents the DNA strands from being properly resealed after being cut. This leads to the accumulation of DNA breaks and ultimately results in cell death.Top of Form 

Pharmacodynamics: The pharmacodynamics of amsacrine refers to how the drug exerts its effects on the body, particularly on the cellular and molecular levels. amsacrine is an antineoplastic agent primarily used to treat certain types of leukemia. Its pharmacodynamics involve interactions with cellular processes and DNA, leading to its anti-cancer effects. Here’s an overview of the pharmacodynamics of amsacrine. 

Pharmacokinetics: 

Absorption 

amsacrine is administered intravenously (IV), which results in immediate and complete bioavailability. Due to the IV route of administration, the drug bypasses any absorption barriers and directly enters the bloodstream. 

Distribution 

amsacrine is distributed widely throughout the body. It has a relatively large distribution volume, indicating that it extensively distributes into tissues beyond the bloodstream. amsacrine is known to cross the blood-brain barrier, allowing it to reach the central nervous system. 

Metabolism 

amsacrine is hepatically metabolized. 

Elimination and Excretion 

The mean half-life is 7.4 hours ranging from 6-10 hours 

Adminstartion

Administration: 

The prepared IV solution of amsacrine is administered through a peripheral vein or a central venous catheter. Central venous catheters are often used for patients requiring frequent IV administration or drugs with a higher risk of irritation to peripheral veins. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: amsacrine 

Pronounced as: am-sac-reen 

Why do we use amsacrine? 

amsacrine is an antineoplastic medication, meaning it is used to treat cancer by inhibiting cancer cells. It does this by interfering with DNA replication and transcription, which are vital for cancer cell growth and division.