dexrazoxane

Action and Spectrum

Mechanism of action 

It is a cardioprotective agent that reduces the cardiac toxicity associated with anthracycline chemotherapy. The mechanism of action of dexrazoxane is not fully understood. Still, it is thought to act by chelating iron and inhibiting the formation of reactive oxygen species (ROS) that can damage DNA and lead to cardiac toxicity. 

Spectrum 

The spectrum of activity of dexrazoxane is limited to reducing the cardiac toxicity associated with anthracycline chemotherapy. It is not active against cancer cells. 

Drug Interaction

Adverse Reaction

Frequency undefined:  

Phlebitis 

Pain at the injection site 

Increased myelosuppression 

Black Box Warning

Contraindication / Caution

Contraindications 

• Hypersensitivity to dexrazoxane or any of its excipients 
• Pregnancy 
• Lactation 
• Children under the age of 6 years 
• Patients with known or suspected impaired cardiac function 
• Patients with known or suspected impaired hepatic function 
• Patients with known or suspected impaired renal function 
• Patients with known or suspected impaired bone marrow function 
• Patients receiving concurrent treatment with other cardiotoxic or myelotoxic agents 

Caution 

• It should be used with caution in patients with a history of cardiac disease, as it may exacerbate these conditions.  
• It should also be used with caution in patients with renal impairment, as it may accumulate in the body and cause toxicity.  
• Additionally, dexrazoxane may increase the risk of secondary malignancies when combined with anthracycline chemotherapy.  
• Patients should be closely monitored for signs of cardiac toxicity or secondary malignancy during and after treatment with dexrazoxane 

Pregnancy / Lactation

Pregnancy consideration: may cause foetal harm when administered during pregnancy 

Lactation: Excretion of the drug in human 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.   

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 available 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: There is no data available for the drug under this category 

Pharmacology

Pharmacology 

It is a chelating agent that reduces the cardiac toxicity associated with anthracycline chemotherapy. It is a prodrug converted to its active form, ADR-529, by hydrolysis in the liver. The active form of dexrazoxane binds to iron, which reduces the formation of reactive oxygen species (ROS) that can damage DNA and lead to cardiac toxicity 

Pharmacodynamics 

The pharmacodynamics of dexrazoxane involves its ability to chelate iron and inhibit the formation of reactive oxygen species (ROS). These ROS can damage DNA and lead to cardiac toxicity when anthracycline chemotherapy is used. By binding to iron and reducing the formation of these ROS, dexrazoxane can protect the heart from the toxic effects of anthracyclines. 

The active form of dexrazoxane, ADR-529, is thought to act by binding to the iron in the mitochondrial enzymes. This binding reduces the ability of these enzymes to generate ROS, which in turn reduces the amount of DNA damage and cardiac toxicity 

Pharmacokinetics 

Absorption: 

It is administered intravenously (IV) and is rapidly and completely absorbed. The half-life of dexrazoxane is 2-2.5 hours; it reaches peak plasma concentrations of 36.5 mcg/mL within the first hour after IV administration and is not protein bound. 

Distribution:  

It distributes widely in the body, with the highest concentrations in the liver, heart, and kidney. The volume of distribution (Vd) of dexrazoxane is 22.4 L/m² 

Metabolism:  

It is rapidly metabolized in the liver and excreted in the urine  

Excretion:  

The elimination half-life of dexrazoxane is about 2 hours. It is cleared from the body primarily through renal excretion with a renal clearance of 3.35L/hr/sq.meter;  approximately 42% of the drug is excreted in the urine 

Adminstartion

Administration 

Intravenous administration 

Do not combine any medications 

Induced cardiomyopathy by doxorubicin 

Give IV pushes without pushing.15 minutes before giving doxorubicin, IV infuse the final diluted solution.After the dexrazoxane infusion is finished, give the doxorubicin within 30 minutes. 

Extravasation 

• For adequate blood flow to the extravasation location, remove cooling techniques (such as ice packs) from the area at least 15 minutes prior to delivery. 
• Using a large diameter vein in an extremity or location different than the one where the extravasation occurred, administer the final diluted solution IV over a period of 1-2 hours at room temperature and under normal lighting circumstances. 
• Start the treatment on Days 2 and 3 at the same time (+/- 3 hours) as on Day 1. 
• After treatment and until resolution, routinely check for extravasation. 

Storage 

Zinecard 

Unused vials should be stored at 20-25ºC (68-77ºF), with excursions permitted to 15-30ºC (59-86ºF) and protected from light. The vial should be kept in its carton until ready for use. Reconstituted vials are stable for 30 minutes at room temperature or up to 3 hours when refrigerated at 2-8ºC (36-46ºF) and have a pH of 1 to 3. Reconstituted solution should be used immediately after further dilution, or if not used immediately, it is stable for 4 hours from the time of preparation when stored at room temperature or for up to 12 hours when refrigerated at 2-8ºC (36-46ºF) 

Extravasation use: Infusion solutions have a pH of 3.5 to 5.5  

Totect 

Unused vials should be stored at 20-25ºC (68-77ºF), with excursions permitted to 15-30ºC (59-86ºF) and protected from light. The vial should be kept in its carton until ready for use. Reconstituted vials are stable for 30 minutes at room temperature. The reconstituted solution should be used immediately after further dilution, or if not used immediately, it is stable for 4 hours from the time of preparation when stored at room temperature or for up to 12 hours when refrigerated between 2-8ºC (36-46ºF).  

Extravasation use: Infusion solutions have a pH of 3.5 to 5.5 

Patient Information Leaflet

Patient information leaflet 

Generic Name: dexrazoxane 

Pronounced: [ dex-ray-ZOX-ane ] 

Why do we use dexrazoxane? 

It is a cytoprotective drug used to prevent and treat cardiomyopathy caused by doxorubicin treatment for metastatic breast cancer