Totect

Mechanism of Action

Dexrazoxane has a dual mechanism of action1

#1 Mechanism of Action1,2

Dexrazoxane is a catalytic inhibitor of topoisomerase II – the enzyme which regulates DNA formation, and allows cells to replicate.

MOA DNA Strand / Anthracycline MOA Dexrazoxane / Topoisomerase
Anthracyclines attack cancer cells, damaging them and preventing them from replicating, with the aim of killing the cell. Anthracyclines are topoisomerase II poisons, targeting this essential enzyme and preventing the cell from replicating. As a catalytic inhibitor of topoisomerase II, dexrazoxane, blocks the action of anthracyclines.

#2 Mechanism of Action3

Dexrazoxane is an iron chelation drug. By binding to iron complexes (Fe3+) before anthracyclines enter cells, dexrazoxane prevents the formation of the Fe- anthracycline complex. This prevents free radical release.1

Method of Action #2

While dexrazoxane reverses the tissue damage associated with anthracycline extravasations, it does not interfere with the anti-tumor effect of these agents.

 

References:
1. Langer SW, Sehested M, and Jensen PB. Anthracycline extravasation: a comprehensive review of experimental and clinical treatments. Tumori 2009; 95(3): 273-82. 2. Roe H. Anthracycline extravasations: prevention and management. Br J Nurs 2011; 20(17): S16, S18-22. 3. Hasinoff BB and Herman, EH. Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug? Cardiovasc Toxicol 2007; 7: 140-144.

INDICATION: TOTECT® (dexrazoxane) is indicated for the treatment of extravasation resulting from intravenous anthracycline chemotherapy.

IMPORTANT DOSAGE AND ADMINISTRATION INSTRUCTIONS
Reconstitute and further dilute Totect before use [see Prescribing Information- Dosage and Administration]. The Totect dose should be reduced by 50% in patients with creatinine clearance values < 40 mL/min.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS
Myelosuppression: TOTECT is associated with leukopenia, neutropenia, and thrombocytopenia. Perform hematological monitoring during treatment with TOTECT and cytotoxic chemotherapy as the myelosuppression and cytotoxic potential may be additive to that of chemotherapy alone.

Anaphylactic/Hypersensitivity Reactions: Hypersensitivity reactions including anaphylactic reaction, angioedema, skin reactions, bronchospasm, respiratory distress, hypotension and loss of consciousness have occurred in patients treated with dexrazoxane products and anthracyclines. Previous history of allergy to dexrazoxane products should be carefully considered prior to administration. Consider permanent discontinuation in patients with severe hypersensitivity reactions.

Embryo-Fetal Toxicity: TOTECT can cause fetal harm when administered to a pregnant woman. Advise patients of potential risk and to use effective contraception during treatment and 6 months following the last dose of TOTECT. Use in patients with hepatic impairment is not recommended.

DRUG INTERACTIONS
TOTECT is not recommended for use with dimethyl sulfoxide (DMSO).

ADVERSE REACTIONS
In the clinical studies, TOTECT was administered to patients also receiving chemotherapeutic agents for cancer, and the adverse reaction profile reflects the combination of TOTECT, underlying disease, and already administered chemotherapy. The most common adverse reactions (≥15%) are nausea, fever, injection site pain, vomiting, and postoperative infection.

Click here to view Full Prescribing Information