Totect

Totect Uses, Dosage, Side Effects, Food Interaction and all others data.

An antimitotic agent with immunosuppressive properties. Totect, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. [PubChem]The Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy.

Totect is a cardioprotective agent for use in conjunction with doxorubicin indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage.

Trade Name Totect
Availability Prescription only
Generic Dexrazoxane
Dexrazoxane Other Names Dexrazoxan, Dexrazoxane, Dexrazoxano, Dexrazoxanum, Dextrorazoxane
Related Drugs hyaluronidase, Zinecard, Amphadase, Hylenex, Vitrase, Hydase
Weight 250mg, 500mg,
Type Intravenous powder for injection
Formula C11H16N4O4
Weight Average: 268.2691
Monoisotopic: 268.11715502
Protein binding

Very low (< 2%)

Groups Approved, Withdrawn
Therapeutic Class
Manufacturer
Available Country United States,
Last Updated: September 19, 2023 at 7:00 am
Totect
Totect

Uses

Totect is a cytoprotective drug used to prevent and improve cardiomyopathy associated with doxorubicin treatment for metastatic breast cancer.

For reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines.

Totect is also used to associated treatment for these conditions: Cardiomyopathy

How Totect works

The mechanism by which dexrazoxane exerts its cardioprotective activity is not fully understood. Totect is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II.

Toxicity

Intraperitoneal, mouse LD10 = 500 mg/kg. Intravenous, dog LD10 = 2 gm/kg.

Food Interaction

No interactions found.

Volume of Distribution

  • 9 to 22.6 L/m^2

Elimination Route

IV administration results in complete bioavailability.

Half Life

2.5 hours

Clearance

  • 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Totect]
  • 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Totect]

Elimination Route

Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of dexrazoxane was excreted in the urine.

Innovators Monograph

You find simplified version here Totect

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http://classyfire.wishartlab.com/tax_nodes/C0002239
http://classyfire.wishartlab.com/tax_nodes/C0004139
http://classyfire.wishartlab.com/tax_nodes/C0004557
http://classyfire.wishartlab.com/tax_nodes/C0003940
http://classyfire.wishartlab.com/tax_nodes/C0004150
http://classyfire.wishartlab.com/tax_nodes/C0001831
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50223
http://www.hmdb.ca/metabolites/HMDB0014524
http://www.genome.jp/dbget-bin/www_bget?drug:D03730
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=71384
https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505982
https://www.chemspider.com/Chemical-Structure.64479.html
https://mor.nlm.nih.gov/RxNav/search?searchBy=RXCUI&searchTerm=42736
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=50223
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL1738
https://zinc.docking.org/substances/ZINC000087515509
http://bidd.nus.edu.sg/group/cjttd/ZFTTDDRUG.asp?ID=DAP000649
http://www.pharmgkb.org/drug/PA449259
https://www.ebi.ac.uk/pdbe-srv/pdbechem/chemicalCompound/show/CDX
http://www.rxlist.com/cgi/generic2/dexrazoxane.htm
https://www.drugs.com/cdi/dexrazoxane.html
https://en.wikipedia.org/wiki/Dexrazoxane
*** Taking medicines without doctor's advice can cause long-term problems.
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