Dexrazoxane
File:Dexrazoxane.svg | |
Systematic (IUPAC) name | |
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4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
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Clinical data | |
AHFS/Drugs.com | monograph |
MedlinePlus | a609010 |
Identifiers | |
CAS Number | 24584-09-6 |
ATC code | V03AF02 (WHO) |
PubChem | CID: 71384 |
IUPHAR/BPS | 7330 |
DrugBank | DB00380 |
ChemSpider | 64479 |
UNII | 048L81261F |
KEGG | D03730 |
ChEBI | CHEBI:50223 |
ChEMBL | CHEMBL1738 |
Chemical data | |
Formula | C11H16N4O4 |
Molecular mass | 268.269 g/mol |
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Dexrazoxane hydrochloride (Zinecard by Pfizer in USA and Canada; Cardioxane by Novartis for EU and other countries) is a cardioprotective agent. It was discovered by Kurt Hellmann in 1972. Dexrazoxane is a sterile, pyrogen-free lyophilizate intended for intravenous administration. The IV administration of dexrazoxane is in acidic condition with HCl adjusting the pH.[1]
Uses
Dexrazoxane has been used to protect the heart against the cardiotoxic side effects of chemotherapeutic drugs such as anthracyclines,[2] such as daunorubicin or doxorubicin or other chemotherapeutic agents.[3] However, in July 2011 the US Food and Drug Administration released a statement restricting use only in adult patients with cancer who have received > 300 mg/m2 doxorubicin (an anthracycline) or > 540 mg/m2 epirubicin (another chemotherapeutic agent) and general approval for use for cardioprotection.[4][5] That showed a possibly higher rate of secondary malignancies and acute myelogenous leukemia in pediatric patients treated for different cancers with both dexrazoxane and other chemotherapeutic agents that are associated with secondary malignancies.[6]
The United States Food and Drug Administration has also approved a dexrazoxane hydrochloride drug, brand name Totect or Savene (developed by TopoTarget), for use as a treatment of extravasation resulting from IV anthracycline chemotherapy.[7][8] Extravasation is an adverse event in which chemotherapies containing anthracylines leak out of the blood vessel and necrotize the surrounding tissue.
Mechanism
As a derivative of EDTA, dexrazoxane chelates iron and thus reduces the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals.[9] The exact chelation mechanism is unknown, but it has been postulated that dexrazoxane can be converted into ring-opened form intracellularly and interfere with iron-mediated free radical generation that is in part thought to be responsible for anthryacycline induced cadiomyopathy.[10] It was speculated that dexrazoxane could be used for further investigation to synthesize new antimalarial drugs.[11]
References
- ↑ http://www.rxlist.com/zinecard-drug.htm
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Tebbi CK, et al. J Clin Oncol 2007; 25: 493–500
- ↑ Salzer WL, et al. Leukemia 2010; 24: 355–70
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Totect label on FDA's website
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ http://labeling.pfizer.com/ShowLabeling.aspx?id=514
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
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