Dexrazoxane

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Dexrazoxane
Dexrazoxane.svg
Systematic (IUPAC) name
4-[(2S)-2-(3,5-dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a609010
Legal status
?
Identifiers
CAS number 24584-09-6 YesY
ATC code V03AF02
PubChem CID 71384
DrugBank DB00380
ChemSpider 64479 YesY
UNII 048L81261F YesY
KEGG D03730 YesY
ChEBI CHEBI:50223 YesY
ChEMBL CHEMBL1738 YesY
Chemical data
Formula C11H16N4O4 
Mol. mass 268.269 g/mol
 YesY (what is this?)  (verify)

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[edit]

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[edit]

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 be 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[edit]

  1. ^ http://www.rxlist.com/zinecard-drug.htm
  2. ^ Lipshultz, Steven E.; Rifai, Nader; Dalton, Virginia M.; Levy, Donna E.; Silverman, Lewis B.; Lipsitz, Stuart R.; Colan, Steven D.; Asselin, Barbara L. et al. (2004). "The Effect of Dexrazoxane on Myocardial Injury in Doxorubicin-Treated Children with Acute Lymphoblastic Leukemia". New England Journal of Medicine 351 (2): 145–53. doi:10.1056/NEJMoa035153. PMID 15247354. 
  3. ^ Bjelogrlic, Snezana K.; Radic, Jelena; Radulovic, Sinisa; Jokanovic, Milan; Jovic, Viktor (2007). "Effects of Dexrazoxane and Amifostine on Evolution of Doxorubicin Cardiomyopathy in Vivo". Experimental Biology and Medicine 232 (11): 1414–24. doi:10.3181/0705-RM-138. PMID 18040065. 
  4. ^ Tebbi CK, et al. J Clin Oncol 2007; 25: 493–500
  5. ^ Salzer WL, et al. Leukemia 2010; 24: 355–70
  6. ^ "FDA Statement on Dexrazoxane". 
  7. ^ Totect label on FDA's website
  8. ^ Kane, Robert C.; McGuinn, W. David; Dagher, Ramzi; Justice, Robert; Pazdur, Richard (2008). "Dexrazoxane (Totect™): FDA Review and Approval for the Treatment of Accidental Extravasation Following Intravenous Anthracycline Chemotherapy". The Oncologist 13 (4): 445–50. doi:10.1634/theoncologist.2007-0247. PMID 18448560. 
  9. ^ Jones, Robin L. (2008). "Utility of dexrazoxane for the reduction of anthracycline-induced cardiotoxicity". Expert Review of Cardiovascular Therapy 6 (10): 1311–7. doi:10.1586/14779072.6.10.1311. PMID 19018683. 
  10. ^ http://labeling.pfizer.com/ShowLabeling.aspx?id=514
  11. ^ Loyevsky, Mark; Sacci, John B.; Boehme, Patricia; Weglicki, William; John, Christy; Gordeuk, Victor R. (1999). "Plasmodium falciparum and Plasmodium yoelii: Effect of the Iron Chelation Prodrug Dexrazoxane on in Vitro Cultures". Experimental Parasitology 91 (2): 105–14. doi:10.1006/expr.1998.4371. PMID 9990337.