Dexrazoxane

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Dexrazoxane
Clinical data
AHFS/Drugs.comMonograph
MedlinePlusa609010
License data
Intravenous
ATC code
Legal status
Legal status
Identifiers
  • 4-[(2S)-2-(3,5-Dioxopiperazin-1-yl)propyl]piperazine-2,6-dione
JSmol)
  • O=C2NC(=O)CN(C[C@@H](N1CC(=O)NC(=O)C1)C)C2
  • InChI=1S/C11H16N4O4/c1-7(15-5-10(18)13-11(19)6-15)2-14-3-8(16)12-9(17)4-14/h7H,2-6H2,1H3,(H,12,16,17)(H,13,18,19)/t7-/m0/s1 checkY
  • Key:BMKDZUISNHGIBY-ZETCQYMHSA-N checkY
  (verify)

Dexrazoxane hydrochloride (Zinecard, Cardioxane) is a cardioprotective agent. It was discovered by Eugene Herman in 1972. The IV administration of dexrazoxane is in acidic condition with HCl adjusting the pH.[1]

Uses

Dexrazoxane has been used to protect 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 European Medicines Agency (EMA) released a statement restricting use only in adult patients with cancer who have received > 300 mg/m2 doxorubicin or > 540 mg/m2 epirubicin 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]
On July 19, 2017, based on evaluation of the currently available data the European Commission issued an EU-wide legally binding decision to implement the recommendations of the Committee for Medicinal Products for Human Use (CHMP) on dexrazoxane and lifted its 2011-contraindication for primary prevention of anthracycline-induced cardiotoxicity with dexrazoxane in children and adolescents where high doses (≥ 300 mg/m3) of anthracyclines are anticipated.

Dexrazoxane was designated by the US FDA as an orphan drug for "prevention of cardiomyopathy for children and adults 0 through 16 years of age treated with anthracyclines".[7] This decision allows virtually all children to receive dexrazoxane starting with the first dose of anthracycline at the discretion of the treating provider. The label change by the agency announcing dexrazoxane as an approved cardio-oncology protectant has been followed by a review by the agency.[8] Currently, the only FDA and EMA approved cardioprotective treatment for anthracycline cardioprotection is dexrazoxane, which provides effective primary cardioprotection against anthracycline-induced cardiotoxicity without reducing anthracycline activity and without enhancing secondary malignancies.[9]

The United States

necrotize
the surrounding tissue.

Mechanism

As a derivative of

chelates iron and thus reduces the number of metal ions complexed with anthracycline and, consequently, decrease the formation of superoxide radicals.[12] 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 cardiomyopathy.[13] It was speculated that dexrazoxane could be used for further investigation to synthesize new antimalarial drugs.[14]

References

  1. ^ "Zinecard (Dexrazoxane): Side Effects, Interactions, Warning, Dosage & Uses".
  2. PMID 15247354
    .
  3. S2CID 20119026
    .
  4. PMID 17290056
    .
  5. PMID 20016527
    .
  6. ^ "FDA Statement on Dexrazoxane". Food and Drug Administration. Archived by the Wayback Machine. 20 July 2011. Archived from the original on 18 August 2011. Retrieved 29 October 2023.
  7. ^ "Orphan drug designations and approvals". Retrieved June 7, 2019.
  8. ^ "Cardioxane". 2018-09-17.
  9. PMID 29747541
    .
  10. ^ "NDA 22-025 TOTECT™ (DEXRAZOXANE) FOR INJECTION | Totect™ Package Insert" (PDF). FDA. Archived by the Wayback Machine. Archived from the original (PDF) on 25 March 2009. Retrieved 29 October 2023.
  11. S2CID 7753443
    .
  12. S2CID 25950994
    .
  13. ^ "ZINECARD- dexrazoxane hydrochloride injection, powder, lyophilized, for solution". Pharmacia and Upjohn Company LLC.
  14. PMID 9990337
    .
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