AHFS/Drugs.com Monograph ATC code V03AF02 (WHO) PubChem CID 71384 Molar mass 268.269 g/mol | MedlinePlus a609010 CAS Number 24584-09-6 IUPHAR/BPS 7330 CAS ID 24584-09-6 | |
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Dexrazoxane hydrochloride (Zinecard by Pfizer in USA and Canada; Cardioxane by Clinigen Group 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.
Contents
Uses
Dexrazoxane has been used to protect the heart against the cardiotoxic side effects of chemotherapeutic drugs such as anthracyclines, such as daunorubicin or doxorubicin or other chemotherapeutic agents. 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. 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.
The United States Food and Drug Administration has also approved a dexrazoxane hydrochloride drug, brand names Totect and Savene (approved in the EU) marketed by Clinigen Group, for use as a treatment of extravasation resulting from IV anthracycline chemotherapy. 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. 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. It was speculated that dexrazoxane could be used for further investigation to synthesize new antimalarial drugs.