|Trade names||Zinecard, Cardioxane, others|
|Other names||Dexrazoxane hydrochloride|
|Main uses||Prevent cardiomyopathy due to doxorubicin, extravasation of anthracyclines|
|Side effects||Pain at site of injection|
|Chemical and physical data|
|Molar mass||268.273 g·mol−1|
|3D model (JSmol)|
Dexrazoxane, sold under the brand name Zinecard among others, is a medication used to prevent cardiomyopathy due to doxorubicin and in extravasation of anthracyclines. It is given by injection into a vein.
Common side effects include pain at the site of injection, nausea, and diarrhea. Other side effects may include bone marrow suppression. In children in may increase the risk of further cancers. It is an antidote to anthracyclines.
Dexrazoxane was discovered in 1972. It was approved for medical use in the United States in 1995 and Europe in 2006. In the United States 500 mg costs about 420 USD as of 2021. This amount in the United Kingdom is about £160.
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 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. 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. In 2017, based on evaluation of the data the European Commission issued an EU-wide 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". This decision allows 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. As of 2018 it is 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.
For prevention of heart toxicity 10 mg/m2 of dexrazoxane is given for every 1 mg/m2 of doxorubicin that is planned to be used.
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 cardiomyopathy. It was speculated that dexrazoxane could be used for further investigation to synthesize new antimalarial drugs.
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