In Brief: Dexrazoxane for Anthracycline Extravasation

The FDA has approved a new formulation of dexrazoxane (Totect) for treatment of extravasation from intravenous (IV) anthracyclines such as doxorubicin (Adriamycin, and others). Dexrazoxane has been available since 1995 as Zinecard for protection against the cardiac toxicity of anthracyclines (Med Lett Drugs Ther 1995; 37:110). It is also available generically. The drug’s precise mechanism of action is not known, but anthracyclines are vesicants that bind to DNA and act as oxidizing agents in the presence of iron. Dexrazoxane is a topoisomerase inhibitor, possibly interfering with anthracycline effects on DNA, and is also a potent iron-chelating agent, preventing free-radical formation. In uncontrolled clinical trials, dexrazoxane appears to have prevented severe necrosis that would require surgical debridement (HT Mouridsen et al. Ann Oncol 2007; 18:546. epub). It is given in a dose of 1000 mg/m² (2000 mg maximum) as an IV infusion over 1-2 hours as soon as possible (no later than 6 hours) after extravasation has occurred and again 24 hours later, and then in a dose of 500 mg/m² (1000 mg maximum) 48 hours after the first dose. The dose should be reduced by half in patients with a creatinine clearance <40 mL/min.

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