FDA Approval for Dexrazoxane Hydrochloride
Brand name(s): Zinecard®, Totect™
- Approved for treatment of extravasation caused by intravenous anthracycline chemotherapy (Totect)
- Approved for treatment of cardiomyopathy caused by doxorubicin (Zinecard)
On September 6, 2007, the FDA approved dexrazoxane hydrochloride for injection (Totect™ made by TopoTarget USA, Inc.), equivalent to 500 mg dexrazoxane, for the treatment of extravasation resulting from intravenous anthracycline chemotherapy. Extravasion occurs when injected drugs leak out of the vein and into the skin.
In two studies, patients who were receiving single-agent anthracycline intravenously (usually as part of combination chemotherapy) and who developed extravasation symptoms of pain, burning, swelling, and redness near the infusion site received dexrazoxane hydrochloride to reduce surgical interventions for tissue injury following anthracycline extravasation. The protocol required extravasation to be confirmed by the presence of fluorescence in tissue biopsies.
The first dexrazoxane hydrochloride dose was given as soon as possible and within six hours following extravasation. After the first dose, treatment was repeated 24 and 48 hours later for a total of three doses. Dexrazoxane hydrochloride was administered as a 1-2 hour IV infusion through a different venous access location. The first and second doses were 1000 mg/m2 and the third dose was 500 mg/m2 up to a maximum daily dose of 2000 mg on days 1 and 2 and 1000 mg on the third day.
Extravasation was confirmed in 57 patients. The anthracyclines most commonly involved were epirubicin (56 percent) and doxorubicin (41 percent). Peripheral sites of extravasation included the forearm in 63 percent, the hand in 21 percent, and the antecubital area in 11 percent; four patients received the anthracycline via a central venous access device (CVAD). Most patients presented with swelling (83 percent), redness (78 percent), and pain (43 percent).
After dexrazoxane hydrochloride treatment, only one of the 57 patients required surgery. Thirteen patients had late adverse effects at the injection site such as pain, fibrosis, atrophy, and local sensory disturbance; all were judged as mild except in the one patient who required surgery. None of the four patients with CVADs required surgical intervention.
Dexrazoxane hydrochloride is a cytotoxic drug. When administered to patients receiving anthracycline-containing cytotoxic therapy, additive cytotoxicity may occur. Treatment with dexrazoxane hydrochloride is associated with leukopenia, neutropenia, and thrombocytopenia. Reversible elevations of liver enzymes may occur. Renal excretion is the primary metabolic pathway. Dimethylsulfoxide (DMSO) should not be used in patients who are receiving dexrazoxane to treat anthracycline-induced extravasation.
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In May 1995, the U.S. Food and Drug Administration (FDA) approved dexrazoxane hydrochloride for injection (Zinecard®, made by Pfizer U.S. Pharmaceuticals) as a treatment to reduce the incidence and severity of cardiomyopathy associated with doxorubicin administration in certain breast cancer patients.
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This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Understanding the Approval Process for New Cancer Treatments.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.