Manufacturer: TopoTarget A/S, Copenhagen, Denmark
Indication: Totect is used to treat extravasation resulting from IV anthracycline agents used in chemotherapy. Anthra-cyclines (e.g., daunorubicin, doxorubicin, and epirubicin) constitute one of the cornerstones in the treatment of breast cancer and leukemia. Extravasation occurs when injected drugs leak out of the vein and into the skin.
Drug Class: The formula for dexrazoxane is (S)-4,4′-(1-methyl-1,2-ethanediyl)bis-2,6-piperazinedione. A potent intra-cellular chelating agent, it is a derivative of ethylenediamine tetraacetic acid (EDTA). Apcalis Oral Jelly
Uniqueness of Drug: A metal ion chelator, dexrazoxane is also a catalytic inhibitor of DNA topoisomerase II. However, the mechanism of action that protects against the extravasation of anthracycline is not known. Topoisomerase enzymes are essential for cell growth and proliferation, and they are the target of a group of anticancer chemotherapeutics (the anthracyclines). Totect blocks the activity of the topo-isomerase enzyme and prevents the effect of anthracyclines.
Pregnancy Category D. Dexrazoxane was toxic to pregnant rats at doses of 2 mg/kg (one-eightieth of the human dose defined in milligrams per square meter [mg/m2]) and embry-otoxic and teratogenic at a dose of 8 mg/kg (about half the human dose on a mg/m2 basis) when given daily during the period of organogenesis. Teratogenic effects in the rat included an imperforate anus, microphthalmia, and anophthalmia.
In offspring that developed to maturity, fertility was impaired in male and female rats treated in utero during organogenesis at a dose of 8 mg/kg. In rabbits, a dose of 5 mg/kg daily (about one-sixteenth of the human dose on a mg/m2 basis) during the period of organogenesis caused maternal tox-icity and a dose of 20 mg/kg (one-fourth the human dose on a mg/m2 basis) was embryotoxic and teratogenic. Terato-genic effects in the rabbit included several skeletal malformations such as a short tail, rib and thoracic malformations, and soft-tissue variations as well as agenesis of the gallbladder and of the intermediate lobe of the lung.
Table 2 Dosage for Dexrazoxane (Totect)
Recommended Dose Recommended Dose
Day one: 1,000 mg/m2 2,000 mg
Day two: 1,000 mg/m2 2,000 mg
Day three: 500 mg/m2 1,000 mg
There is no adequate information about the use of Totect in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus.
Precautions: Dexrazoxane HCl is cytotoxic. When givento patients receiving anthracycline-containing cytotoxic therapy, additional cytotoxicity may occur. Totect is associated with leukopenia, neutropenia, and thrombocytopenia. Hematological monitoring should be performed. Reversible elevations of liver enzymes may occur with dexrazoxane.
Greater exposure to dexrazoxane may occur in patients with compromised renal function. Blood counts and liver enzymes should be monitored.
Dosage and Administration: Totect should be given once daily for three consecutive days (Table 2). The first infusion should be initiated as soon as possible and within the first six hours after extravasation. The dose should be reduced by 50% in patients with creatinine clearance values below 40 mL/ minute.
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Commentary: Totect received orphan drug status. This is the only approved drug for the treatment of extravasation resulting from IV anthracycline chemotherapy. It is used as therapy when IV anthracycline accidentally leaks into the surrounding healthy tissue.