PHARMACOLOGIC CLASS: Topoisomerase II inhibitor/chelating agent
ACTIVE INGREDIENT: Dexrazoxane 500mg; per vial; pwd for IV infusion after reconstitution and dilution; preservative-free.
INDICATION: To treat extravasation resulting from IV anthracycline chemotherapy.
PHARMACOLOGY: The mechanism by which dexrazoxane diminishes tissue damage resulting from the extravasation of anthracycline drugs is unknown. Some evidence suggests that dexrazoxane inhibits topoisomerase II reversibly. Dexrazoxane is also converted intracellularly to a chelating agent that interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-mediated oxidative injury.
CLINICAL TRIALS: The efficacy of Totect in reducing tissue injury following anthracycline extravasation was studied in two, open-label, single arm, multicenter studies. In these two studies, patients were receiving single-agent anthracycline intravenously and developed extravasation symptoms near the infusion site. In total, 80 patients were enrolled and 57 were evaluable. The anthracyclines most commonly associated with extravasation were epirubicin and doxorubicin. Peripheral IV sites of extravasation included the forearm, hand, and the antecubital area; four patients received the anthracycline via a central venous access device (CVAD). Treatment with Totect was started as soon as possible and no later than 6 hours after extravasation with retreatment 24–48 hours later (a total of 3 doses). Totect was administered as 1–2 hour IV infusions through a different venous access location. The first and second doses were 1000mg/m2 and the third dose was 500mg/m2. In study 1, none of the 19 evaluable patients required surgical intervention and none had serious late sequelae. In study 2, one of the 38 evaluable patients required surgery. One additional non-evaluable patient required surgery for tissue necrosis. Thirteen patients had late sequelae at the event site such as site pain, fibrosis, atrophy, and local sensory disturbances; all were judged as mild except in the one patient who required surgery. None of the 4 patients with CVADs required surgical intervention.
ADULTS: Give once daily for 3 consecutive days by IV infusion over 1–2 hours. Initiate first dose as soon as possible and within first 6 hours after extravasation. Days 1 and 2: 1000mg/m2; max 2000mg. Day 3: 500mg/m2; max 1000mg. Renal impairment (CrCl <40mL/min): reduce dose by 50%.
CHILDREN: Not recommended.
PRECAUTIONS: Renal or hepatic impairment (monitor liver enzymes). Monitor for myelosuppression; obtain blood counts periodically. Elderly. Labor & delivery. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.
INTERACTIONS: Avoid dimethylsulfoxide (DMSO). Caution with concurrent cytotoxic agents (additive cytotoxicity).
ADVERSE REACTIONS: Inj site reactions, GI upset, stomatitis, leukopenia, neutropenia, thrombocytopenia, elevated liver enzymes, pyrexia, infections.
HOW SUPPLIED: Single-use vials—10 (w. diluent)
For more information call (866) 914-2922 or visit www.Totect.com