Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.
In the clinical studies, Totect was administered to patients also receiving chemotherapeutic agents for cancer, and the adverse reaction profile and laboratory abnormalities presented in Tables 1 and 2 reflect the combination of Totect, underlying disease, and already administered chemotherapy. The adverse reaction data reflect exposure to Totect from two clinical studies in 80 patients who received the first dose, 72 patients who received two doses, and 69 patients who received all three doses. Table 1 summarizes adverse reactions occurring with ≥ 5% frequency.
|Table 1 Adverse Reactions Occurring at ≥ 5% Frequency|
|System Organ Class (SOC) and Adverse Reaction||Study 1 and 2
|Total number of patients with at least one event||85|
|General disorders and administration site conditions
Injection site pain/injection site discomfort
Injection site phlebitis
|Infections and infestations
|Nervous system disorders
|Skin and subcutaneous disorders
|Respiratory, thoracic and mediastinal disorders
|Blood and lymphatic system disorders
|Musculoskeletal and connective tissue disorders||13|
|Metabolism and nutrition disorders
Table 2 summarizes laboratory abnormalities from studies 1 and 2.
|Table 2: Laboratory Abnormalities|
2 to 4
|Increased alkaline phosphatase||0||0||4|
|Increased calcium total||2||2||7|
INDICATION: TOTECT® (dexrazoxane) is indicated for the treatment of extravasation resulting from intravenous anthracycline chemotherapy.
IMPORTANT DOSAGE AND ADMINISTRATION INSTRUCTIONS
Vial contents must be reconstituted and diluted with 50 mL of 0.167 M sodium lactate injection solution and further mixed and diluted with the recommended dose in 1000 mL 0.9% Sodium Chloride before use. The TOTECT dose should be reduced by 50% in patients with creatinine clearance values < 40 mL/min.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Myelosuppression: TOTECT is associated with leukopenia, neutropenia, and thrombocytopenia. Perform hematological monitoring during treatment with TOTECT and cytotoxic chemotherapy as the myelosuppression and cytotoxic potential may be additive to that of chemotherapy alone.
Anaphylactic/Hypersensitivity Reactions: Hypersensitivity reactions including anaphylactic reaction, angioedema, skin reactions, bronchospasm, respiratory distress, hypotension and loss of consciousness have occurred in patients treated with dexrazoxane products and anthracyclines. Previous history of allergy to dexrazoxane products should be carefully considered prior to administration. Consider permanent discontinuation in patients with severe hypersensitivity reactions.
Embryo-Fetal Toxicity: TOTECT can cause fetal harm when administered to a pregnant woman. Advise patients of potential risk and to use effective contraception during treatment and 6 months following the last dose of TOTECT. Use in patients with hepatic impairment is not recommended.
TOTECT is not recommended for use with dimethyl sulfoxide (DMSO).
In the clinical studies, TOTECT was administered to patients also receiving chemotherapeutic agents for cancer, and the adverse reaction profile reflects the combination of TOTECT, underlying disease, and already administered chemotherapy. The most common adverse reactions (≥15%) are nausea, fever, injection site pain, vomiting, and postoperative infection.
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