Totect

Safety

ADVERSE REACTIONS

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
Combined
(All causalities)
% (N=80)
Total number of patients with at least one event 85
General disorders and administration site conditions
Pyrexia
Injection site pain/injection site discomfort
Fatigue
Edema peripheral
Injection site phlebitis
58
21
16
13
10
6
Gastrointestinal disorders
Nausea
Vomiting
Diarrhea
Abdominal pain
Constipation
55
43
19
11
6
6
Infections and infestations
Postoperative infection
30
16
Nervous system disorders
Dizziness
Headache
24
11
6
Skin and subcutaneous disorders
Alopecia
18
14
Respiratory, thoracic and mediastinal disorders
Dyspnea
Pneumonia
Cough
16
8
6
5
Vascular disorders 15
Blood and lymphatic system disorders
Anemia
14
6
Psychiatric disorders
Depression
Insomnia
14
8
5
Musculoskeletal and connective tissue disorders 13
Metabolism and nutrition disorders
Anorexia
10
5
Cardiac disorders 5

Table 2 summarizes laboratory abnormalities from studies 1 and 2.

Table 2: Laboratory Abnormalities
Laboratory Abnormality Grade
3
%
Grade
4
%
Grade
2 to 4
%
Hematologic:
Decreased hemoglobin 3 0 43
Decreased WBC 25 20 73
Decreased neutrophils 22 24 61
Decreased platelets 21 0 26
Hepatic:
Increased bilirubin 2 0 11
Increased AST 1 1 28
Increased ALT 1 5 22
Increased alkaline phosphatase 0 0 4
Increased LDH 0 0 5
Metabolic:
Increased creatinine 2 2 14
Decreased sodium 5 1 6
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
CONTRAINDICATIONS

None.

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.

DRUG INTERACTIONS
TOTECT is not recommended for use with dimethyl sulfoxide (DMSO).

ADVERSE REACTIONS
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.

Click here to view Full Prescribing Information