ADVERSE REACTIONS
Overview
Dexrazoxane has been studied previously as a cytotoxic agent. Adverse reactions of nausea/vomiting, diarrhea, stomatitis, bone marrow suppression (neutropenia, thrombocytopenia), altered liver function (increased AST/ALT), and infusion site burning have been observed. These adverse reactions have been reversible.
Discussion of Adverse Reaction Information
Because clinical trials are conducted under varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.
In the two 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 chemotherapy. The adverse reaction data reflect exposure to Totect™ 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 reaction occurring with ≥ 5% frequency.
Table 1 Adverse Reactions Occurring at ≥ 5% Frequency | MedDRA System Organ Class (SOC) and Preferred term | Study 1 and 2
Combined
(All causalities)
N=80 (%) |
| Total number of patients with at least one event | 68 (85) |
General disorders and
administration site conditions | 46 (58) |
| Pyrexia | 17 (21) |
| Injection site pain | 13 (16) |
| Fatigue | 10 (13) |
| Edema peripheral | 8 (10) |
| Injection site phlebitis | 5 (6) |
| Gastrointestinal disorders | 44 (55) |
| Nausea | 34 (43) |
| Vomiting | 15 (19) |
| Diarrhea | 9 (11) |
| Abdominal pain | 5 (6) |
| Constipation | 5 (6) |
| Infections and infestations | 24 (30) |
| Postoperative infection | 13 (16) |
| Nervous system disorders | 19 (24) |
| Dizziness | 9 (11) |
| Headache | 5 (6) |
| Skin and subcutaneous disorders | 14 (18) |
| Alopecia | 11 (14) |
| Respiratory, thoracic and mediastinal disorders | 13 (16) |
| Dyspnea | 6 (8) |
| Pneumonia | 5 (6) |
| Cough | 4 (5) |
| Vascular disorders | 12 (15) |
| Blood and lymphatic system disorders | 11 (14) |
| Anemia | 5 (6) |
| Psychiatric disorders | 11 (14) |
| Depression | 6 (8) |
| Insomnia | 4 (5) |
| Musculoskeletal and connective tissue disorders | 10 (13) |
| Metabolism and nutrition disorders | 8 (10) |
| Anorexia | 4 (5) |
| Cardiac disorders | 4 (5) |
Neutropenia and febrile neutropenia each occurred in 2.5% of patients.
Table 2 summarizes laboratory adverse reactions from studies 1 and 2 combined.
Table2: Laboratory Adverse Reactions CTCAE version 3
Term | CTC grade
3 | CTC grade
4 | CTC grade
2 to 4 |
| N (%) | N (%) | N (%) |
| Hematologic: | |
| Decreased hemoglobin | 2 (3) | 0 | 34 (43) |
| Decreased WBC | 20 (25) | 16 (20) | 58 (73) |
| Decreased neutrophils | 17 (22) | 19 (24) | 48 (61) |
| Decreased platelets | 17 (21) | 0 | 21 (26) |
| Hepatic: | |
| Increased bilirubin | 1 (2) | 0 | 6 (11) |
| Increased AST | 1 (1) | 1 (1) | 21 (28) |
| Increased ALT | 1 (1) | 4 (5) | 17 (22) |
| Increased alkaline phosphatase | 0 | 0 | 3 (4) |
| Increased LDH | 0 | 0 | 1 (5) |
| Metabolic: | |
| Increased creatinine | 1 (2) | 1 (2) | 8 (14) |
| Decreased sodium | 4 (5) | 1 (1) | 5 (6) |
| Increased calcium total | 1 (2) | 1 (2) | 4 (7) |
|
