TOTECT SIDE EFFECTS

  • Generic Name: dexrazoxane for injection, intravenous infusion only
  • Brand Name: Totect
  • Drug Class: Cardioprotectant Agents
Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

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.

Extravasation

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 58
Pyrexia 21
Injection site pain/injection site discomfort 16
Fatigue 13
Edema peripheral 10
Injection site phlebitis 6
Gastrointestinal disorders 55
Nausea 43
Vomiting 19
Diarrhea 11
Abdominal pain 6
Constipation 6
Infections and infestations 30
Postoperative infection 16
Nervous system disorders 24
Dizziness 11
Headache 6
Skin and subcutaneous disorders 18
Alopecia 14
Respiratory, thoracic and mediastinal disorders 16
Dyspnea 8
Pneumonia 6
Cough 5
Vascular disorders 15
Blood and lymphatic system disorders 14
Anemia 6
Psychiatric disorders 14
Depression 8
Insomnia 5
Musculoskeletal and connective tissue disorders 13
Metabolism and nutrition disorders 10
Anorexia 5
Cardiac disorders 5

 

Table 2 summarizes laboratory abnormalities from studies 1 and 2.

Table 2: Laboratory Abnormalities

Laboratory Abnormality Grade 3 % Grade 40 % 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

 

Cardiomyopathy

The adverse reaction profile described in this section was identified from randomized, placebo-controlled, double-blind studies in patients with metastatic breast cancer who received the combination of the fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy regimen with or without dexrazoxane. The dose of doxorubicin was 50 mg/m² in each of these trials. Treatment was administered every three weeks until disease progression or cardiac toxicity.

Patients in clinical trials who received FAC with dexrazoxane experienced more severe leukopenia, granulocytopenia, and thrombocytopenia than patients receiving FAC without dexrazoxane.

Table 3 below lists the incidence of adverse reactions for patients receiving FAC with either dexrazoxane or placebo in the breast cancer studies. Adverse experiences occurring during courses 1 through 6 are displayed for patients receiving dexrazoxane or placebo with FAC beginning with their first course of therapy (columns 1 and 3, respectively). Adverse experiences occurring at course 7 and beyond for patients who received placebo with FAC during the first six courses and who then received either dexrazoxane or placebo with FAC are also displayed (columns 2 and 4, respectively).

The adverse reactions listed below in Table 3 demonstrate that the frequency of adverse reaction “Pain on Injection” has been greater for dexrazoxane arm, as compared to placebo.

Table 3: Adverse Reactions for Patients Receiving FAC with either Dexrazoxane or Placebo

Adverse Reaction Percentage (%) of Breast Cancer Patients With Adverse Reaction
FAC + Dexrazoxane FAC +Placebo
Courses 1 -6
N = 413
Courses ≥ 7
N = 102
Courses 1-6
N = 458
Courses ≥ 7
N = 99
Alopecia 94 100 97 98
Nausea 77 51 84 60
Vomiting 59 42 72 49
Fatigue/Malaise 61 48 58 55
Anorexia 42 27 47 38
Stomatitis 34 26 41 28
Fever 34 22 29 18
Infection 23 19 18 21
Diarrhea 21 14 24 7
Pain on injection 12 13 3 0
Sepsis 17 12 14 9
Neurotoxicity 17 10 13 5
Streaking/Erythema 5 4 4 2
Phlebitis 6 3 3 5
Esophagitis 6 3 7 4
Dysphagia 8 0 10 5
Hemorrhage 2 3 2 1
Extravasation 1 3 1 2
Urticaria 2 2 2 0
Recall Skin Reaction 1 1 2 0

 

SRC: NLM .