TOTECT SIDE EFFECTS

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

Table 2 summarizes laboratory abnormalities from studies 1 and 2.

Table 2: Laboratory Abnormalities

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