itive for HAMA in an ELISA assay that detects antibodies to the Fc portion of IgG1 murine immunoglobulin and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of HAMA in patients treated with the BEXXAR therapeutic regimen with the incidence of HAMA in patients treated with other products may be misleading.
OVERDOSAGE
The maximum dose of the BEXXAR therapeutic regimen that was administered in clinical trials was 88 cGy. Three patients were treated with a total body dose of 85 cGy of Iodine I 131 Tositumomab in a dose escalation study. Two of the 3 patients developed Grade 4 toxicity of 5 weeks duration with subsequent recovery. In addition, accidental overdose of the BEXXAR therapeutic regimen occurred in one patient at a total body dose of 88 cGy. The patient developed Grade 3 hematologic toxicity of 18 days duration. Patients who receive an accidental overdose of Iodine I 131 Tositumomab should be monitored closely for cytopenias and radiation-related toxicity. The effectiveness of hematopoietic stem cell transplantation as a supportive care measure for marrow injury has not been studied; however, the timing of such support should take into account the pharmacokinetics of the BEXXAR therapeutic regimen and decay rate of the Iodine-131 in order to minimize the possibility of irradiation of infused hematopoietic stem cells.
DOSAGE AND ADMINISTRATION
Recommended Dose
The BEXXAR therapeutic regimen consists of four components administered in two discrete steps: the dosimetric step, followed 7-14 days later by a therapeutic step.
Note: The safety of the BEXXAR therapeutic regimen was established only in the setting of patients receiving thyroid blocking agents and premedication to ameliorate/prevent infusion reactions (see Concomitant Medications).
Dosimetric step
Tositumomab 450 mg intravenously in 50 ml 0.9% Sodium Chloride over 60 minutes. Reduce the rate of infusion by 50% for mild to moderate infusional toxicity; interrupt infusion for severe infusional toxicity. After complete resolution of severe infusional toxicity, infusion may be resumed with a 50% reduction in the rate of infusion.
Iodine I 131 Tositumomab (containing 5.0 mCi Iodine-131 and 35 mg Tositumomab) intravenously in 30 ml 0.9% Sodium Chloride over 20 minutes. Reduce the rate of infusion by 50% for mild to moderate infusional toxicity; interrupt infusion for severe infusional toxicity. After complete resolution of severe infusional toxicity, infusion may be resumed with a 50% reduction in the rate of infusion.
Therapeutic step
Note: Do not administer the therapeutic step if biodistribution is altered (see Assessment of Biodistribution of Iodine I 131 Tositumomab).
Tositumomab 450 mg intravenously in 50 ml 0.9% Sodium Chloride over 60 minutes. Reduce the rate of infusion by 50% for mild to moderate infusional toxicity; interrupt infusion for severe infusional toxicity. After complete resolution of severe infusional toxicity, infusion may be resumed with a 50% reduction in the rate of infusion.
Iodine I 131 Tositumomab (see CALCULATION OF IODINE-131 ACTIVITY FOR THE THERAPEUTIC DOSE). Reduce the rate of infusion by 50% for mild to moderate infusional toxicity; interrupt infusion for sever
