The BEXXAR therapeutic regimen (Tositumomab and Iodine 131 Tositumomab) is an anti-neoplastic radioimmunotherapeutic monoclonal antibody-based regimen composed of the monoclonal antibody, Tositumomab, and the radiolabeled monoclonal antibody, Iodine 1131 Tositumomab.

Tositumomab is a murine lgG_2alambda monoclonal antibody directed agains t the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Tositumomab is produced in an antibiotic-free culture of mammalian cells and is composed of two murine gamma 2a heavy chains of 451 amino acids each and two lambda light chains of 220 amino acids each. The approximate molecular weight of Tositumomab is 150kD .

Tositumomab is supplied as a sterile, pyrogen-free, clear to opalescent, colorless to slightly yellow, preservative-free liquid concentrate. It is supplied at a nominal concentration of 14 mg/mL Tositumomab in 35 mg and 225 mg single-use vials. The formulation contains 10% (w/v) maltose, 145 mM sodium chloride, 10 mM phosphate, and Water for Injection, USP. The pH is approximately 7.2.

Iodine 131 Tositumomab is a radio-iodinated derivative of Tositumomab tha t has been covalently linked to lodine-131. Unbound radio-iodine and other reactants have been removed by chromatographic purification steps. Iodine 1131 Tositumomab is supplied as a sterile, clear, preservative-free liquid for IV administration. The dosimetric dosage form is supplied at nominal protein and activity concentrations of 0.1 mg/mL and 0.61 mCi/mL (at date of calibration), respectively. The therapeutic dosage form is supplied at nominal protein and activity concentrations of 1.1 mg/mL and 5.6 mCi/mL (at date of calibration), respectively. The formulation for the dosimetric and the therapeutic dosage forms contains 4.4%-6.6% (w/v) povidone, 1-2 mg/mL maltose (dosimetric dose) or 9-15 mg/mL maltose (therapeutic dose), 0.85-0.95 mg/mL sodium chloride, and 0.9-1.3 mg/mL ascorbic acid. The pH is approximately 7.0.

The BEXXAR therapeutic regimen is administered in two discrete steps: the dosimetric and therapeutic steps. Each step consists of a sequential infusion of Tositumomab followed by Iodine 131 Tositumomab. The therapeutic step is administered 7-14 days after the dosimetric step. The BEXXAR therapeutic regimen is supplied in two distinct package configurations as follows:

BEXXAR Dosimetric Packaging

†A carton containing two single-use 225 mg vials and one single-use 35 mg vial of Tositumomab supplied by McKesson BioServices and

†A package containing a single-use vial of Iodine 131 Tositumomab (0.61 mCi/mL at calibration), supplied by MDS Nordion.

BEXXAR Therapeutic Packaging

†A carton containing two single-use 225 mg vials and one single-use 35 mg vial of Tositumomab, supplied by McKesson BioServices and

†A package containing one or two single-use vials of Iodine 131 Tositumomab (5.6 mCi/mL at calibration), supplied by MDS Nordion.

Iodine-131 decays with beta and gamma emissions with a physical half-life of 8.04 days. The principal beta emission has a mean energy of 191.6 keV and the principal gamma emission has an energy of 364.5 keV (Ref 1).

The specific gamma ray constant for Iodine-131 is 2.2 R/millicurie hour at 1 cm. The first half-value layer is 0.24 cm lead (Pb) shielding. A range of values is shown in Table 1 for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb. To facilitate control of the radiation exposure from this radionuclide, the use of a 2.55 cm thickness of Pb will attenuate the radiation emitted by a factor of about 1,000.

The fraction of lodine-131 radioactivity that remains in the vial after the date of calibration is calculated as follows:

Fraction of remaining radioactivity of lodine-131 after x days = 2^-(x/8.04). Physical decay is presented in Table 2.

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