Zevalin (Ibritumomab Tiuxetan) - Description

DESCRIPTION

ZEVALIN®

ZEVALIN (Ibritumomab Tiuxetan) is the immunoconjugate resulting from a stable thiourea covalent bond between the monoclonal antibody Ibritumomab and the linker-chelator tiuxetan [N-[2-bis(carboxymethyl)amino]-3-(p-isothiocyanatophenyl)-propyl] -[N-[2-bis(carboxymethyl)amino]-2-(methyl)-ethyl]glycine. This linker-chelator provides a high affinity, conformationally restricted chelation site for Indium-111 or Yttrium-90. The approximate molecular weight of Ibritumomab Tiuxetan is 148 kD.

The antibody moiety of ZEVALIN is Ibritumomab, a murine IgG₁ kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Ibritumomab is produced in Chinese hamster ovary cells and is composed of two murine gamma 1 heavy chains of 445 amino acids each and two kappa light chains of 213 amino acids each.

ZEVALIN THERAPEUTIC REGIMEN

The ZEVALIN therapeutic regimen is administered in two steps: Step 1 includes one infusion of Rituximab preceding In-111 ZEVALIN. Step 2 follows Step 1 by seven to nine days and consists of a second infusion of Rituximab followed by Y-90 ZEVALIN.

ZEVALIN is supplied as two separate and distinctly labeled kits that contain all of the non-radioactive ingredients necessary to produce a single dose of In-111 ZEVALIN and a single dose of Y-90 ZEVALIN, both essential components of the ZEVALIN therapeutic regimen. Indium-111 chloride and Rituximab must be ordered separately from the ZEVALIN kit. Yttrium-90 Chloride Sterile Solution is supplied by MDS Nordion when the Y-90 ZEVALIN kit is ordered.

ZEVALIN KITS

Each of the two ZEVALIN kits contains four vials that are used to produce a single dose of either In-111 ZEVALIN or Y-90 ZEVALIN, as indicated on the outer container label:

1. One (1) ZEVALIN vial containing 3.2 mg of Ibritumomab Tiuxetan in 2 mL of 0.9% sodium chloride solution; a sterile, pyrogen-free, clear, colorless solution that may contain translucent particles; no preservative present.
2. One (1) 50 mM Sodium Acetate Vial containing 13.6 mg of sodium acetate trihydrate in 2 mL of Water for Injection; a sterile, pyrogen-free, clear, colorless solution; no preservative present.
3. One (1) Formulation Buffer Vial containing 750 mg of Albumin (Human), 76 mg of sodium chloride, 21 mg of sodium phosphate dibasic heptahydrate, 4 mg of pentetic acid, 2 mg of potassium phosphate monobasic and 2 mg of potassium chloride in 10 mL of Water for Injection adjusted to pH 7.1 with either sodium hydroxide or hydrochloric acid; a sterile, pyrogen-free, clear yellow to amber colored solution; no preservative present.
4. One (1) empty Reaction Vial, sterile, pyrogen-free.

PHYSICAL/RADIOCHEMICAL CHARACTERISTICS OF IN-111

Indium-111 decays by electron capture, with a physical half-life of 67.3 hours (2.81 days) ^[1]. The product of radioactive decay is nonradioactive cadmium-111. Radiation emission data for In-111 are summarized in Table 1.

EXTERNAL RADIATION

The exposure rate constant for 37 MBq (1 mCi) of In-111 is 8.3 × 10^-4 C/kg/hr (3.2 R/hr) at 1 cm. Adequate shielding should be used with this gamma-emitter, in accordance with institutional good radiation safety practices.

To allow correction for physical decay of In-111, the fractions that remain at selected intervals before and after the time of calibration are shown in Table 2.

PHYSICAL/RADIOCHEMICAL CHARACTERISTICS OF Y-90

Yttrium-90 decays by emission of beta particles, with a physical half-life of 64.1 hours (2.67 days) ^[1]. The product of radioactive decay is non-radioactive zirconium-90. The range of beta particles in soft tissue ([khgr ]₉₀) is 5 mm. Radiation emission data for Y-90 are summarized in Table 3.

EXTERNAL RADIATION

The exposure rate for 37 MBq (1 mCi) of Y-90 is 8.3 × 10^-3 C/kg/hr (32 R/hr) at the mouth of an open Y-90 vial. Adequate shielding should be used with this beta-emitter, in accordance with institutional good radiation safety practices.

To allow correction for physical decay of Y-90, the fractions that remain at selected intervals before and after the time of calibration are shown in Table 4.