The Zevalin^® (Ibritumomab Tiuxetan) therapeutic regimen can be completed over the course of 7 to 9 days in an outpatient setting. The Zevalin therapeutic regimen consists of 3 components: Rituximab, In-111 Zevalin (imaging dose), and Y-90 Zevalin (therapeutic dose).

A typical course of treatment begins on day 1 with an IV infusion of Rituximab 250 mg/m², which may take several hours to complete. Within 4 hours of completing the Rituximab infusion, In-111 Zevalin 5.0 mCi is delivered by a 10-minute IV infusion. Whole body gamma camera images are required 48 to 72 hours following the infusion of In-111 Zevalin. To resolve ambiguities, optional images at other timepoints may be necessary. Provided the images confirm no altered biodistribution, on day 7, 8, or 9 a second IV infusion of Rituximab 250 mg/m², which may take several hours to complete, is administered. Within 4 hours of completing the second Rituximab infusion, the therapeutic dose of Y-90 Zevalin is dosed by a 10-minute IV infusion. The dose of
Y-90 Zevalin is based on the patient's baseline platelet count and actual body weight^[1]. Y-90 Zevalin should not be administered to patients with altered biodistribution as determined by imaging with In-111 Zevalin.

The biodistribution of In-111 Zevalin should be assessed by a visual evaluation of whole body planar view anterior and posterior gamma images. A set of images at 48-72 hours after injection is required. To resolve ambiguities, optional images at other timepoints may be necessary.

Download the Patient Treatment Timeline and Appointment Schedule as a PDF

Important dosing information
Y-90 Zevalin is dosed at 0.4 mCi/kg (14.8 MBq/kg) actual body weight for patients with platelet counts ≥150,000/mm³ and at 0.3 mCi/kg (11.1 MBq/kg) actual body weight for patients with platelet counts of 100,000-149,000/mm³. The prescribed, measured, and administered dose of Y-90 Zevalin must not exceed the absolute maximum allowable dose of 32.0 mCi (1184 MBq), regardless of the patient's body weight. Do not give Y-90 Zevalin to patients with platelet counts <100,000/mm³.

In-111 Zevalin and Y-90 Zevalin should not be used in the absence of the Rituximab predose^[1]. NOTE THAT THE DOSE OF RITUXIMAB IS LOWER WHEN USED AS PART OF THE ZEVALIN THERAPEUTIC REGIMEN, AS COMPARED TO THE DOSE OF RITUXIMAB WHEN USED AS A SINGLE AGENT. DO NOT ADMINISTER RITUXIMAB AS AN INTRAVENOUS PUSH OR BOLUS. Hypersensitivity reactions may occur. Premedication, consisting of acetaminophen and diphenhydramine, should be considered before each infusion of Rituximab. Because the Zevalin therapeutic regimen includes the use of Rituximab, please see the full prescribing information for Rituximab.

Infusion procedure for radiolabeled Zevalin
Radiolabeled Zevalin must be administered within 4 hours of completion of the Rituximab infusion. The patient will receive radiolabeled Zevalin at a nuclear medicine or radiation oncology facility. Both In-111 Zevalin and Y-90 Zevalin are administered by an IV infusion given over 10 minutes. In-111 Zevalin and
Y-90 Zevalin should not be used in the absence of the Rituximab predose^[1].

Why Rituximab is given prior to administration of In-111 ZEVALIN and
Y-90 Zevalin
Rituximab is given prior to administration of In-111 Zevalin and Y-90 Zevalin to deplete circulating B-cells.

Dosimetry is not required when dosing Y-90 Zevalin
Dosimetry is not required for patients with relapsed or refractory low-grade, follicular, or transformed B-cell NHL. Data from clinical studies have confirmed that Y-90 Zevalin dosing based on pretreatment platelet count and actual patient body weight results is safe and effective therapy.

Y-90 Zevalin is dosed on the basis of patient weight and platelet count because the tiuxetan chelator leads to a stable bond between isotope and antibody, because the isotope has a short half-life, and because the urinary excretion over 7 days was a median of 7.2% of initial injected activity. In addition, clinical studies did not demonstrate a correlation between hematologic toxicity in patients and dosimetric parameters^[2][3].

Precautions for hypersensitivity reactions
Anaphylactic and other hypersensitivity reactions have been reported following the intravenous administration of proteins to patients. Medications for the treatment of hypersensitivity reactions, e.g., epinephrine, antihistamines, and corticosteroids, should be available for immediate use in the event of an allergic reaction during administration of the Zevalin therapeutic regimen. Patients who have received murine proteins should be screened for human antimouse antibodies (HAMA). Patients with evidence of HAMA have not been studied and may be at increased risk of allergic or serious hypersensitivity reactions during treatment with the Zevalin therapeutic regimen^[1].

Recommended shielding
Other than the use of plastic or acrylic shielding, no special shielding is necessary. In order to avoid production of bremsstrahlung energy, lead shielding should not be used^[8]. Appropriate shielding should, however, be used during radiolabeling.