Overview
11 DESCRIPTION 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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ibritumomab tiuxetan binds specifically to the CD20 antigen (human B-lymphocyte-restricted differentiation antigen, Bp35). The apparent affinity (K D ) of ibritumomab tiuxetan for the CD20 antigen ranges between approximately 14 to 18 nM. The CD20 antigen is expressed on pre-B and mature B lymphocytes and on > 90% of B-cell non-Hodgkin’s lymphomas (NHL). The CD20 antigen is not shed from the cell surface and does not internalize upon antibody binding. The chelate tiuxetan, which tightly binds Y-90, is covalently linked to ibritumomab. The beta emission from Y-90 induces cellular damage by the formation of free radicals in the target and neighboring cells.
Indications
- 1 INDICATIONS AND USAGE Zevalin is a CD20-directed radiotherapeutic antibody administered as part of the Zevalin therapeutic regimen indicated for the treatment of adult patients with: relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL) ( 1.1 ). previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy ( 1.2 ). 1.1 Relapsed or Refractory, Low-grade or Follicular NHL Zevalin is indicated for the treatment of adult patients with relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). 1.
Common Doses
- 250 mg
- 650 mg
- 50 mg
- 400 mg
Dosage
2 DOSAGE AND ADMINISTRATION Day 1 : Administer rituximab 250 mg/m 2 intravenous infusion. ( 2.2 ) Day 7, 8, or 9 : Administer rituximab 250 mg/m 2 intravenous infusion. ( 2.2 ) If platelets at least 150,000/mm 3 : Within 4 hours after rituximab infusion, administer 0.4 mCi/kg (14.8 MBq per kg) Y-90 Zevalin intravenous infusion. If platelets 100,000 to 149,000/mm 3 in relapsed or refractory patients: Within 4 hours after rituximab infusion, administer 0.3 mCi/kg (11.1 MBq per kg) Y-90 Zevalin intravenous infusion. 2.
Black Box Warning
WARNING: SERIOUS INFUSION REACTIONS, PROLONGED AND SEVERE CYTOPENIAS, and SEVERE CUTANEOUS AND MUCOCUTANEOUS REACTIONS Serious Infusion Reactions: Deaths have occurred within 24 hours of rituximab infusion, an essential component of the Zevalin therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most (80%) fatalities occurred with the first rituximab infusion [ see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 ) ] .
Contraindications
- 4 CONTRAINDICATIONS None. None.
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the label: Serious Infusion Reactions [ see Boxed Warning and Warnings and Precautions ( 5.1 ) ] . Prolonged and Severe Cytopenias [ see Boxed Warning and Warnings and Precautions ( 5.2 ) ]. Severe Cutaneous and Mucocutaneous Reactions [ see Boxed Warning and Warnings and Precautions ( 5.3 ) ]. Leukemia and Myelodysplastic Syndrome [ see Warnings and Precautions ( 5.4 ) ].
Interactions
- 7 DRUG INTERACTIONS Patients receiving medications that interfere with platelet function or coagulation should have more frequent laboratory monitoring for thrombocytopenia. No formal drug interaction studies have been performed with Zevalin. Monitor patients receiving medications that interfere with platelet function or coagulation more frequently for thrombocytopenia. ( 7 )