Zevalin

Generic Name: Ibritumomab Tiuxetan
Class: Antineoplastic Agents
VA Class: AN600
Chemical Name: N - [2 - [bis(carboxymethyl)amino] - 3 - (4 - isothiocyanatophenyl)propyl] - N - [2 - [bis(carboxymethyl)amino]propyl] glycine conjugate dimer disulfide with mouse monoclonal IDEC-Y2B8k-chain anti-(human CD20 (antigen)) (mouse monoclonal IDEC-Y2B8 γ1-chain) immuglobulin G1
CAS Number: 206181-63-7

• Experience of Supervising Clinician


• 
  

  Use only by qualified clinicians experienced in the safe use and handling of radionuclides.^{1 7}

  
  

• Rituximab-related Infusion Reactions


• 
  

  Fatalities have occurred within 24 hours following rituximab infusion, an essential component of the ibritumomab tiuxetan therapeutic regimen.^{1 2}

  
  


• 
  

  Fatalities were associated with an infusion reaction symptom complex that included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, and/or cardiogenic shock.¹

  
  


• 
  

  Approximately 80% of fatal infusion reactions occurred with initial infusion of rituximab.^{1 4}

  
  


• 
  

  If severe infusion-related effects develop, discontinue rituximab, indium In 111 ibritumomab tiuxetan, and yttrium Y 90 ibritumomab tiuxetan, and initiate appropriate therapy.¹ (See Infusion-related Effects under Cautions.)

  
  

• Cytopenias


• 
  

  Most patients receiving the ibritumomab tiuxetan therapeutic regimen develop prolonged and severe cytopenias.¹

  
  

• 
  

  Do not use in patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve.¹ (See Hematologic Effects under Cautions.)

  
  

• Severe Cutaneous and Mucocutaneous Reactions


• 
  

  Severe, sometimes fatal, cutaneous and mucocutaneous reactions reported.^{1 11} (See Severe Cutaneous and Mucocutaneous Reactions under Cautions.)

  
  

• 
  

  If severe cutaneous or mucocutaneous reactions occur, discontinue rituximab, indium In 111 ibritumomab tiuxetan, and yttrium Y 90 ibritumomab tiuxetan.^{11 b}

  
  

• Yttrium Y 90 Ibritumomab Tiuxetan


• 
  

  Do not administer yttrium Y 90 ibritumomab tiuxetan to patients with altered distribution as determined by imaging with indium In 111 ibritumomab tiuxetan.¹

  
  


• 
  

  Dosage of yttrium Y 90 ibritumomab tiuxetan should not exceed 32 mCi.¹

  
  

Introduction

Radioimmunotherapeutic agent; a murine anti-human antigen CD20 monoclonal antibody (conjugated with the chelating agent tiuxetan) that readily chelates the radioisotopes indium 111 and yttrium 90.^{1 2 3 5 7}

Uses for Zevalin

Non-Hodgkin’s Lymphoma

Part of a specific therapeutic regimen (ibritumomab tiuxetan therapeutic regimen) for treatment of relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma, including follicular non-Hodgkin’s lymphoma that is refractory to rituximab therapy (designated an orphan drug by FDA for this use).^{1 2 12}

Part of a specific therapeutic regimen (ibritumomab tiuxetan therapeutic regimen) for the treatment of relapsed or refractory, low-grade, follicular B-cell non-Hodgkin's lymphoma in patients that are rituximab-naive.^b

Efficacy determined based on overall response rates; actual clinical benefits (e.g., effects on survival) not clearly elucidated.¹

Ibritumomab tiuxetan therapeutic regimen may be associated with higher overall response rate than rituximab monotherapy;^{1 5 6 9} however, median duration of response and median time to disease progression were similar between the 2 groups in one study.^{1 9}

Safety and efficacy not evaluated in patients with ≥25% involvement of bone marrow by lymphoma and/or impaired bone marrow reserve (e.g., prior myeloablative therapies, prior external beam radiation to >25% of active marrow, platelet count <100,000/mm³, neutrophil count <1500/mm³).^{1 5}

Zevalin Dosage and Administration

General

• 
  

  Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.

  
  


• 
  

  The ibritumomab tiuxetan therapeutic regimen consists of 2 low doses of rituximab (to deplete peripheral B lymphocytes and to improve distribution of ibritumomab tiuxetan), an imaging dose of indium In 111 ibritumomab tiuxetan coupled with one or more whole body scans (to assess distribution), and a therapeutic dose of yttrium Y 90 ibritumomab tiuxetan.^{1 2 3 5 7} Regimen administered in 2 steps.¹

  
  


• 
  

  Intended for use as a single course of treatment.¹ Safety of multiple courses or of other forms of therapeutic irradiation preceding, following, or in combination with ibritumomab tiuxetan therapeutic regimen not established.¹

  
  


• 
  

  Do not use in absence of rituximab predose.¹ Dose of rituximab is lower when used as part of ibritumomab tiuxetan therapeutic regimen than when used alone.¹

  
  


• 
  

  To minimize risk of infusion-related reactions, consider oral premedication with acetaminophen 650 mg and an antihistamine (e.g., diphenhydramine, 50 mg) prior to each infusion of rituximab.^{1 4 b}

  
  


• 
  

  Distribution is restricted.² (See Preparations.)

  
  

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Rituximab Administration

Administer rituximab by IV infusion; rituximab must be diluted prior to IV infusion.^{1 4} Do not administer by rapid IV injection (e.g., IV push or bolus).¹

Consult manufacturer’s labeling for additional information on the reconstitution and administration of rituximab.¹

Ibritumomab Tiuxetan Administration

Administer indium In 111 ibritumomab tiuxetan and yttrium Y 90 ibritumomab tiuxetan by slow IV injection.^{1 5 7}

A 0.22-mcm low-protein-binding filter should be inline between syringe and infusion port prior to injection of indium In 111 ibritumomab tiuxetan.¹ Following injection, flush line with at least 10 mL of 0.9% sodium chloride solution.¹

Observe standard precautions to avoid extravasation of yttrium Y 90 ibritumomab tiuxetan (e.g., establish free-flowing IV line prior to administration).¹ Monitor infusion site for signs of extravasation; if manifestations of extravasation appear, immediately stop infusion, restart infusion in another limb, and consult radiation safety officer.^{1 2 b}

Yttrium Y 90 ibritumomab tiuxetan can be routinely administered on an outpatient basis.^{1 2 7} Presumably low risk of exposure to radiation in health-care professionals, family members, and other close personal contacts.^{2 7} Standard precautions for reducing risk of radiation exposure not necessary;² however, some clinicians recommend following universal precautions for minimizing exposure to blood and other body fluids (e.g., saliva, urine, stool).⁷

Preparation of Radiolabeled Ibritumomab Tiuxetan

Instructions for preparation of indium In 111 ibritumomab tiuxetan and yttrium Y 90 ibritumomab tiuxetan solutions differ.¹ Changing the recommended ratio of any reactant in the radiolabeling process may adversely affect therapeutic results.¹

Consult manufacturer’s labeling for detailed information on preparation of indium In 111 ibritumomab tiuxetan and yttrium Y 90 ibritumomab tiuxetan.¹

Rate of Administration

Rituximab step 1: Administer at initial rate of 50 mg/hour.¹ If no infusion reactions occur, increase infusion rate in 50 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour.^b

Rituximab step 2: If no infusion reaction occurred during step 1, administer at an initial rate of 100 mg/hour.¹ Increase infusion rate in 100 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour as tolerated.^b

If infusion reaction occurred during step 1, administer at an initial rate of 50 mg/hour.^b Increase infusion rate in 50 mg/hour increments every 30 minutes, to a maximum rate of 400 mg/hour.^b

If hypersensitivity reactions and/or infusion-related events develop, reduce infusion rate or temporarily interrupt infusion; when symptoms improve, resume infusion at one-half previous rate.¹ (See Infusion-related Effects under Cautions.)

Indium In 111 ibritumomab tiuxetan or yttrium Y 90 ibritumomab tiuxetan: administer over 10 minutes.¹

Dosage

Available as ibritumomab tiuxetan; dosage expressed in terms of ibritumomab tiuxetan.¹

Adults

Non-Hodgkin’s Lymphoma

IV

Step 1 (day 1): 250 mg/m² rituximab, then (within 4 hours) 5 mCi (1.6 mg total antibody dose) indium In 111 ibritumomab tiuxetan.¹ To determine distribution of indium In 111 ibritumomab tiuxetan, perform whole body scans at 48–72 hours following imaging dose and, if necessary, at other time points;¹ do not proceed with therapy in patients with altered distribution.¹ (See Altered Distribution under Cautions.)

Step 2 (7, 8, or 9 days after Step 1): a second 250-mg/m² dose of rituximab, then (within 4 hours) 0.4 mCi/kg (up to a maximum dose of 32 mCi) yttrium Y 90 ibritumomab tiuxetan (for patients with normal platelet counts ≥150,000/mm³) or 0.3 mCi/kg yttrium Y 90 ibritumomab tiuxetan (for patients with platelet counts of 100,000–149,000/mm³).^{1 2 5 b}

Prescribing Limits

Adults

Non-Hodgkin’s Lymphoma

IV

Yttrium Y 90 ibritumomab tiuxetan: maximum 32 mCi regardless of patient’s weight.^{1 5}

Special Populations

No special population dosage recommendations at this time.^b (See Geriatric Use under Cautions.)

Cautions for Zevalin

Contraindications

• 
  

  Known hypersensitivity to ibritumomab tiuxetan, murine proteins, rituximab, indium chloride, yttrium chloride, or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Infusion-related Effects

Risk of severe, potentially fatal infusion-related effects associated with rituximab infusion.¹ Onset of most severe reactions between 30–120 minutes after starting first rituximab infusion;^{1 4} fatalities reported within 24 hours of infusion.¹ (See Boxed Warning.)

If severe infusion-related effects (e.g., urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, cardiogenic shock) develop, discontinue rituximab, indium In 111 ibritumomab tiuxetan, or yttrium Y 90 ibritumomab tiuxetan and initiate appropriate therapy.^{1 4 b}

For less severe infusion reactions, temporarily slow or interrupt rituximab infusion; if symptoms improve, continue at half the previous rate.¹ (See Rate of Administration under Dosage and Administration.)

Monitor closely for extravasation during infusion of ibritumumab tiuxetan.^b If signs or symptoms of extravasation occur, immediately terminate the infusion and restart in another limb.^b (See Ibritumomab Tiuxetan Administration under Dosing and Administration.)

Hematologic Effects

Severe and prolonged cytopenia (e.g., thrombocytopenia, neutropenia, anemia) occurs in most patients;^{1 2} filgrastim, erythropoietin, platelet transfusions, or red blood cell transfusions required in some patients.^{1 2 6}

Median time to nadir neutrophil or platelet count or nadir hemoglobin concentration was 7–9 weeks; median duration of cytopenia was 22–35 days.¹ Possible prolonged severe cytopenia (>12 weeks following treatment).¹

Risk of hemorrhage, including fatal cerebral hemorrhage.¹ Carefully monitor hematologic function and promptly manage cytopenias and their complications (e.g., febrile neutropenia, hemorrhage) for up to 3 months following completion of therapy.¹

Do not use in patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve (as indicated by prior myeloablative therapies, platelet count <100,000/mm³, neutrophil count <1500/mm³, hypocellular bone marrow [cellularity ≤15% or marked reduction in bone marrow precursor cells]), or in patients with history of failed stem cell collection.^{1 2} (See Hematologic Monitoring under Cautions.)

Severe Cutaneous and Mucocutaneous Reactions

Severe, sometimes fatal, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, and exfoliative dermatitis reported.^{1 11} Reaction may be acute (developing within days) or delayed (e.g., 3–4 months).^{1 11}

Patients experiencing a severe cutaneous or mucocutaneous reaction should not receive any further components of the ibritumomab tiuxetan therapeutic regimen and should promptly seek medical evaluation.^{1 11}

Other Warnings and Precautions

Concomitant Use with Rituximab

When used in therapeutic regimen with rituximab, consider the cautions, precautions, and contraindications associated with rituximab.¹

Secondary Leukemia and Myelodysplastic Syndrome

Secondary malignancies (e.g., meningioma, myelodysplastic syndrome, acute myelogenous leukemia) may develop.^{1 2 6} Median time to diagnosis following treatment in expanded access program or clinical studies was 1.5 or 2.9 years, respectively.¹ Cumulative incidence increasing with longer follow-up.¹

Risk of developing secondary malignancies not associated with the number of prior treatments.^{1 14} Multiple cytogenetic abnormalities reported, most commonly involving chromosomes 5 and/or 7.¹

Altered Distribution

Do not administer yttrium Y 90 ibritumomab tiuxetan in patients with altered distribution of ibritumomab tiuxetan (as determined by imaging studies with indium In 111 ibritumomab tiuxetan).¹ Assess biodistribution with images at 48–72 hours following injection.¹

Altered biodistribution of indium In 111 ibritumomab tiuxetan is characterized by intense localization of radiotracer in liver, spleen, and bone marrow indicative of reticuloendothelial system uptake or by increased uptake in normal organs not involved by tumor as indicated by diffuse uptake in normal lung more intense than that in liver; greater intensity in kidneys than in liver on posterior view; fixed areas (unchanged with time) of uptake in normal bowel greater than uptake in liver; or prominent bone marrow uptake, characterized by clear visualization of long bones and ribs (seen in <0.5% of patients).¹ (See Distribution under Pharmacokinetics.)

Safety and efficacy of administration of yttrium Y 90 ibritumomab tiuxetan in patients with prominent bone marrow uptake not established.¹ Consider possible causes of prominent bone marrow uptake (e.g., bone marrow involvement by lymphoma, increased marrow activity due to recent hematopoietic growth factor administration, increased reticuloendothelial uptake in patients with human antimurine antibodies [HAMA] and human antichimeric antibody [HACA]); reassess biodistribution after correction of underlying factors.¹ Do not administer yttrium Y 90 ibritumomab tiuxetan in patients with persistently prominent marrow uptake on repeat biodistribution scans.¹

Fetal/Neonatal Morbidity and Mortality

Yttrium Y 90 ibritumomab tiuxetan may cause fetal harm.¹ Avoid pregnancy during therapy and for up to 12 months following completion of therapy.^{1 2} If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹ (See Advice to Patients.)

Creutzfeldt-Jakob Disease and Viral Diseases

Because indium In 111 ibritumomab tiuxetan and yttrium Y 90 ibritumomab tiuxetan contain albumin human, the preparations carry an extremely remote risk for transmitting viral diseases or Creutzfeldt-Jakob disease.¹ No cases of transmission of viral diseases or Creutzfeldt-Jakob disease reported with albumin human.¹

Infectious Complications

Risk of severe (e.g., urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, upper respiratory tract infection) or life-threatening infections (e.g., sepsis, empyema, pneumonia, febrile neutropenia, fever, biliary stent-associated cholangitis); may occur up to 4 years following completion of therapy.^{1 2}

Sensitivity Reactions

Anaphylactic and other hypersensitivity reactions reported following IV administration of proteins.¹

Drugs for treatment of hypersensitivity reactions, including epinephrine, antihistamines, and corticosteroids, should be available for immediate use in case of a reaction during administration of ibritumomab tiuxetan therapeutic regimen.^{1 4 7}

Patients who have received murine proteins should be screened for HAMA.¹ Safety not studied in patients with evidence of HAMA; such patients may be at increased risk of allergic or serious hypersensitivity reactions during administration of ibritumomab tiuxetan therapeutic regimen.¹

Radionuclide Precautions

Contents of ibritumomab tiuxetan kits are not radioactive.¹ However, employ institutional good radiation safety practices and patient management procedures during and after radiolabeling of ibritumomab tiuxetan with indium 111 or yttrium 90 to minimize exposure of patients and medical personnel to radiation.¹

Immunologic Effects

Positive HAMA or HACA responses detected following ibritumomab tiuxetan therapeutic regimen.^{1 2 3 6} HAMA/HACA responses develop rarely, are typically transient, and do not increase with time.^b

Hematologic Monitoring

Following completion of therapy, monitor CBCs and platelet counts weekly until levels return to normal;² more frequent monitoring required in patients who develop severe cytopenia or as clinically indicated.¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether ibritumomab tiuxetan is distributed into milk.¹ However, human IgG is excreted in human milk, therefore, manufacturer states ibritumomab would be expected to be present in human milk.^b Discontinue nursing or do not administer regimen.^b

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 2}

Geriatric Use

No overall differences relative to younger adults, but increased sensitivity cannot be ruled out.¹

Hematologic Impairment

Do not administer ibritumomab tiuxetan therapeutic regimen to patients with hematologic impairment.^{1 2} (See Hematologic Effects under Cautions.)

Common Adverse Effects

Thrombocytopenia,^{1 2 9} neutropenia,^{1 2 9} anemia,^{1 2 9} asthenia,^{1 2 7 9} nausea,^{1 2 7 9} infection,^{1 7} chills,^{1 2 7 9} fever,^{1 2 7 9} abdominal pain,^{1 2 7 9} dyspnea,^{1 2 9} pain,^{1 2 9} headache,^{1 2 9} vomiting,^{1 2 9} throat irritation,^{1 2 9} dizziness,^{1 2 9} increased cough.^{1 2 9}

Interactions for Zevalin

No formal drug interaction studies to date.¹

Specific Drugs

Drug	Interaction	Comments
Anticoagulants	Possible increased risk of thrombocytopenia, bleeding, and hemorrhage1	More frequent laboratory monitoring for thrombocytopenia and modification of transfusion practices recommended; weigh risk versus benefit of concomitant administration1
Drugs affecting platelet function	Possible increased risk of thrombocytopenia, bleeding, and hemorrhage1	More frequent laboratory monitoring for thrombocytopenia and modification of transfusion practices recommended;1 weigh risk versus benefit of concomitant administration1
Hematopoietic growth factors	Altered biodistribution of ibritumomab (increased uptake in bone marrow) may occur due to increased marrow activity from recent administration of hematopoietic growth factors1	In clinical studies, use of growth factors was prohibited 2 weeks before and after completion of regimen1
Vaccines	Safety of immunization with live virus vaccines following therapy not studied1 Ability of patients receiving ibritumomab tiuxetan therapeutic regimen to generate primary or anamnestic humoral response to any vaccine not studied1	Do not administer live viral vaccines for 12 months following the ibritumomab tiuxetan therapeutic regimenb

Zevalin Pharmacokinetics

Absorption

Onset

Median number of circulating B cells drops to 0 (range: 0–1084 cells/mm³) at 4 weeks following treatment.¹

Distribution

Extent

Binding observed on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, lymphoid follicles of the tonsil, and lymphoid nodules of other organs (e.g., large and small intestines).^{1 2} Little or no binding observed on nonlymphoid or gonadal tissues.^{1 2}

Normal distribution is characterized by faintly visible uptake of indium In 111 ibritumomab tiuxetan in blood pool areas (i.e., heart, abdomen, neck, extremities); moderately high to high uptake in normal liver and spleen; moderately low or very low uptake in normal kidneys, urinary bladder, and normal (uninvolved) bowel; nonfixed areas within bowel lumen that change position with time; or focal fixed areas of uptake in bowel wall (localized to lymphoid aggregates in bowel wall).¹

Human IgG distributed into milk.¹ Not known whether ibritumomab tiuxetan is distributed into milk.¹

Elimination

Elimination Route

Approximately 7.2% of injected dose of yttrium Y 90 ibritumomab tiuxetan is excreted in urine within 7 days.^{1 2 7}

Half-life

Indium 111: physical half-life is 67.3 hours (2.81 days).¹

Yttrium 90: physical half-life is 64.1 hours (2.67 days).¹ Mean effective half-life in blood is 30 hours; mean area under the fraction of injected activity-time curve in blood is 39 hours.¹

Stability

Storage

Parenteral

Injection

Indium In 111 ibritumomab tiuxetan: 2–8°C; do not freeze.¹ Administer within 12 hours of radiolabeling.¹

Yttrium Y 90 ibritumomab tiuxetan: 2–8°C; do not freeze.¹ Administer within 8 hours of radiolabeling.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility¹

Compatible
Sodium acetate
Sodium chloride 0.9%

ActionsActions

• 
  

  Ibritumomab tiuxetan radiolabeled with indium 111 (indium In 111 ibritumomab tiuxetan) is used for imaging purposes; ibritumomab tiuxetan radiolabeled with yttrium 90 (yttrium Y 90 ibritumomab tiuxetan) is used for radioimmunotherapy.^{1 2 3 5 7}

  
  


• 
  

  Ibritumomab binds specifically to antigen CD20 (expressed on normal pre-B and mature B lymphocytes and on essentially all B-cell non-Hodgkin’s lymphomas),^{1 2} triggering apoptosis of normal and malignant B cells through complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.^{1 2}

  
  


• 
  

  Yttrium 90 responsible for the primary cytotoxic effect of yttrium Y 90 ibritumomab tiuxetan; induces cellular damage by forming free radicals in target and neighboring cells.^{1 2}

  
  


• 
  

  Median number of circulating B cells drops to 0 (range: 0–1084 cells/mm³) at 4 weeks following completion of therapy.¹ Recovery of B cells begins at approximately 3 months; median levels of B cells return to normal by 9 months.^{1 2} Median serum concentrations of IgG and IgA remain within normal range throughout the period of B-cell depletion; median serum IgM concentrations decline to below normal values but return to normal by 6 months following treatment.¹

  
  

Advice to Patients

• 
  

  Importance of advising family members and other close contacts to follow standard precautions for minimizing exposure to blood and other body fluids (e.g., saliva, urine, stool).^{2 7}

  
  


• 
  

  Importance of taking premedications as prescribed.^b

  
  


• 
  

  Importance of promptly seeking medical attention if severe signs or symptoms of an infusion reaction occur.^b (See Infusion-related Effects under Cautions.)

  
  


• 
  

  Importance of promptly seeking medical attention if severe cutaneous or mucocutaneous reaction develops (e.g., diffuse rash, bullae, or desquamation of the skin or oral mucosa).^{11 b}

  
  


• 
  

  Importance of promptly reporting to a clinician any signs or symptoms of cytopenias (e.g., bleeding, easy bruising, petechiae or purpura, pallor, weakness or fatigue).^b

  
  


• 
  

  Importance of immediately reporting any signs or symptoms of infection (e.g., fever).^b

  
  


• 
  

  Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.¹ Necessity of advising women to use an effective method of contraception while receiving therapy and for up to 12 months following completion of therapy.¹ Necessity of advising pregnant women of risk to the fetus.¹ Importance of discontinuing nursing during and after therapy.^b

  
  


• 
  

  Importance of not receiving live viral vaccines for 12 months after completion of the ibritumomab tiuxetan therapeutic regimen.^b

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs (e.g., live viral vaccines, medications that interfere with platelet function or coagulation) and dietary or herbal supplements, as well as any concomitant illnesses.^{1 b} (See Interactions.)

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Distribution restricted to qualified and appropriately licensed clinicians and facilities equipped to handle radionuclides (e.g., nuclear pharmacies); not available through community pharmacies.²

Commercially available as 2 separate and distinctly labeled kits (In-111-Zevalin and Y-90-Zevalin) that contain all nonradioactive ingredients necessary to prepare a single dose of indium In 111 ibritumomab tiuxetan and a single dose of yttrium Y 90 ibritumomab tiuxetan.¹ Indium 111 chloride must be ordered separately, from either GE Healthcare or Mallinckrodt Inc., at the time the indium In 111 ibritumomab tiuxetan (In-111-Zevalin) kit is ordered; yttrium 90 chloride sterile solution is supplied by MDS Nordion when the yttrium Y 90 ibritumomab tiuxetan (Y-90-Zevalin) kit is ordered.¹ Rituximab must be ordered separately.¹

Ibritumomab Tiuxetan

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Kit	1 Vial, 3.2 mg/2 mL, Injection, for preparation of radioactive pharmaceutical, Ibritumomab Tiuxetan (Zevalin; preservative-free) 1 Vial, 50 mM/2 mL, Sodium Acetate Injection (preservative-free) 1 Vial, Buffer Formulation Injection (with albumin; preservative-free) 1 Vial, Reaction Vial (sterile and empty)	Zevalin In-111	Biogen Idec
			Zevalin Y-90	Biogen Idec

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Biogen Idec Inc. Zevalin (ibritumomab tiuxetan) injection prescribing information. Cambridge, MA; 2007 Jan.

2. IDEC Pharmaceuticals, San Diego, CA: Personal communication.

3. Witzig TE. Radioimmunotherapy for patients with relapsed B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2001; 48(Suppl 1):S91-5. [PubMed 11587375]

4. Biogen Idec/Genentech, Inc. Rituxan (rituximab) prescribing information. San Diego/South San Francisco, CA; 2007 Feb 21.

5. Wiseman GA, White CA, Sparks RB et al. Biodistribution and dosimetry results from a phase III prospectively randomized controlled trial of Zevalin radioimmunotherapy for low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. Crit Rev Oncol Hematol. 2001; 39:181-94. [PubMed 11418315]

6. Maung K, D’Orazio AI. 6th European Hematology Association Meeting. Frankfurt, Germany. June 21-24, 2001. Clin Lymphoma. 2001; 2:74-9. [PubMed 11712544]

7. Wagner HN Jr, Wiseman GA, Marcus CS et al. Administration guidelines for radioimmunotherapy of non-Hodgkin’s lymphoma with⁹⁰Y-labeled anti-CD20 monoclonal antibody. J Nucl Med. 2002; 43:267-72. [IDIS 476756] [PubMed 11850494]

8. Witzig TE, Flinn IW, Gordon LI et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol.

9. Witzig TE, Gordon LI, Cabanillas F et al. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2002; 20:2453-63. [IDIS 486286] [PubMed 12011122]

10. Wiseman GA, Gordon LI, Multani PS et al. Ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin’s lymphoma patients with mild thrombocytopenia: a phase II multicenter trial. Blood. 2002; 99.

11. Kooijmans-Coutinho M. Dear healthcare professional letter regarding severe cutaneous or mucocutaneous reactions associated with Zevalin. Cambridge, MA: Biogen Idec; 2005 Oct. From FDA website.

12. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52.

13. Witzig TE, Molina A, Gordon LI et al. Long-term responses in patients with recurring or refractory B-cell non-Hodgkin lymphoma treated with yttrium 90 ibritumomab tiuxetan. Cancer. 2007; 109:1804-10. [PubMed 17380530]

14. Cell Therapeutics, Seattle, WA: Personal communication.

b. Biogen Idec Inc. Zevalin (ibritumomab tiuxetan) injection prescribing information. Cambridge, MA; 2008 Mar.

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