ibritumomab tiuxetan


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ibritumomab tiuxetan

 [i″brĭ-tu-mo´mab ti-uk´sĕ-tan]
a radiopharmaceutical agent consisting of the monoclonal antibodyrituximab conjugated with yttrium 90C208; used in treatment of refractory lymphomas that are positive for CD20 antigen (see CD antigen).

ibritumomab tiuxetan

Zevalin

Pharmacologic class: Monoclonal antibody

Therapeutic class: Antineoplastic

Pregnancy risk category D

Step 1: Single I.V. infusion of 250 mg/m2 rituximab at 50 mg/hour; in absence of infusion reactions, increase rate in 50-mg/hour increments q 30 minutes, to a maximum of 400 mg/hour. Immediately stop rituximab infusion for serious infusion reactions and discontinue Zevalin therapeutic regimen. Temporarily slow or interrupt rituximab infusion for less severe infusion reactions. If symptoms improve, continue infusion at one-half the previous rate.

Step 2: On day 7, 8, or 9, rituximab 250 mg/m2 I.V. at initial rate of 100 mg/hour. Increase rate by 100-mg/hour increments at 30-minute intervals, to a maximum of 400 mg/hour as tolerated. If infusion reactions occurred during rituximab infusion on day 1 of treatment, administer rituximab at initial rate of 50 mg/hour and escalate infusion rate in 50-mg/hour increments every 30 minutes to a maximum of 400 mg/hour. Administer Y-90 Zevalin injection through free-flowing I.V. line within 4 hours after completion of rituximab infusion. Use a 0.22-micron, low-protein-binding in-line filter between syringe and infusion port. After injection, flush line with at least 10 ml of normal saline.

FDA Box Warning

• Deaths have occurred within 24 hours of rituximab infusion, an essential component of Zevalin therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infitrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most fatalities (80%) occurred with first rituximab infusion. Discontinue rituximab and Y-90 Zevalin infusions in patients who develop severe infusion reactions.

• Y-90 Zevalin administration causes severe and prolonged cytopenias in most patients. Don't administer Y-90 Zevalin to patients with 25% or greater lymphoma marrow involvement or impaired bone marrow reserve.

• Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the Zevalin therapeutic regimen. Discontinue rituximab and Y-90 Zevalin infusions in patients experiencing severe cutaneous or mucocutaneous reactions.

• Dosage of Y-90 Zevalin shouldn't exceed 32.0 mCi (1,184 MBq).

Action

Binds indium-111 (In-111) or yttrium-90 (Y-90) with free amino groups of lysines and arginines within antibody; binds specifically to CD20 antigen, found on surface of normal and malignant B lymphocytes. Radioactive component of Y-90 causes cellular damage via free radicals in target cells.

Availability

Injection: 3.2 mg/2 ml (two Zevalin kits containing four vials each)

Indications and dosages

Relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL); previously untreated follicular NHL in patients who achieve partial or complete response to first-line chemotherapy

Adults: Two-step regimen that includes pre-dose of rituximab

Step 1: Single I.V. infusion of 250 mg/m2 rituximab at 50 mg/hour; in absence of infusion reactions, increase rate in 50-mg/hour increments q 30 minutes, to a maximum of 400 mg/hour. Immediately stop rituximab infusion for serious infusion reactions and discontinue Zevalin therapeutic regimen. Temporarily slow or interrupt rituximab infusion for less severe infusion reactions. If symptoms improve, continue infusion at one-half the previous rate.

Step 2: On day 7, 8, or 9, rituximab 250 mg/m2 I.V. at initial rate of 100 mg/hour. Increase rate by 100-mg/hour increments at 30-minute intervals, to a maximum of 400 mg/hour as tolerated. If infusion reactions occurred during rituximab infusion on day 1 of treatment, administer rituximab at initial rate of 50 mg/hour and escalate infusion rate in 50-mg/hour increments every 30 minutes to a maximum of 400 mg/hour. Administer Y-90 Zevalin injection through free-flowing I.V. line within 4 hours after completion of rituximab infusion. Use a 0.22-micron, low-protein-binding in-line filter between syringe and infusion port. After injection, flush line with at least 10 ml of normal saline.

If platelet count is 150,000/mm3 or greater, administer Y-90 Zevalin over 10 minutes as an I.V. injection at a dose of Y-90 0.4 mCi/kg (14.8 MBq/kg) actual body weight. If platelet count is 100,000/mm3 to 149,000/mm3 in relapsed or refractory patients, administer Y-90 Zevalin over 10 minutes as an I.V. injection at a dose of Y-90 0.3 mCi/kg (11.1 MBq/kg) actual body weight. Don't administer more than 32 mCi (1,184 MBq) Y-90 Zevalin dose regardless of patient's body weight.

Contraindications

None

Precautions

Use cautiously in:
• cardiac conditions
• elderly patients
• pregnant or breastfeeding patients.

Administration

Don't administer to patients with lymphoma marrow involvement at or above 25% or impaired bone marrow reserve.

Assess for human antimurine antibody before treatment. If result is positive, patient may experience hypersensitivity reaction.
• Premedicate patient with acetaminophen and diphenhydramine, as ordered, before each rituximab infusion.
• Know that ibritumomab should be used only as part of a regimen that combines ibritumomab and rituximab.

Give ibritumomab by slow I.V. infusion over 10 minutes; monitor closely.

Don't give by I.V. push.

Take steps to prevent extravasation of Y-90 Zevalin. If extravasation occurs, immediately stop infusion and restart in another vein.
• Don't give Y-90 Zevalin if platelet count is less than 100,000/mm3.

Immediately and permanently discontinue drug if severe infusion reaction occurs (urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, cardiogenic shock). Temporarily slow or interrupt rituximab infusion for less severe infusion reactions.

Discontinue drug if severe cutaneous or mucocutaneous reactions develop.
• Follow facility policy on radiation precautions to protect patients, visitors, and medical personnel from radiation exposure.

Adverse reactions

CNS: dizziness, anxiety, headache, insomnia, asthenia

CV: hypotension, peripheral edema

EENT: rhinitis, epistaxis, throat irritation

GI: nausea, vomiting, diarrhea, constipation, anorexia, dyspepsia, abdominal pain or enlargement, melena

Hematologic: anemia, thrombocytopenia, neutropenia, pancytopenia, hemorrhage, myelodysplastic syndrome, acute myelogenous leukemia

Musculoskeletal: joint pain, myalgia, back pain

Respiratory: increased cough, dyspnea, apnea, bronchospasm

Skin: flushing, bruising, diaphoresis, petechiae, pruritus, rash, urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, exfoliative dermatitis

Other: bacterial infection, I.V. site irritation, fever, chills, generalized pain, tumor pain, hypersensitivity reactions including anaphylaxis, myeloid malignancies, dysplasias, serious infusion reactions

Interactions

None significant

Patient monitoring

Institute infection control protocols. Protect patient from potential sources of infection.

Assess CBC and platelet count before starting therapy. Monitor regularly during and after therapy.

Monitor patient for hypersensitivity reactions, which can be fatal and usually occur within 30 minutes to 2 hours of administration.
• Be alert for unusual bleeding or bruising.

Patient teaching

Instruct patient to promptly report difficulty breathing, rash, fever, chills, severe GI distress, black tarry stools, illness or injury, or unusual bleeding or bruising.
• Tell patient that drug increases his risk of infection. Instruct him to avoid crowds and potential or known sources of infection.
• Advise patient to eat small, frequent meals and take antiemetic drugs to control nausea and vomiting, as needed and prescribed.
• Advise patient that he'll undergo blood testing during therapy to monitor drug effects.
• Advise patient not to receive live viral vaccines during or immediately after taking this drug.
• As appropriate, review all other significant and life-threatening adverse reactions mentioned above.

ibritumomab tiuxetan

a monoclonal antibody radioimmunotherapy used as part of a regimen for non-Hodgkin's lymphoma.
References in periodicals archive ?
Compared with ibritumomab tiuxetan, the radiation dose accumulated in the liver is lower but the dose accumulated in kidneys is higher.
7 Beta 12 Y-90 ibritumomab tiuxetan (Zevalin) I-131 8.
11) Currently, 2 radiolabelled antibodies are available for treatment of follicular non-Hodgkin's lymphoma, Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar).
Yttrium90, Iodine131, ibritumomab tiuxetan are the currently used radioimmunoconjugates.
The antineoplastic agents are alemtuzumab (Campath), bevacizumab (Avastin), cetuximab (Erbitux), gemtuzumab ozogamicin (Mylotarg), ibritumomab tiuxetan (Zevalin), panitumumab (Vectibix), tositumomab and iodine 131 (Bexxar), and trastuzumab (Herceptin).
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.
Treatment with ibritumomab tiuxetan radio-immunotherapy in patients with rituximabrefractory non-Hodgkin's lymphoma.
Phase I Trial of (90)Yttrium Ibritumomab Tiuxetan (RIT) with Autologous Stem Cell Transplantation (ASCT) in Patients with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma, Abstract 8565
90)Yttrium Ibritumomab Tiuxetan Combined with High-dose BEAM Chemotherapy and Autologous Stem Cell Transplantation for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma, Abstract 8615