ibritumomab tiuxetan

ibritumomab tiuxetan,

an immunoconjugate of ibritumomab and the linker-chelator tiuxetan, used as part of a regimen for non-Hodgkin's lymphoma in conjunction with the monoclonal antibody rituximab and the radiopharmaceutics indium 111 and yttrium 90.

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ibritumomab tiuxetan Warning - Hazardous drug!

Zevalin

Pharmacologic class: Monoclonal antibody

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Boxed Warning

• Deaths from infusion reactions have occurred within 24 hours of infusion of rituximab (essential component of ibritumomab tiuxetan regimen), with roughly 80% occurring after first infusion. Signs and symptoms include hypoxia, pulmonary infiltrate, adult respiratory distress syndrome, myocardial infarction, ventricular fibrillation, and cardiogenic shock. If infusion reaction occurs, discontinue rituximab, In-111 Zevalin, and Y-90 Zevalin infusions and provide supportive treatment.
• Y-90 Zevalin regimen causes severe, prolonged cytopenias in most patients. Don't give to patients with 25% or greater lymphoma bone marrow involvement or impaired marrow reserve, (such as those who've had previous myeloablative therapy or those with platelet counts below 100,000/mm³, neutrophil counts below 1,500/mm³, or hypocellular bone marrow or marked reduction in bone marrow precursors).
• Ibritumomab tiuxetan regimen has caused severe cutaneous and mucocutaneous reactions, with some deaths. Patients experiencing such reactions shouldn't receive further regimen components and should seek prompt medical evaluation.
• Don't exceed maximum Y-90 Zevalin dose of 32 mCi (1,184 MBq).
• Y-90 Zevalin should not be given to patients with altered biodistribution, as determined by In-111 Zevalin imaging.
• In-111 Zevalin and Y-90 Zevalin should be used only by healthcare professionals qualified in safe radionuclide use and handling.

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

➣ Non-Hodgkin's lymphoma

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; increase rate by 50 mg/hour q 30 minutes, to a maximum of 400 mg/hour. If hypersensitivity or infusion-related reaction occurs, slow or interrupt infusion; if symptoms improve, may resume at 50% of previous rate. Within 4 hours of rituximab dose, 5 mCi of In-111 Zevalin I.V. should be given over 10 minutes.

Step 2: 7 to 9 days after step 1, I.V. infusion of 250 mg/m² rituximab at 100 mg/hour (50 mg/hour if infusion-related reaction occurred during first rituximab dose); increase by 100 mg/hour q 30 minutes, to a maximum of 400 mg/hour, as tolerated. Within 4 hours of rituximab dose, give 0.3 to 0.4 mCi/kg of Y-90 Zevalin I.V. over 10 minutes, not to exceed absolute maximum allowable dose of 32 mCi.

Contraindications

• Hypersensitivity to any drug in therapeutic regimen or its components or to murine products
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• cardiac conditions
• elderly patients.

Administration

☞ 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.
• Follow facility policy on radiation precautions to protect patients, visitors, and medical personnel from radiation exposure.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

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

Musculoskeletal: joint pain, myalgia, back pain

Respiratory: increased cough, dyspnea, apnea, bronchospasm

Skin: flushing, bruising, diaphoresis, petechiae, pruritus, rash, urticaria, angioedema

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

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 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.
• As appropriate, review all other significant and life-threatening adverse reactions mentioned above.