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Ibritumomab Tiuxetan

Trade Names:
Zevalin
- Injection 3.2 mg

Mechanism of Action

Pharmacology

Ibritumomab is a monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. The CD20 antigen is also expressed on more than 90% of B-cell non-Hodgkin lymphomas.

Pharmacokinetics

Absorption

The mean fraction of injected activity in the blood AUC is 39 hr.

Elimination

The mean effective t _½ for Y-90 activity in the blood is 30 hr. Over 7 days, a median of 7.2% of injected activity is excreted in urine.

Peak

At 4 wk, the median number of circulating B cells is zero (range, 0 to 1,084 cells/mm ³ ).

Duration

B-cell recovery begins at approximately 12 wk following treatment, and the median level of B cells is within the normal range (32 to 341 cells/mm ³ ) by 9 mo after treatment.

Indications and Usage

Treatment of patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin lymphoma.

Contraindications

Patients with known type I hypersensitivity or anaphylactic reactions to murine proteins or to any component of the therapeutic regimen.

Dosage and Administration

IV The therapeutic regimen consists of 2 steps. Step 1 includes a single infusion of rituximab 250 mg/m ² (not included in the therapeutic kit) preceding a fixed dose of indium-111 (In-111) ibritumomab tiuxetan 5 mCi (1.6 mg total antibody dose) administered as a 10min IV push. Step 2 follows step 1 by 7 to 9 days and consists of a second infusion of rituximab 250 mg/m ² prior to yttrium-90 (Y-90) ibritumomab tiuxetan 0.4 mCi/kg as a 10min IV push. Reduce the Y-90 ibritumomab tiuxetan dose to 0.3 mCi/kg (11.1 MBq/kg) for patients with a baseline platelet count between 100,000 and 149,000 cells/mm ³ .

General Advice

• For IV administration only.
• Inject In-111 or Y-90 ibritumomab tiuxetan within 4 hr following completion of the rituximab dose.
• Prior to injection of In-111 or Y-90 ibritumomab tiuxetan, a 0.22 micrometer low-protein-binding filter should be in-line between the syringe and the infusion port. After injection, flush the line with at least 10 mL of isotonic sodium chloride solution.
• Establish a free-flowing IV line prior to Y-90 ibritumomab tiuxetan injection.

Storage/Stability

Store at 36°F to 46°F. Do not freeze. Store In-111 ibritumomab tiuxetan at 36° to 46°F until use and administer within 12 hr of radiolabeling. Store Y-90 ibritumomab tiuxetan at 36° to 46°F until use and administer within 8 hr of radiolabeling.

Drug Interactions

None well documented. However, because of the frequent occurrence of severe and prolonged thrombocytopenia, the potential benefits of medications that interfere with platelet function or anticoagulation should be weighed against the potential increased risk of bleeding and hemorrhage.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (6%); tachycardia (less than 1%).

CNS

Headache (12%); dizziness (10%); insomnia (5%); anxiety (4%); encephalopathy, subdural hematoma (less than 1%).

Dermatologic

Pruritus (9%); rash (8%); flushing (6%); petechiae, sweats, urticaria (1% to 4%); cutaneous and mucocutaneous events (postmarketing).

EENT

Throat irritation (10%); epistaxis (3%).

GI

Nausea (31%); vomiting (12%); diarrhea (9%); anorexia (8%); abdominal enlargement, constipation (5%); dyspepsia, melena (1% to 4%); GI hemorrhage (1%).

Genitourinary

Vaginal hemorrhage (less than 1%).

Hematologic-Lymphatic

Thrombocytopenia (95%); neutropenia (77%); anemia, platelet count below 50,000 cells/mm ³ (61%); absolute neutrophil count below 1,000 cells/mm ³ (57%); ecchymosis (7%); pancytopenia (2%).

Metabolic-Nutritional

Peripheral edema (8%); angioedema (5%).

Musculoskeletal

Back pain (8%); arthralgia, myalgia (7%); arthritis (less than 1%).

Respiratory

Dyspnea (14%); increased cough (10%); rhinitis (6%); bronchospasm (5%); apnea (1%); lung edema, pulmonary embolus (less than 1%).

Miscellaneous

Asthenia (43%); infection (29%); chills (24%); fever (17%); abdominal pain (16%); pain (13%); allergic reactions, secondary malignancies (2%); tumor pain (1%); hematemesis (less than 1%).

Precautions

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Biodistribution

Do not administer Y-90 ibritumomab tiuxetan to patients with altered biodistribution of In-111 ibritumomab tiuxetan

Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, may occur.

Infections

Because this product contains albumin, a derivative of human blood, there is a risk of transmitting infectious agents (eg, viruses), including Creutzfeldt-Jakob disease.

Radionuclide precautions

The ibritumomab tiuxetan kit is not radioactive. However, during and after radiolabeling ibritumomab tiuxetan with In-111 or Y-90, take care to minimize radiation exposure of patients and medical personnel.

Secondary malignancies

Acute myelogenous leukemia and myelodysplastic syndrome have been reported following the ibritumomab tiuxetan therapeutic regimen.

Overdosage

Symptoms

Hematologic toxicity.

Patient Information

• Explain name, dose, action, and potential adverse reactions of drug.
• Obtain patient history, including drug history and any known allergies.
• Advise women to avoid becoming pregnant, and to use effective contraceptive methods during treatment and for up to 12 mo following the ibritumomab tiuxetan therapeutic regimen.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Caution patient to not take any prescription or OTC medications, herbal preparations, or dietary supplements unless advised by health care provider.
• Advise patient that follow-up visits may be necessary and to keep appointments.