Ibritumomab Tiuxetan

Trade Names:Zevalin- Injection, solution 3.2 mg

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 (NHL).

Pharmacokinetics

Absorption

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

Elimination

The mean effective half-life for yttrium-90 (Y-90) activity in the blood is 30 h. 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 healthy range (32 to 341 cells/mm ³ ) by 9 mo after treatment.

Indications and Usage

Treatment of relapsed or refractory low-grade or follicular B-cell NHL; treatment of previously untreated follicular NHL in patients who achieve a partial or complete response to first-line chemotherapy.

Contraindications

None well documented.

Dosage and Administration

IV The therapeutic regimen consists of 2 steps. Step 1 includes a single infusion of rituximab 250 mg/m ² at a rate of 50 mg/h. Escalate the infusion in 50 mg/h increments every 30 min to a max of 400 mg/h. Within 4 h following completion of the rituximab infusion, administer 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 at a rate of 100 mg/h. Escalate the infusion in 100 mg/h increments at 30-min intervals to a max of 400 mg/h. Within 4 h following completion of the rituximab infusion, administer Y-90 ibritumomab tiuxetan 0.4 mCi/kg as a 10-min IV push (max, 32 mCi (1,184 MBq). 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 . Do not administer to patients with platelets less than 100,000 cells/mm ³ .

General Advice

• For IV administration only.
• Premedicate with acetaminophen 650 mg and diphenhydramine 50 mg prior to each infusion of rituximab.
• Immediately stop the rituximab infusion for serious infusion reactions and discontinue the ibritumomab tiuxetan therapeutic regimen. Temporarily slow or interrupt the rituximab infusion for less severe infusion reactions. If symptoms improve, continue the infusion at half the previous dose.
• Inject In-111 or Y-90 ibritumomab tiuxetan within 4 h following completion of the rituximab dose.
• Prior to step 2, verify that biodistribution is present 48 to 72 hours after In-111 ibritumomab tiuxetan administration; do not proceed if biodistribution is not acceptable.
• 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.
• Do not mix or dilute rituximab with other drugs.
• 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. Administer In-111 ibritumomab tiuxetan within 12 h of radiolabeling. Administer Y-90 ibritumomab tiuxetan within 8 h of radiolabeling.

Drug Interactions

Risk of bleeding or hemorrhage, as well as cytopenias, may be increased by concomitant therapy. Avoid coadministration. If coadministered, monitor anticoagulant function and frequently monitor for thrombocytopenia.

May alter the biodistribution pattern by increasing bone marrow uptake of ibritumomab tiuxetan. Reassess biodistribution after correction of underlying factors.

A reduced immune response may occur following administration of live vaccines. Avoid immunization with a live vaccine for 12 mo following ibritumomab therapy.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Fatigue (33%); dizziness (7%).

Dermatologic

Night sweats, petechiae (8%); pruritus, rash (7%); cutaneous and mucocutaneous reactions (postmarketing).

GI

Nausea (18%); abdominal pain (17%); diarrhea (11%); anorexia (8%).

Hematologic-Lymphatic

Thrombocytopenia (95%); platelet count below 50,000 cells/mm ³ (78%); neutropenia (77%); absolute neutrophil count (ANC) below 1,000 cells/mm ³ (74%); anemia (61%); leukopenia (43%); ANC below 500 cells/mm ³ (35%); lymphopenia (26%); platelet count below 10,000 cells/mm ³ (14%).

Local

Infusion-site erythema and ulceration (postmarketing).

Respiratory

Nasopharyngitis (19%); cough (11%); bronchitis, rhinitis (8%); pharyngolaryngeal pain, sinusitis (7%); epistaxis (5%).

Miscellaneous

Infection (29%); asthenia (15%); fever (10%); myalgia (9%); flu-like illness (8%); hypertension, UTI (7%); acute myelogenous leukemia/myelodysplastic syndrome (5%); antibody formation (3%); radiation injury (postmarketing).

Precautions

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

The greater sensitivity of some older individuals cannot be ruled out.

Biodistribution

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

Radiation exposure

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.

Viral disease

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

Overdosage

Symptoms

Hematologic toxicity.

Patient Information

• Advise patients to report any signs or symptoms of cytopenias (eg, bleeding, easy bruising, fatigue, pallor, petechiae or purpura, weakness) or infection (eg, fever).
• Advise patients to seek prompt medication attention for diffuse rash, bullae, or desquamation of the skin or oral mucosa.
• Advise patients that immunization with live viral vaccines is not recommended for 12 mo following ibritumomab tiuxetan therapeutic regimen.
• Advise patients to avoid medications that interfere with platelet function, except as directed by health care provider.
• 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 patients to discontinue breast-feeding during and after ibritumomab tiuxetan treatment.

Copyright © 2009 Wolters Kluwer Health.