Ibritumomab Tiuxetan

(ib ri TYOO mo mab tye UX e tan)

B cell recovery begins in ~12 weeks; generally in normal range within 9 months

Half-Life Elimination

Y-90 ibritumomab: 30 hours; Yttrium-90 decays with a physical half-life of 64 hours

There are no contraindications listed within the manufacturer's labeling.

Note: Premedicate with oral acetaminophen 650 mg and oral diphenhydramine 50 mg prior to each rituximab infusion. Allow at least 6 weeks, but no more than 12 weeks following first-line chemotherapy before treatment initiation; platelets should recover to ≥150,000/mm3 prior to initiation of treatment regimen.

Non-Hodgkin lymphoma: Ibritumomab is administered only as part of the Zevalin therapeutic regimen (a combined treatment regimen with rituximab). The regimen consists of two steps:

Day 1:

Rituximab: IV: 250 mg/m2 at an initial rate of 50 mg/hour. If hypersensitivity or infusion-related events do not occur, increase infusion in increments of 50 mg/hour every 30 minutes, to a maximum of 400 mg/hour. Stop rituximab and discontinue regimen for severe infusion reaction. For less severe infusion reactions, temporarily slow or interrupt; the infusion may be resumed at one-half the previous rate upon improvement of symptoms.

Day 7, 8, or 9 of treatment:

Rituximab: IV: 250 mg/m2 at an initial rate of 100 mg/hour (50 mg/hour if infusion-related events occurred with the day 1 infusion). If hypersensitivity or infusion-related events do not occur, increase infusion in increments of 100 mg/hour every 30 minutes, to a maximum of 400 mg/hour, as tolerated (increase in 50 mg/hour increments every 30 minutes if initial infusion rate was 50 mg/hour).

Y-90 ibritumomab (within 4 hours after completion of the rituximab infusion): IV:

Platelet count ≥150,000 cells/mm3: 0.4 mCi/kg (14.8 MBq/kg) actual body weight over 10 minutes; maximum dose: 32 mCi (1184 MBq)

Platelet count between 100,000 to 149,000 cells/mm3 (in relapsed or refractory patients): 0.3 mCi/kg (11.1 MBq/kg) actual body weight over 10 minutes; maximum dose: 32 mCi (1184 MBq)

Platelet count <100,000 cells/mm3: Do not administer

Maximum dose: The prescribed, measured, and administered dose of Y-90 ibritumomab must not exceed 32 mCi (1184 MBq), regardless of the patient's body weight

Refer to adult dosing.

Radiopharmaceutical; use appropriate precautions for handling and disposal. To prepare radiolabeled injection and determine radiochemical purity, follow detailed preparation guidelines provided by manufacturer. Use appropriate shielding during and after radiolabeling.

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

Y-90 ibritumomab tiuxetan administration results in severe and prolonged cytopenias in most patients. Do not administer the ibritumomab tiuxetan therapeutic regimen to patients with 25% or greater lymphoma marrow involvement and/or impaired bone marrow reserve.

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

The dose of Y-90 ibritumomab tiuxetan should not exceed 32 mCi (1,184 MBq).

Animal reproduction studies have not been conducted. Based on the radioactivity, Y-90 ibritumomab may cause fetal harm if administered during pregnancy. IgG molecules are known to cross the placenta. Women of reproductive potential should avoid becoming pregnant during treatment with ibritumomab. Females of reproductive potential and males with female partners of reproductive potential should use effective contraception for at least 12 months following treatment. The effect on future fertility is unknown.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Feeling tired or weak.
• Nose and throat irritation.
• Loose stools (diarrhea).
• Upset stomach.
• Belly pain.
• Muscle pain.
• Not hungry.
• Night sweats.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.