Dosing & Administration

ZEVALIN treatment is administered on an outpatient basis within 9 days. The regimen consists of 3 steps:

• Day 1: Premedication + rituximab
• Day 7 or 8 or 9: Premedication + rituximab + ZEVALIN¹

 

 

Patient Selection

Rituximab, a CD20-directed monoclonal antibody, is included in the ZEVALIN regimen to deplete levels of circulating B cells, increasing the opportunity for ZEVALIN to reach the tumor site. The dose of rituximab used as part of the ZEVALIN regimen is 250 mg/m². Note that this dose is different than the dose of rituximab used as a single agent to treat NHL.

The dose of ZEVALIN administered is based on the patient’s platelet count and actual body weight. ZEVALIN should be administered as an intravenous injection over a period of 10 minutes at the recommended dose.¹

• If platelet counts are ≥ 150,000/mm³: ZEVALIN should be administered at 0.4 mCi/kg (14.8 MBq/kg) actual body weight¹
• In relapsed or refractory patients with platelets count between 100,000 and 149,000/mm³: ZEVALIN should be administered at 0.3 mCi/kg (11.1 MBq/kg) actual body weight¹
• The total dose of ZEVALIN administered should not exceed 32 mCi (1184 MBq), regardless of the patient’s body weight¹
• The ZEVALIN regimen is used in adults. The safety and effectiveness of ZEVALIN have not been established in pediatric patients¹

ZEVALIN is available by prescription only.

The ZEVALIN regimen is typically administered as follows

Day 1

• Premedication with acetaminophen 650 mg orally and diphenhydramine 50 mg orally prior to the rituximab infusion¹
• Administer rituximab

Rituximab 250 mg/m² administered by IV infusion at an initial rate of 50 mg/hr¹

In the absence of infusion reactions, escalate the infusion rate in 50 mg/hr increments every 30 minutes to a maximum of 400 mg/hr. Do not mix or dilute rituximab with other drugs¹

• Immediately stop the rituximab infusion for serious infusion reactions and discontinue the ZEVALIN regimen¹
• Temporarily slow or interrupt the rituximab infusion for less severe infusion reactions. If symptoms improve, continue the infusion at one-half the previous rate¹
• This infusion may take several hours to complete¹

Day 7, 8, or 9

• Premedication with acetaminophen 650 mg orally and diphenhydramine 50 mg orally prior to the rituximab infusion¹
• Administer rituximab

Rituximab 250 mg/m² administered by IV infusion at an initial rate of 100 mg/hr¹

Increase the rate by 100 mg/hr increments at 30 minute intervals to a maximum of 400 mg/hr, as tolerated¹

If infusion reactions occurred during rituximab infusion on Day 1 of treatment, administer rituximab at an initial rate of 50 mg/hr and escalate the infusion rate in 50 mg/hr increments every 30 minutes to a maximum of 400 mg/hr¹

• Within 4 hours of completing the rituximab infusion, the dose of ZEVALIN, which is based on the patient’s platelet count and actual body weight, should be administered by a 10-minute IV injection. Use a 0.22 micron low-protein-binding in-line filter between the syringe and the infusion port. Flush the line with at least 10 ml of normal saline after injection¹
  • If platelet counts are ≥ 150,000/mm³: ZEVALIN should be administered at 0.4 mCi/kg(14.8 MBq/kg) actual body weight¹
  • In relapsed or refractory patients with platelet counts 100,000-149,000/mm³: ZEVALIN should be administered at 0.3 mCi/kg (11.1 MBq/kg) actual body weight¹
  • The total dose of ZEVALIN administered should not exceed 32 mCi (1184 MBq), regardless of the patient’s body weight¹
  • Monitor patients closely for evidence of extravasation during injection of ZEVALIN. Immediately stop infusion and restart in another limb if any signs or symptoms of extravasation occur¹

Following ZEVALIN Administration

• Complete blood counts (CBC) and platelet counts should be monitored weekly for cytopenias and their complications (e.g. febrile neutropenia, hemorrhage) for up to 3 months following ZEVALIN Administration until levels recover or as clinically indicated. ¹

 

References

1. ZEVALIN [package insert]. Irvine, CA: Spectrum Pharmaceuticals, Inc.; 2011.
2. Rituxan (rituximab) US Prescribing Information. South San Francisco, CA: Genentech, Inc.; 2009.



 

View Indications and Important Safety Information

ZEVALIN^® (ibritumomab tiuxetan) is a CD20-directed radiotherapeutic antibody administered as part of the ZEVALIN therapeutic regimen indicated for the treatment of patients with:

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

WARNING: SERIOUS INFUSION REACTIONS, PROLONGED AND SEVERE CYTOPENIAS, and SEVERE CUTANEOUS AND MUCOCUTANEOUS REACTIONS Serious Infusion Reactions: Deaths have occurred within 24 hours of rituximab infusion, an essential component of the ZEVALIN 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 ZEVALIN infusions in patients who develop severe infusion reactions. Prolonged and Severe Cytopenias: Y-90 ZEVALIN administration results in severe and prolonged cytopenias in most patients. Do not administer Y-90 ZEVALIN to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve. Severe Cutaneous and Mucocutaneous Reactions: 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. Dosing: The dose of Y-90 ZEVALIN should not exceed 32.0 mCi (1184 MBq).

ADDITIONAL IMPORTANT SAFETY INFORMATION

Leukemia and Myelodysplastic Syndrome: Among 204 patients receiving Y-90-ZEVALIN following first-line chemotherapy, two patients (1%) were diagnosed with AML within 3 years of receiving ZEVALIN.

Myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML) were reported in 5.2% (11/211) of patients with relapsed or refractory NHL enrolled in clinical studies and 1.5% (8/535) of patients included in the expanded-access trial, with median follow-up of 6.5 and 4.4 years, respectively. Among the 19 reported cases, the median time to diagnosis of MDS or AML was 1.9 years following treatment with the ZEVALIN therapeutic regimen; however, the cumulative incidence continues to increase.

Embryo-fetal Toxicity: May cause fetal harm if given during pregnancy.

Extravasation: Monitor for extravasation and terminate infusion if it occurs. Resume infusion in another limb.

Immunization: Do not administer live viral vaccines to patients who recently received ZEVALIN.

Laboratory Monitoring: Obtain complete blood counts (CBC) and platelet counts at least weekly.

Radionuclide Precautions: During and after radiolabeling ZEVALIN with Y-90, minimize radiation exposure to patients and to medical personnel, consistent with institutional good radiation safety practices and patient management procedures.

Creutzfeldt-Jakob Disease (CJD): The ZEVALIN therapeutic regimen contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, ZEVALIN carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of CJD also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

Impairment of Fertility: There is a potential risk that the ZEVALIN therapeutic regimen could cause toxic effects on the male and female gonads. Effective contraceptive methods should be used during treatment and for up to 12 months following the ZEVALIN therapeutic regimen.

Nursing Mothers: Patients should be advised to discontinue nursing during and after ZEVALIN treatment.

Adverse Reactions: The most common adverse reactions of ZEVALIN are cytopenias, fatigue, abdominal pain, nausea, nasopharyngitis, asthenia, diarrhea, cough, and pyrexia. Common adverse reactions (≥40%) in clinical trials were: neutropenia, leukopenia, thrombocytopenia, anemia, infection, asthenia, musculoskeletal symptoms, and gastrointestinal symptoms. The most serious adverse reactions of ZEVALIN are prolonged and severe cytopenias (thrombocytopenia, anemia, lymphopenia, neutropenia) and secondary malignancies.

When administered following first-line chemotherapy, grade 3/4 adverse reactions of ZEVALIN include prolonged and severe cytopenias (thrombocytopenia [51%], neutropenia [41%], leukopenia [36%], lymphopenia [18%], and anemia [5%]) and secondary malignancies. Cytopenias were more severe and more prolonged among eleven (5%) patients who received ZEVALIN after first-line fludarabine or a fludarabine-containing chemotherapy regimen as compared to patients receiving non–fludarabine-containing regimens. Grade 3/4 infections occurred in 8% of ZEVALIN-treated patients and in 2% of controls and included neutropenic sepsis (1%), bronchitis, catheter sepsis, diverticulitis, herpes zoster, influenza, lower respiratory tract infection, sinusitis, and upper respiratory tract infection.

Grade 3/4 adverse reactions of ZEVALIN in relapsed or refractory NHL patients include prolonged and severe cytopenias (thrombocytopenia [63%], neutropenia [60%], anemia [17%], and ecchymosis [<1%]) and secondary malignancies. Serious infections occurred in 3% of patients (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, and upper respiratory tract infection). Life-threatening infections were reported in 2% of patients (sepsis, empyema, pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis).

Please click here to read full Prescribing Information, including BOXED WARNINGS, for ZEVALIN. Because the ZEVALIN therapeutic regimen includes the use of rituximab, please also consult prescribing information for rituximab.