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Zevalin

Last reviewed on RxList: 8/7/2020
Zevalin Side Effects Center

What Is Zevalin?

Zevalin (ibritumomab tiuxetan) is a protein that targets white blood cells in the body used in combination with other medicines to treat non-Hodgkin's lymphoma.

What Are Side Effects of Zevalin?

Common side effects of Zevalin include:

Dosage for Zevalin

A physician will determine the dosage of Zevalin and the dosing schedule.

What Drugs, Substances, or Supplements Interact with Zevalin?

Zevalin may interact with any type of blood thinner or medication use to prevent blood clots, such as: warfarin, alteplase, anistreplase, clopidogrel, dipyridamole, streptokinase, sulfinpyrazone, ticlopidine, or urokinase. Tell your doctor all medications and supplements you use.

Zevalin During Pregnancy and Breastfeeding

Zevalin is not recommended for use during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor. It is unknown if this drug passes into breast milk. Because of the possible risk to the infant, breastfeeding while using this drug is not recommended.

Additional Information

Our Zevalin (ibritumomab tiuxetan) Drug Center provides a comprehensive view of available drug information as well as related drugs, user reviews, supplements, and diseases and conditions articles.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Zevalin Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Life-threatening reactions may occur during the injection or within 24 hours afterward. Tell your caregivers or seek medical attention if you feel light-headed or short of breath, or if you have chest tightness or pain spreading to your jaw or shoulder.

Serious and sometimes fatal infections or skin reactions may occur during treatment with ibritumomab, and up to 4 months afterward. Call your doctor right away if you have:

  • redness, ulcers, or skin changes where the medicine was injected;
  • easy bruising, unusual bleeding, purple or red spots under your skin;
  • unusual weakness or tiredness;
  • low red blood cells (anemia)--pale skin, weakness, cold hands and feet; or
  • low white blood cell counts--fever, mouth sores, skin sores, sore throat, cough, trouble breathing.

Common side effects may include:

  • nausea, stomach pain, diarrhea;
  • fever, cough;
  • stuffy nose, sore throat, sinus pain; or
  • feeling weak or tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zevalin (Ibritumomab Tiuxetan)

Zevalin Professional Information

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the label:

  • Serious Infusion Reactions [see BOXED WARNING and WARNINGS AND PRECAUTIONS].
  • Prolonged and Severe Cytopenias [see BOXED WARNING and WARNINGS AND PRECAUTIONS].
  • Severe Cutaneous and Mucocutaneous Reactions [see BOXED WARNING and WARNINGS AND PRECAUTIONS].
  • Leukemia and Myelodysplastic Syndrome [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The reported safety data reflects exposure to Zevalin in 349 patients with relapsed or refractory, low-grade, follicular or transformed NHL across 5 trials (4 single arm and 1 randomized) and in 206 patients with previously untreated follicular NHL in a randomized trial (FIT study) who received any portion of the Zevalin therapeutic regimen. The safety data reflect exposure to Zevalin in 270 patients with relapsed or refractory NHL with platelet counts ≥150,000/ mm3 who received 0.4 mCi/kg (14.8 MBq/kg) of Y-90 Zevalin (Group 1 in Table 4), 65 patients with relapsed or refractory NHL with platelet counts of ≥ 100,000 but ≤ 149,000 /mm3 who received 0.3 mCi/kg (11.1 MBq/kg) of Y-90 Zevalin (Group 2 in Table 4), and 204 patients with previously untreated NHL with platelet counts ≥150,000/ mm who received 0.4 mCi/kg (14.8 MBq/kg) of Y-90 Zevalin; all patients received a single course of Zevalin.

The most common adverse reactions of Zevalin are cytopenias, fatigue, nasopharyngitis, nausea, abdominal pain, asthenia, cough, diarrhea, and pyrexia.

The most serious adverse reactions of Zevalin are prolonged and severe cytopenias (thrombocytopenia, anemia, lymphopenia, neutropenia) and secondary malignancies.

Because the Zevalin therapeutic regimen includes the use of rituximab, see prescribing information for rituximab.

Table 2 displays selected adverse reaction incidence rates in patients who received any portion of the Zevalin therapeutic regimen (n=206) or no further therapy (n=203) following first-line chemotherapy (FIT study).

Table 2. Per-Patient Incidence (%) of Selected* Adverse Reactions Occurring in ≥ 5% of Patients with Previously Untreated Follicular NHL Treated with the Zevalin Therapeutic Regimen

Zevalin (n=206)Observation (n=203)
All GradesGrade 3-4All Grades Grade 3-4
%%%%
Gastrointestinal Disorders
Abdominal pain17213<1
Diarrhea11030
Nausea18020
Body as a Whole
Asthenia1518<1
Fatigue33190
Influenza-like illness8030
Pyrexia10340
Musculoskeletal
Myalgia9030
Metabolism
Anorexia8020
Respiratory, Thoracic & Media
Cough11<150
Pharyngolaryngeal pain7020
Epistaxis52<10
Nervous System
Dizziness7020
Vascular
Hypertension732<1
Skin & Subcutaneous
Night sweats8020
Petechiae8200
Pruritus7010
Rash70<10
Infections & Infestations
Bronchitis8030
Nasopharyngitis190100
Rhinitis8020
Sinusitis7<1<10
Urinary tract infection7<130
Blood and Lymphatic System
Thrombocytopenia625110
Neutropenia454132
Anemia22540
Leukopenia433641
Lymphopenia261895
* Between-group difference of ≥5%
NCI CTCAE version 2.0

Table 3 shows hematologic toxicities in 349 Zevalin-treated patients with relapsed or refractory, low-grade, follicular or transformed B-cell NHL. Grade 2-4 hematologic toxicity occurred in 86% of Zevalin-treated patients.

Table 3. Per-Patient Incidence (%) of Hematologic Adverse Reactions in Patients with Relapsed or Refractory Lowgrade, Follicular or Transformed B-cell NHL* (N = 349

All Grades
%
Grade 3-4
%
Thrombocytopenia9563
Neutropenia7760
Anemia6117
Ecchymosis7<1
* Occurring within the 12 weeks following the first rituximab infusion of the Zevalin therapeutic regimen

Prolonged And Severe Cytopenias

Patients in clinical studies were not permitted to receive hematopoietic growth factors beginning 2 weeks prior to administration of the Zevalin therapeutic regimen.

The incidence and duration of severe hematologic toxicity in previously treated NHL patients (N=335) and in previously untreated patients (FIT study) receiving Y-90 Zevalin are shown in Table 4.

Table 4. Severe Hematologic Toxicity in Patients Receiving Zevalin

Baseline Platelet CountGroup 1
(n=270)

150,000/mm3
Group 2
(n=65 )
≥ 100,000 but ≤ 149,000/mm3
FIT study
(n=204)

150,000/mm3
Y-90 Zevalin Dose0.4 mCi/kg
(14.8 MBq/kg)
0.3 mCi/kg
(11.1 MBq/kg)
0.4 mCi/kg
(14.8 MBq/kg)
ANC
  Median nadir ( per mm3)800600721
  Per Patient Incidence
ANC <1000/mm3
57%74%65%
  Per Patient Incidence
ANC <500/mm3
30%35%26%
Median Duration (Days)* ANC <1000/mm3222929
Median Time to Recovery121315
Platelets
Median nadir (per mm3)41,00024,00042,000
Per Patient Incidence
Platelets <50,000/mm3
61%78%61%
Per Patient Incidence
Platelets <10,000/mm3
10%14%4%
Median Duration (Days)Platelets <50,000/mm3243526
Median Time to Recovery131414
* Day from last ANC ≥1000/mm3 to first ANC ≥1000/mm3 following nadir, censored at next treatment or death
Day from nadir to first count at level of Grade 1 toxicity or baseline
Day from last platelet count ≥50,000/mm3 to day of first platelet count ≥50,000/mm3 following nadir, censored at next treatment or death

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. Among these eleven patients, the median platelet nadir was 13,000/mm with a median duration of platelets below 50,000/mm3 of 56 days and the median time for platelet recovery from nadir to Grade 1 toxicity or baseline was 35 days. The median ANC was 355/mm3, with a median duration of ANC below 1,000/mm of 37 days and the median time for ANC recovery from nadir to Grade 1 toxicity or baseline was 20 days.

The median time to cytopenia was similar across patients with relapsed/refractory NHL and those completing first-line chemotherapy, with median ANC nadir at 61-62 days, platelet nadir at 49-53 days, and hemoglobin nadir at 68-69 days after Y-90-Zevalin administration.

Information on hematopoietic growth factor use and platelet transfusions is based on 211 patients with relapsed/refractory NHL and 206 patients following firstline chemotherapy. Filgrastim was given to 13% of patients and erythropoietin to 8% with relapsed or refractory disease; 14% of patients receiving Zevalin following first-line chemotherapy received granulocyte-colony stimulating factors and 5% received erythopoiesis-stimulating agents. Platelet transfusions were given to approximately 22% of all Zevalin-treated patients. Red blood cell transfusions were given to 20% of patients with relapsed or refractory NHL and 2% of patients receiving Zevalin following first-line chemotherapy.

Infections

In relapsed or refractory NHL patients, infections occurred in 29% of 349 patients during the first 3 months after initiating the Zevalin therapeutic regimen and 3% developed serious infections (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, and upper respiratory tract infection). Life-threatening infections were reported in 2% (sepsis, empyema, pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis). From 3 months to 4 years after Zevalin treatment, 6% of patients developed infections; 2% were serious (urinary tract infection, bacterial or viral pneumonia, febrile neutropenia, perihilar infiltrate, pericarditis, and intravenous drug-associated viral hepatitis) and 1% were life-threatening infections (bacterial pneumonia, respiratory disease, and sepsis).

When administered following first-line chemotherapy (Table 2), 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.

Leukemia And Myelodysplastic Syndrome

Among 746 patients with relapsed/refractory NHL, 19 (2.6%) patients developed MDS/AML with a median follow-up of 4.4 years. The overall incidence of MDS/AML among the 211 patients included in the clinical studies was 5.2% (11/211), with a median follow-up of 6.5 years and median time to development of MDS/AML of 2.9 years. The cumulative Kaplan-Meier estimated incidence of MDS/secondary leukemia in this patient population was 2.2% at 2 years and 5.9% at 5 years. The incidence of MDS/AML among the 535 patients in the expanded access programs was 1.5% (8/535) with a median follow-up of 4.4 years and median time to development of MDS/AML of 1.5 years. Multiple cytogenetic abnormalities were described, most commonly involving chromosomes 5 and/or 7. The risk of MDS/AML was not associated with the number of prior treatments (0-1 versus 2-10).

Among 204 patients receiving Y-90-Zevalin following first-line treatment, 7 (3%) patients developed MDS/AML between approximately 2 to 7 years after Zevalin administration [see WARNINGS AND PRECAUTIONS].

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of the Zevalin therapeutic regimen in hematologic malignancies. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to the Zevalin therapeutic regimen.

  • Cutaneous and mucocutaneous reactions: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous dermatitis, and exfoliative dermatitis [see BOXED WARNING and WARNINGS AND PRECAUTIONS].
  • Infusion site erythema and ulceration following extravasation [see WARNINGS AND PRECAUTIONS].
  • Radiation injury in tissues near areas of lymphomatous involvement within a month of Zevalin administration.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparisons of the incidence of antibodies to the Zevalin therapeutic regimen in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

HAMA and HACA response data on 446 patients from 8 clinical studies conducted over a 10-year time period are available. Overall, 11/446 (2.5%) had evidence of either HAMA formation (N=8) or HACA formation (N=4). Six of these patients developed HAMA/HACA after treatment with Zevalin and 5 were HAMA/HACA positive at baseline. Of the 6 who were HAMA/HACA positive, only one was positive for both. Furthermore, in 6 of the 11 patients, the HAMA/HACA reverted to negative within 2 weeks to 3 months. No patients had increasing levels of HAMA/HACA at the end of the studies.

Only 6/446 patients (1.3%) had developed evidence of antibody formation after treatment with Zevalin, and of these, many either reverted to negative or decreased over time. This data demonstrates that HAMA/HACA develop infrequently, are typically transient, and do not increase with time.

Read the entire FDA prescribing information for Zevalin (Ibritumomab Tiuxetan)

Related Resources for Zevalin

Read the Zevalin User Reviews »

© Zevalin Patient Information is supplied by Cerner Multum, Inc. and Zevalin Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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