ibritumomab

ibritumomab

(i-bri-too-mo-mab) ,

Zevalin

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: monoclonal antibodies
Pregnancy Category: D

Indications

Relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (including rituximab-resistant).Previously untreated follicular non-Hodgkin's lymphoma in patients who achieve a partial or complete response to first-line chemotherapy.

Action

Ibritumomab is a monoclonal antibody linked to a radioisotope that targets white blood cells, including malignant ones. Used in combination with rituxumab as part of a two-step process using indium-111 (step 1) and yttrium-90 (step 2) ibritumomab.

Therapeutic effects

Decreased spread of lymphoma.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Distributes to lymphoid tissue in bone marrow, lymph nodes, thymus, spleen, tonsils, and lymphoid nodules in the intestinal tract.
Metabolism and Excretion: Over 7 days, 7.2% of injected radioactivity was excreted in urine.
Half-life: Mean half-life of yttrium-90–ibritumomab activity in blood is 30 hr.

Time/action profile

ROUTEB cell depletionB cell recoveryB cells in normal range
IV4 wk2 wk9 mo

Contraindications/Precautions

Contraindicated in: Hypersensitivity to ibritumomab, indium-111, yttrium-90, or murine proteins; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: Thrombocytopenia (step 2 dose of yttrium-90 ibritumomab should be ↓); Pediatric: Children (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • anxiety (most frequent)
  • dizziness (most frequent)

Ear, Eye, Nose, Throat

  • rhinitis

Respiratory

  • cough (most frequent)
  • dyspnea (most frequent)
  • bronchospasm

Gastrointestinal

  • abdominal pain
  • anorexia
  • diarrhea
  • nausea
  • vomiting

Dermatologic

  • ecchymoses (most frequent)
  • pruritis

Hematologic

  • leukopenia
  • thrombocytopenia
  • anemia (most frequent)

Musculoskeletal

  • arthralgia (most frequent)

Miscellaneous

  • infections (life-threatening)
  • infusion reactions (life-threatening)
  • allergic reactions including anaphylaxis (life-threatening)
  • secondary malignancies (life-threatening)

Interactions

Drug-Drug interaction

May ↓ antibody response to, and ↑ risk of adverse reactions from, live-virus vaccines.↑ risk of bleeding with anticoagulants, antiplatelet agents, and other agents that may affect hemostasis.Growth factor should be avoided for 2 wk before and two wk following treatment.

Route/Dosage

Step 1

Intravenous (Adults) 5.0 mCi (1.6 mg total antibody dose) of indium-111 ibritumomab, preceded by rituximab 250 mg/m2 within 4 hr.

Step 2

Intravenous (Adults) 7–9 days after Step 1—0.4 mCi/kg of yttrium-90 ibritumomab, preceded by rituximab 250 mg/m2 within 4 hr.

Availability

Indium-111 (In-111) Zevalin kit: contains one 2–ml vial of 3.2 mg ibritumomab in solution, one 50 mM sodium acetate vial, one formulation buffer vial, and one empty reaction vial with four identification labels (indium-111 is ordered separately)
Yttrium-90 (Y-90) Zevalin kit: contains one 2-ml vial of 3.2 mg ibritumomab in solution, one 50 mM sodium acetate vial, one formulation buffer vial, and one empty reaction vial with four identification labels (yttrium-90 is shipped directly)

Nursing implications

Nursing assessment

  • Assess for signs of infusion reaction with rituximab/ibritumomab infusion usually seen within 30–120 min following rituximab infusion (urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, MI, VFib, cardiogenic shock). Temporarily slow or interrupt rituximab infusion for less severe infusion reactions. If severe reaction occurs, infusion should be discontinued.
  • Monitor patient for neutropenia (fever) and thrombocytopenia (hemorrhage) during and for 3 mo following treatment.
  • Biodistribution of indium-111 Zevalin should be assessed at 2–24 hr and 48–72 hr after injection.
  • Assess patient for skin rash frequently during therapy. Discontinue ibritumomab at first sign of rash; may be life-threatening. Stevens-Johnson syndrome or toxic epidermal necrolysis may develop. Treat symptomatically; may occur from early therapy to 4 mo after therapy.
  • Lab Test Considerations: Monitor CBC and platelet counts prior to administration, weekly during therapy, and until counts recover. Monitor more frequently in patients with severe thrombocytopenia. Dose of ibritumomab is based on platelet count (See Route and Dosage). Do not administer to patients with platelet count <100,000 cells/mm3 or neutrophil count <1500 cells/mm3. May cause thrombocytopenia and neutropenia. Nadir occurs in 7–9 wk with a duration of 22–35 days.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Ibritumomab should be administered only by health care professionals trained or experienced in safe use and handling of radiopharmaceuticals and in facilities where immediate access to resuscitative measures is available.
    • Avoid extravasation. Establish a free-flowing IV line prior to administration. Monitor closely for extravasation; if signs of extravasation occur, discontinue injection immediately and restart in another vein.
  • Intravenous Administration
  • Premedicate with acetaminophen 650 mg PO and diphenhydramine 50 mg PO prior to rituximab infusion.
  • Waterproof gloves should be worn during medication preparation and determination of purity. Radiolabeling and a syringe shield should be used during administration.
    • Administer ibritumomab within 4 hrs after rituximab infusion.
  • Rate: Administer over 10 min.

Patient/Family Teaching

  • Inform patient of the purpose and procedure for ibritumomab.
  • Instruct patient to notify health care professional if rash; fever; chills; sore throat; signs of infection; bleeding gums; bruising; prupura; petechiae; pallor; weakness; fatigue; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patients should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs; may increase GI irritation.
  • Caution patient not to receive live vaccines during and for 12 mo following therapy.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Caution female patients to use contraception during and for at least 12 mo following therapy and to avoid breastfeeding. Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Decrease in the spread of lymphoma.
References in periodicals archive ?
and its affiliates for which CASI has exclusive rights to the greater China market, consisting of EVOMELA[R] (Melphalan for Injection), ZEVALIN[R](Ibritumomab Tiuxetan) and MARQIBO[R] (Vincristine Sulfate Liposome Injection); and (iv) a portfolio of FDA-approved and pending abbreviated new drug applications (ANDAs), including entecavir and tenofovir disoproxil fumarate (TDF) indicated for the treatment of hepatitis B virus.
and its affiliates for which CASI has exclusive rights to the greater China market, consisting of EVOMELA (Melphalan for Injection), ZEVALIN (Ibritumomab Tiuxetan) and MARQIBO (Vincristine Sulfate Liposome Injection) and (iv) a portfolio of FDA-approved and pending abbreviated new drug applications (ANDAs), including entecavir and tenofovir disoproxil fumarate (TDF) indicated for the treatment of hepatitis B virus.
CASI Pharmaceuticals (CASI) announced that the National Medical Products Administration has approved the company's Clinical Trial Application to allow for a confirmatory clinical trial to evaluate the efficacy and safety of ibritumomab tiuxetan injection (ZEVALIN).
Under the deal, Acrotech will acquire products including Fusilev (levoleucovorin), Folotyn (pralatrexate injection), Zevalin (ibritumomab tiuxetan), Marqibo (vinCRIStine sulfate Liposome injection), Beleodaq (belinostat) for injection, Evomela (melphalan) for injection and Khapzory (levoleucovorin).
Under the sale, the seven US FDA-approved hematology/oncology products include: FUSILEV (levoleucovorin), FOLOTYN (pralatrexate injection), ZEVALIN (ibritumomab tiuxetan), MARQIBO (vinCRIStine sulfate LIPOSOME injection), BELEODAQ (belinostat) for injection, EVOMELA (melphalan) for injection, and KHAPZORY (levoleucovorin).
Joyce, "Zevalin[TM]: 90ytrium labeled anti-CD20 (Ibritumomab tiuxe tan), a new treatment for nonHodgkin's lymphoma, " Current Pharmaceutical Biotechnology, vol.
Some examples of radiolabeled antibodies for RIT are [sup.90]Y-murine anti-CD20 antibody; ibritumomab, approved for clinical practice for the treatment of lymphoma some years ago [4]; [sup.131]I-tositumomab, which recognizes and binds to the B1 (CD20) antigen which is found specifically on B lymphocytes [5] and has been used to treat chronic lymphocytic leukemia or small lymphocytic lymphoma in first remission; and [sup.177]Lu-girentuximab, used in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) [6].
I am very proud of these accomplishments, including, TRISENOX (arsenic trioxide) now the standard of care in treating patients with a rare form of leukemia; expanding the indication for ZEVALIN (ibritumomab tiuxetan), the first approved radio-immunotherapy for patients with a chronic form of lymphoma; and PIXUVRI (pixantrone), the first and only treatment approved for patients with relapsed aggressive B-cell non-Hodgkin lymphoma.
Bu amacla 90Y ibritumomab tiuxetan "Zevalin" ve [sup.13]1I tositumomab "Bexxar" kullanilmaktadir.
Ibritumomab. Ibritumomab is a murine IgG-1 kappa anti-CD20 antibody that is conjugated to yttrium-90 (pure beta emitter) or indium-111 (gamma emitter) in the presence of chelate tiuxetan (Mx-DTPA) [7, 8].
Each preparation kit consisted of 3 vials containing ibritumomab tiuxetan, sodium acetate, and buffer solution, as well as an empty reaction vial.
(11) Currently, 2 radiolabelled antibodies are available for treatment of follicular non-Hodgkin's lymphoma, Y-90 ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar).