ibritumomab

High Alert

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/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 ⬆ ⬇

ROUTE	B cell depletion	B cell recovery	B cells in normal range
IV	4 wk	2 wk	9 mo

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to ibritumomab, indium-111, yttrium-90, or murine proteins;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Thrombocytopenia (step 2 dose of yttrium-90 ibritumomab should be ↓);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: ecchymoses, ERYTHEMA MULTIFORME, pruritus, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

EENT: rhinitis

GI: abdominal pain, anorexia, diarrhea, nausea, vomiting

GU: ↓fertility

Hemat: anemia, leukopenia, thrombocytopenia

MS: arthralgia

Neuro: anxiety, dizziness

Resp: cough, dyspnea, bronchospasm

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS) , INFECTION, INFUSION REACTIONS, SECONDARY MALIGNANCIES

Interactions ⬆ ⬇

Drug-drug:

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 after treatment.

Route/Dosage ⬆ ⬇

Day 1

IV (Adults ): Administer rituximab 250 mg/m².

Days 7, 8, or 9

IV (Adults ): Administer rituximab 250 mg/m²; within 4 hr after rituximab infusion, administer Y-90 ibritumomab at dose based on platelet level: If platelets ≥150,000/mm³: Administer 0.4 mCi/kg (14.8 MBq per kg) Y-90 ibritumomab; If platelets 100,000–149,000/mm³: Administer 0.3 mCi/kg (11.1 MBq per kg) Y-90 ibritumomab.

Availability ⬆ ⬇

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)

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, ventricular fibrillation, cardiogenic shock). Temporarily slow or interrupt rituximab infusion for less severe infusion reactions. If severe reaction occurs, discontinue infusion.
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. SJS or TEN may develop. Treat symptomatically; may occur from early therapy to 4 mo after therapy.

Lab Test Considerations:

Obtain a negative pregnancy test before starting therapy. 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.

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.

IV 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 hr after rituximab infusion.
Rate: Inject over 10 min.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

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; purpura; 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.
Rep: Caution female patients of reproductive potential and male patients with female partners of reproductive potential 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇