Drug information of Ibritumomab tiuxetan


Ibritumomab tiuxetan

Drug group:

Indium or yttrium conjugated murine IgG1 kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Ibritumomab is produced in Chinese hamster ovary cells and is composed of two murine gamma 1 heavy chains of 445 amino acids each and two kappa light chains of 213 amino acids each.

Mechanism of effect

The Fab segment of the antibody targets the CD20 epitope on B-cells, allowing the radioactive yttrium to destroy the cell via production of beta particles.

Pharmacokinetics

Volume of distribution: Binding observed on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, lymphoid follicles of the tonsil, and lymphoid nodules of other organs (e.g., large and small intestines)

Metabolism: Most likely removed by opsonization via the reticuloendothelial system when bound to B cells, or by human antimurine antibody production

Half life: 0.8 hours (mammalian reticulocytes, in vitro)

Clearance: Approximately 7.2% of injected dose of yttrium Y 90 ibritumomab tiuxetan is excreted in urine within 7 days.

Dosage

Adult

Non-Hodgkin Lymphoma

Day 1

  • Initiate the ibritumomab therapeutic regimen following recovery of platelet counts to ≥150,000/mm³ at least 6 weeks, but no more than 12 weeks, following the last dose of first-line chemotherapy
  • Administer acetaminophen 650 mg PO and diphenhydramine 50 mg PO to premedicate prior to rituximab infusion
  • Administer 250 mg/m² IV rituximab infusion at initial rate of 50 mg/hr; may increase rate by 50 mg/hr q30min to 400 mg/hr maximum; discontinue if severe reaction occurs 
  • Administer 5 mCi of In-111 ibritumomab tiuxetan over 10 minutes within 4 hr of rituximab infusion
  • Assess biodistribution by imaging 48-72 hr postadministration

Day 7, 8, or 9

  • Verify that expected biodistribution is present
  • Premedicate with acetaminophen 650 mg PO and diphenhydramine 50 mg PO prior to rituximab infusion
  • Administer 250 mg/m² rituximab at initial rate of 100 mg/hr; increase rate by 100 mg/hr q30min; not to exceed 400 mg/hr 
  • Platelet count >150,000 cells/mm³: Administer 0.4 mCi/kg of Y-90 ibritumomab tiuxetan as 10 minutes IVP within 4 hr of rituximab infusion; not to exceed 32 mCi Y-90 ibritumomab tiuxetan regardless of patient weight
  • Platelet count 100,000-149,000 cells/mm³: Administer 0.3 mCi/kg ibritumomab tiuxetan over 10 min; not to exceed 32 mCi Y-90 ibritumomab tiuxetan regardless of patient weight
  • Platelet count <100,000 cells/mm³: Do not administer

Pediatric

Safety & efficacy not established

Drug contraindications

pregnancy , hypersensitivity to this drug

Hypersensitivity to any component (incl rituximab, yttrium chloride, indium chloride), murine proteins or to another monoclonal antibody
Patients with >25% lymphoma marrow involvement and/or impaired bone marrow reserve
Platelets <100 K/mm³, ANC <1500/mm³
Do NOT administer Y-90 ibritumomab to patients with altered biodistribution as determined by In-111 ibritumomab imaging
Hypocellular bone marrow, failed stem cell collection history, myeloablative therapy history
Pregnancy

Alerts

Patients with prior treatment with murine proteins should be screened for human anti-mouse antibodies

Rituximab dose is lower when coadministered with ibritumomab than when use as a single agent

Effective contraception should be used during and for up to 12 months after treatment

Discontinue if patient develops infusion reaction symptom complex including hypoxia, pulmonary infiltrates, ARDS, MI, ventricular fibrillation, or cardiogenic shock

Risk of severe and prolonged cytopenias; some complicated by hemorrhage and severe infection

Risk of potentially fatal mucocutaneous reactions

Live viral vaccine use, murine protein exposure history

Drug not supplied radiolabeled, radiolabeling must be done in specialized facility

Development of leukemia and myelodysplastic syndrome may occur; monitor patients for hematological toxicity including secondary malignancies

Monitor for extravasation and terminate infusion if it occurs; resume infusion in another limb

Do not administer live viral vaccines to patients who recently received therapy

May cause fetal harm; advise patients of potential risk to a fetus and to use effective contraception

Black Box Warnings

The drug should be administered under the supervision of a cancer chemotherapy physician qualified by training and experienced in the safe use and handling of radionuclides

Fatal infusion reaction symptoms including hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock have occurred within 24 hr of rituximab infusion (~80% occurred in association with the first infusion); discontinue infusions and provide medical treatment to patients who experience infusion reactions

Y-90 ibritumomab tiuxetan administration results in severe and prolonged cytopenias in most patients

Do not administer to patients with greater than or equal to 25% lymphoma marrow involvement and/or impaired bone marrow reserve

Do not exceed absolute maximum allowable dose of 32.0 mCi (1184 MBq) for Y-90 ibritumomab tiuxetan

Do not administer Y-90 ibritumomab tiuxetan to patients with altered biodistribution as determined by imaging with In-111 ibritumomab tiuxetan

Severe cutaneous and mucocutaneous reactions, some with fatal outcome, may occur in association with the ibritumomab tiuxetan therapeutic regimen

Do not administer to patients experiencing a severe cutaneous or mucocutaneous reaction and provide prompt medical evaluation

Points of recommendation

Have blood work checked as you have been told by the doctor. Talk with the doctor.

  You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.

  You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.

  Talk with your doctor before getting any vaccines while you take ibritumomab tiuxetan and after you stop taking it. Vaccine use with ibritumomab tiuxetan may either raise the chance of an infection or make the vaccine not work as well. Talk with your doctor.

  If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.

  A bone marrow problem called myelodysplastic syndrome (MDS) and a type of leukemia have rarely happened in patients treated with ibritumomab tiuxetan. Sometimes, this has been deadly. Talk with your doctor.

  This medicine may cause harm to the unborn baby if you take it while you are pregnant.

  Use birth control that you can trust during care and for 12 months after care ends.

  If you get pregnant while taking ibritumomab tiuxetan or within 12 months after your last dose, call your doctor right away.

Pregnancy level

D

Related drugs

Tositumomab , Rituximab


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