tositumomab (Discontinued)

Brand and Other Names:Bexxar
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injectable solution

  • 14mg/mL
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Non-Hodgkin's Lymphoma

August 7, 2013: GlaxoSmithKline announced that tositumomab manufacture and sales will be discontinued

Indicated for the treatment of CD20 antigenexpressing relapsed or refractory, low grade, follcular, or transformed non-Hodgkin's lymphoma, including patients with rituximab-refractory non-Hodgkin s lymphoma

Dosimetric step

  • Tositumomab 450 mg IV in 50 mL NS over 60 minutes
  • I-131 tositumomab IV in 30 mL NS over 20 minutes

Therapeutic step 7-14 days later

  • Do not administer this step if biodistribution is altered
  • Tositumomab 450 mg IV in 50 ml NS over 60 minutes
  • I-131 tositumomab dose depends on platelet count
  • - >150 K/cu.mm: dose to deliver 75 cGy total body irradiation and 35 mg tositumomab, IV over 20 minutes
  • - >100-150 K/cu.mm: dose to deliver 65 cGy total body irradiation and 35 mg tositumomab, IV over 20 minutes

At any step, decrease rate by 50% for mild to moderate infusional toxicity

Interrupt infusion for severe toxicity; resume after complete resolution with 50% dose reduction

Management of Ifusion Related Toxicity

Mild-to-moderate: Reduce infusion rate by 50%

Severe tosicity: Stop infusion; resume at 50% infusion rate after complete resolution of toxicity

Concomitant Medications

Thryoid protective agents: SSKI 4 gtt PO q8hr; Lugol's solution 20 gtt PO q8hr; or potassium iodide tabs 130 mg PO qDay; must be initiated 24 hours before dosimetric step and continued 14 days after therapeutic step

Acetaminophen 650 mg PO 30 minutes prior to admin of tositumomab

Diphenhydramine 50 mg PO 30 minutes prior to admin of tositumomab

Monitor

CBC with diff and Plts prior to and weekly following Bexxar (minutes 10 weeks)

TSH at treatment and annually

SCr immediately prior to therapeutic regimen

Other Indications & Uses

Single course of treatment; safety of multiple courses or combo with other forms of treatment has not been evaluated

CD20 positive, follicular NHL with and without transformation, refractory to rituximab and relapsed following chemotherapy

Not recommended

Indicated for the treatment of CD20 antigenexpressing relapsed or refractory, low grade, follcular, or transformed non-Hodgkin's lymphoma, including patients with rituximab-refractory non-Hodgkin s lymphoma

Non-Hodgkin's Lymphoma

Dosimetric step

Tositumomab 450 mg IV in 50 mL NS over 60 minutes

I-131 tositumomab IV in 30 mL NS over 20 minutes

Therapeutic step 7-14 days later

Do not administer this step if biodistribution is altered

Tositumomab 450 mg IV in 50 ml NS over 60 minutes

I-131 tositumomab dose depends on platelet count

- >150 K/cu.mm: dose to deliver 75 cGy total body irradiation and 35 mg tositumomab, IV over 20 minutes

- >100-150 K/cu.mm: dose to deliver 65 cGy total body irradiation and 35 mg tositumomab, IV over 20 minutes

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Adverse Effects

>10%

Cytopenia, Grade 3-4 (71%)

Asthenia (46-50%)

Fever (36-40%

Nausea (36-40%)

Infection (21-25%)

Pain (16-20%)

Chills (16-20%)

Headache (16-20%)

Abd. pain (11-15%)

Vomiting (11-15%)

Anorexia (11-15%)

Diarrhea (11-15%)

Myalgia (11-15%)

<10%

Methemoglobinemia (rare)

Syncope

Prolonged bleeding time

Exfoliative dermatitis

Unstable angina

Rebound hypertension

Thrombocytopenia

Hypotension

Peripheral edema

Dizziness

Somnolence

Dyspepsia

Weight loss

Hypothroidism

Back pain

Chest pain

Neck pain

Arthralgia

Myelodysplastic syndrome &/or acute leukemia

Frequency Not Defined

Hypersensitivity, including anaphylaxis- frequency unspecified; pts positive for HAMA (human anti-mouse antibodies) may be at incr risk of anaphylaxis

Hyperthyroidism

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Warnings

Black Box Warnings

Hypersensitivity reactions, including anaphylaxis

  • Serious and sometimes fatal hypersensitivity reactions reported. Medications for the treatment of such reactions should be available for immediate use. Discontinue therapeutic regimen and provide medical attention to patients who develop severe hypersensitivity reactions

Prolonged and severe cytopenias

  • Severe thrombocytopenia and neutropenia have been reported in most patients. Do not administer therapy to patients with >25% lymphoma marrow involvement and/or impaired bone marrow reserve

Special requirements

  • The drug should be administered under the supervision of a physician with experience and training in the handling of therapeutic radionuclides and administered by care providers that have been certified or are in the process of being certified by the manufacturer in dose calculation and administration of the therapeutic regimen

Contraindications

Hypersensitivity to any component or to another monoclonal antibody

Not indicated for initial treatment

Cautions

Anaphylaxis may occur; discontinue regimen if severe hypersensitivity occurs

Risk of prolonged and severe cytopenia; do not treat patient with >25% lymphoma marrow involvement or impaired bone marrow reserve

Patients will be radioactive for several days

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Pregnancy & Lactation

Pregnancy Category: X (can cause fatal harm when administered during pregnancy)

Lactation: Incompatible with breastfeeding

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Monoclonal antibody to CD20 antigen;  may cause induction of apoptosis, complement dependent cytotoxicity, and Ab-dependent cytotoxicity

Pharmacokinetics

Blood Clearance: 68.2 mg/hr

Half-life elimination: 67hr (28-115hr range)

Patients with high tumor burden, splenomegaly or bone marrow involvement have faster clearance, shorter half life and larger Vd

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Administration

IV Incompatibilities

Do not mix or dilute with other drugs

IV Preparation

Dilute prior to IV infusion

IV Administration

Infuse tositumomab over 60 min

Infuse iodine I 131 tositumomab over 20 min

Administer via a IV tubing set with an inline 0.22 micron filter

Use same IV tubing set and filter throughout entire dosimetric or therapeutic step; changing filters can cause up to a 7% loss in iodine I 131 tositumomab dose

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Images

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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.