Dosing and uses of Bexxar (tositumomab)
Adult dosage forms and strengths
injectable solution
- 14mg/mL
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
Pediatric dosage forms and strengths
Not recommended
Geriatric dosage forms and strengths
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
Bexxar (tositumomab) adverse (side) 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
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
Pregnancy and 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.
Pharmacology of Bexxar (tositumomab)
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
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
