Adult Dosing

Non-Hodgkin's lymphoma

• Dosimetric dose followed by 7 to 14 days later by the therapeutic step
• Dosimetric dose:
• IV: Tositumomab 450 mg in 50 mL 0.9% NaCl over 60 mins
• IV: Iodine I 131 tositumomab (5.0mCi iodine-131 and 35 mg tositumomab) in 30 mL 0.9% NaCl over 20 mins
• Reduce rate of infusion by 50% for mild/moderate infusional toxicity; interrupt therapy for severe toxicity, resume with 50% reduction in rate of infusion after complete resolution of severe toxicity
• Whole body dosimetry and biodistribution must be obtained within 1 hour of the end of the infusion of the iodine I-131 tositumomab dosimetric dose before the patient voids
• DAY 2 to 4: Perform whole body dosimetry and biodistribution after the iodine I-131 tositumomab dosimetric dose and immediately after the patient voids. Repeat process 6 to 7 days after the administration of the I-131 tositumomab dosimetric dose to resolve any ambiguities. If the biodistribution is altered the therapeutic dose should not be administered

• Therapeutic dose:
• IV: Tositumomab 450 mg in 50 mL 0.9% NaCl over 60 mins
• Reduce rate of infusion by 50% for mild/moderate infusional toxicity; interrupt therapy for severe toxicity, resume with 50% reduction in rate of infusion after complete resolution of severe toxicity
• IV: Iodine I 131 tositumomab (as follows)
• 150000 platelets/mm³: Recommended dose is the activity of Iodine-131 calculated to deliver 75 cGy total body irradiation and 35 mg tositumomab IV over 20 mins

• Safety and efficacy is established only for setting of patients receiving thyroid blocking agents and prior medication to ameliorate/prevent infusion reactions
• Therapeutic dose should be given 7-14 days after dosimetric dose
• Initiate thyroid protective agents at least 24 hrs prior to administering Iodine I 131 of dosimetric dose step and continued until 2 wks after administration of iodine I 131 tositumomab therapeutic dose
• Patients must receive saturated solution of potassium iodide (SSKI) 4 drops PO tid, lugol's solution 20 drops PO tid; or potassium iodide 130 mg PO daily before starting therapy; do not start dosimetric step of Iodine I 131 tositumomab if not received at least 3 doses of SSKI, 3 doses of lugol's soln or 1 dose of 130 mg potassium iodide (at least 24 hrs prior to dosimetric dose)
• Administer acetaminophen 650 mg PO and diphenhydramine 50 mg PO 30 minutes prior to administration of tositumomab in the dosimetric and therapeutic steps
• See the dosimetry methodology and administration set-up supplied with the packaging for more specific details

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• CD20 antigen-expressing relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma with progression during and after Rituximab therapy, including patients with Rituximab-refractory non-Hodgkin’s lymphoma

• Hypersensitivity to any of the ingredients of the product
• Iodine preparation hypersensitivity
• Initial treatment of patients with CD20 positive non-Hodgkin’s lymphoma
• Lactation
• Multiple courses
• Concurrent use with other forms of irradiation or chemotherapy
• Renal impairment
• Intolerance to thyroid blocking agents

• Only physicians qualified and experienced in safe use and handling of therapeutic radionuclides should administer the drug. Physicians should be certified or should be in the process of being certified by GlaxoSmithKline for dose calculation and administration of the tositumomab therapeutic regimen
• Serious anaphylactic hypersensitivity reactions, sometimes fatal, have been reported with the therapeutic regimen. Emergency use medicines such as epinephrine, antihistamines, corticosteroids should be available for immediate use. Discontinue therapy if serious reactions occur, provide medical care
• Prolonged and severe thrombocytopenia & neutropenia has occurred in majority of patients who received the therapeutic regimen. Do not administer to patients with >25% lymphoma marrow involvement and/or impaired bone marrow reserve, platelet count < 100,000 cells/mm³ or neutrophil count < 1500 cells/mm³
• Has been assigned pregnancy category X. It can cause fetal harm when administered to a pregnant woman

Thrombocytopenia

• NCI Grade I thrombocytopenia: Recommended therapeutic dose is the activity of Iodine-131 calculated to deliver 65 cGy total body irradiation and 35 mg tositumomab IV over 20 mins

Renal Dose Adjustment

• Renal impairment: Avoid use

Hepatic Dose Adjustment

• Hepatic impairment: Dose adjustments not defined

See Supplemental Patient Information

• Severe or fatal cytopenias of NCI CTC grade 3 or 4 have occurred, time to nadir is approx 4 to 7 wks and duration of cytopenias is approximately 30 days, thrombocytopenia, neutropenia, and anemia can persist for more than 90 days following administration
• Safety and efficacy have not been established in patients with >25% lymphoma marrow involvement and/or impaired bone marrow reserve, platelet count < 100,000 cells/mm³ or neutrophil count < 1500 cells/mm³
• Infections, hemorrhage have occurred following severe cytopenias , a requirement for growth factors (12% G- or GM-CSF, 7% Epoetin alfa) and blood product support is needed
• Serious anaphylactic hypersensitivity reactions, sometimes fatal, have been reported with the therapeutic regimen. Emergency use medicines such as epinephrine, antihistamines, corticosteroids should be available for immediate use. Discontinue therapy if serious reactions occur, provide medical support (US Black box warning)
• Screen patients received murine proteins for human antimouse antibodies (HAMA), patients detected for HAMA are more prone to anaphylaxis and serious hypersensitivity reactions
• Impaired renal function may decrease rate of excretion of radiolabeled iodine, increasing exposure to the radioactive component
• Myelodysplastic syndrome (MDS), acute leukemia, non-hematological malignancies have occurred in patients
• Take utmost care to follow radiation safety practices and applicable federal guidelines
• Safety and efficacy is not established in patients with impaired renal function
• Safety and efficacy is not established for immunization with live viral vaccines following administration therapeutic regimen, ability to generate a primary or anamnestic humoral response to any vaccine in patients received tositumomab is not studied
• During discharge provide patients with both oral and written instructions for minimizing exposure of family members, friends and the general public to radioactive material present in body for approximately one week after dosage
• Monitor complete blood counts weekly for 10-12 weeks or until persistence of cytopenia, nonitor for evidence of moderate or more severe cytopenias; Monitor thyroid stimulating hormone (TSH) level before initiation of treatment and annually thereafter, monitor serum creatinine levels prior to administration of drug

Cautions: Use cautiously in

• Presence of human anti-mouse antibodies (HAMA)
• Geriatrics
• Pediatrics

Supplemental Patient Information

• Inform patients about the presence of radioactive material in their body for several days upon their release from the hospital or clinic following administration of drug

Pregnancy Category:X

Breastfeeding: Unsafe. contraindicated for use in pregnant women, nursing women should be advised to discontinue breastfeeding

• CNS: Somnolence, asthenia, dizziness, drowsiness, headache, weakness
• CV: edema, hypotension. chest pain, vasodilatation
• GI: Dyspepsia, abdominal pain, diarrhea, nausea, vomiting. anorexia, diarrhea, constipation
• IMMUN: Antibody development, Human anti-murine
• ENDO: Hypothyroidism
• HEMA: Neutropenia, thrombocytopenia, anemia
• RESP: Increased cough, pharyngitis, dyspnea, pneumonia, rhinitis
• METABOLIC: Weight loss
• MUSC: Back pain, neck pain, myalgia, arthralgia
• LOCAL: Peripheral edema
• DERM: Pruritus, sweating, rash
• HYPERSENSITIVITY: Allergic reaction, face edema, injection site hypersensitivity, anaphylactic reaction, laryngismus, serum sickness
• MISC: Infusional toxicity, fever, pain, secondary malignancies, infection, pain, chills, pleural effusion, pneumonia, cancer (MDS), leukemia

• Monoclonal antibody; induces apoptosis, blocks complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity present on surface of normal and malignant B lymphocytes resultingh in cell death associated with ionizing radiation from the radioisotope
• Likely to be cleared by opsonization via the reticuloendothelial system when bound to B lymphocytes, or by human antimurine antibody production
• Excreted in urine
• Half-life: 67 hours (range 28-115 hours)

US Trade Name(s)

• Bexxar

US Availability

Bexxar (supplied as a kit)

• Dosimetric step kit:
• INJ: Tositumomab (Two single use 225 mg vials (16.1mL) + one single use 35 mg vial (2.5mL)
• INJ: Iodine I 131 Tositimomab (One single use not < 20mL

• Therapeutic step kit:
• INJ: Tositumomab (Two single use 225 mg vials (16.1mL) + one single use 35 mg vial (2.5mL)
• INJ: Iodine I 131 Tositimomab (One or two single use not < 20mL)

Canadian Trade Name(s)

• Bexxar

Canadian Availability

Bexxar (supplied as a kit)

• INJ: Tositumomab (Two single use 225 mg vials (16.1mL) + one single use 35 mg vial (2.5mL)
• INJ: Iodine I 131 Tositimomab (20 mL vial for dosimetric dose)
• INJ: Iodine I 131 Tositimomab (20 mL vial for therapeutic dose)

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Hematology/Oncology

Antineoplastics

Monoclonal Antibodies