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En Espanol 
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Pronunciation(toe si TYOO mo mab & EYE oh dyne eye one THUR tee one toe si TYOO mo mab)
U.S. Brand NamesBexxar®
SynonymsAnti-CD20-Murine Monoclonal Antibody I-131; B1; B1 Antibody; 131 I Anti-B1 Antibody; 131 I-Anti-B1 Monoclonal Antibody; Iodine I 131 Tositumomab and Tositumomab; Tositumomab I-131
Generic AvailableNo
UseTreatment of relapsed or refractory CD20 positive, low-grade, follicular, or transformed non-Hodgkin's lymphoma
Pregnancy Risk FactorX
Pregnancy ImplicationsIodine-131 crosses the placenta and may cause severe and irreversible hypothyroidism in neonates. Pregnancy should be ruled out prior to therapy. Males and females should be instructed to use effective contraception for 12 months following treatment.
LactationEnters breast milk/contraindicated
ContraindicationsHypersensitivity to murine proteins or any component of the formulation; pregnancy; breast-feeding
Warnings/PrecautionsHypersensitivity reactions (including anaphylaxis) have been reported. Patients should be screened for human antimouse antibodies (HAMA); may be at increased risk of allergic or serious hypersensitivity reactions. Hematologic toxicity was reported to be the most common adverse effect with 27% patients requiring supportive care. Severe or life-threatening cytopenias (NCI CTC grade 3 or 4) have been reported in a large number of patients; may be prolonged and severe. Secondary malignancies have been reported following use.Treatment involves radioactive isotopes; appropriate precautions in handling and administration must be followed. Patients must be instructed in measures to minimize exposure of others. Women of childbearing potential should be advised of potential fetal risk; effective contraceptive measures should be used for 12 months following treatment (males and females). Treatment may lead to hypothyroidism; patients should receive thyroid-blocking medications prior to the start of therapy. Patients should be premedicated to prevent infusion related reactions. For a single course of therapy only; multiple courses or use in combination with other chemotherapy or irradiation have not been studied. Safety has not been established in patients with >25% lymphoma marrow involvement, platelet count <100,000 cells/mm3 or neutrophil count <1500 cells/mm3. Use caution with cardiovascular disease, renal, or hepatic impairment. Safety and efficacy have not been established with impaired renal function or in pediatric patients.
Adverse Reactions>10%: Central nervous system: Fever (37%), pain (19%), chills (18%), headache (16%) Dermatologic: Rash (17%) Endocrine & metabolic: Hypothyroidism (7% to 19%) Gastrointestinal: Nausea (36%), abdominal pain (15%), vomiting (15%), anorexia (14%), diarrhea (12%) Hematologic: Neutropenia (grade 3 or 4, 63%); thrombocytopenia (grade 3 or 4, 53%) Time to nadir: 4-7 weeks Duration: 30 days (>90 days in 5% to 7% of patients) Neuromuscular & skeletal: Weakness (46%), myalgia (13%) Respiratory: Cough (21%), pharyngitis (12%), dyspnea (11%) Miscellaneous: Infusion-related reactions (26%, occurred within 14 days of infusion, included bronchospasm, chills, dyspnea, fever, hypotension, nausea, rigors, diaphoresis), infection (21%), HAMA-positive seroconversion (11%; up to 21% at 1 year) 1% to 10%: Cardiovascular: Hypotension (7% to 10%), peripheral edema (9%), chest pain (7%), vasodilation (5%) Central nervous system: Dizziness (5%), somnolence (5%) Dermatologic: Pruritus (10%) Gastrointestinal: Constipation (6%), dyspepsia (6%), weight loss (6%) Local: Injection site hypersensitivity Neuromuscular & skeletal: Arthralgia (10%), back pain (8%), neck pain (6%) Respiratory: Rhinitis (10%), pneumonia (6%), laryngismus Miscellaneous: Diaphoresis (8%), hypersensitivity reaction (6%), secondary leukemia/myelodysplastic syndrome (3%; up to 6% at 5 years), anaphylactoid reaction, secondary malignancies, serum sickness
Overdosage/ToxicologyGrade 4 hematologic toxicity lasting 18 days was reported in one patient accidentally receiving a total body dose of 88 cGy. Monitor for cytopenias and radiation-related toxicity.
Drug InteractionsNo formal drug interaction studies have been conducted.Vaccines: The ability of patients receiving tositumomab to generate humoral response (primary or anamnestic) to vaccination is unknown. Safety of live vaccines has not been established.
StabilityTositumomab: Store under refrigeration at 2°C to 8°C (36°F to 46°F); protect from strong light; do not freeze. Withdraw and discard 32 mL of saline from a 50 mL bag of NS. Add contents of both 225 mg vials of tositumomab (total 32 mL) to remaining NS to make a final volume of 50 mL. Gently mix by inverting bag, do not shake. Following dilution, tositumomab is stable for 24 hour when refrigerated or 8 hours at room temperature. Iodine I 131 tositumomab: Store frozen at less than or equal to -20°C in the original lead pots. Allow 60 minutes for thawing at ambient temperature. Calculate volume required for an iodine I 131 tositumomab activity of 5 mCi (specification sheet provided with product). If the amount of tositumomab contained in the iodine I 131 tositumomab solution contains <35 mg of tositumomab, use the 35 mg vial of tositumomab to prepare a final concentration of tositumomab 35 mg. Using NS, the final volume should equal 30 mL. Solutions for infusion are stable for up to 8 hours at 2°C to 8°C (36°F to 46°F) or room temperature.
Mechanism of ActionTositumomab is a murine IgG2a lambda monoclonal antibody which binds to the CD20 antigen, expressed on B-lymphocytes and on >90% of B-cell non-Hodgkin's lymphomas. Iodine I 131 tositumomab is a radio-iodinated derivative of tositumomab covalently linked to iodine 131. The possible actions of the regimen include apoptosis, complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and cell death. Administration results in depletion of CD20 positive cells.
Pharmacodynamics/KineticsDistribution: Tositumomab: Vd increased with high tumor burden, splenomegaly, or bone marrow involvement Half-life elimination: Tositumomab: Elimination: 36-48 hours Terminal half-life decreased with high tumor burden, splenomegaly, or bone marrow involvement Clearance: Blood: 68.2 mg/hour Excretion: Iodine-131: Urine (98%) and decay
DosageI.V.: Adults: Dosing consists of four components administered in 2 steps. Thyroid protective agents (SSKI, Lugol's solution or potassium iodide), acetaminophen and diphenhydramine should be given prior to or with treatment. Refer to Additional Information.Step 1: Dosimetric step (Day 0): Tositumomab 450 mg in NS 50 mL administered over 60 minutes Iodine I 131 tositumomab (containing I-131 5.0 mCi and tositumomab 35mg) in NS 30 mL administered over 20 minutes Note: Whole body dosimetry and biodistribution should be determined on Day 0; days 2, 3, or 4; and day 6 or 7 prior to administration of Step 2. If biodistribution is not acceptable, do not administer the therapeutic step. On day 6 or 7, calculate the patient specific activity of iodine I 131 tositumomab to deliver 75 cGy TBD or 65 cGy TBD (in mCi). Step 2: Therapeutic step (Day 7): Tositumomab 450 mg in NS 50 mL administered over 60 minutes Iodine I 131 tositumomab: Platelets Platelets
AdministrationI.V.: Reduce the rate of infusion by 50% for mild-to-moderate infusion-related toxicities; interrupt for severe toxicity. Once severe toxicity has resolved, infusion may be restarted at half the previous rate. The same IV tubing set with an in-line 0.22 micron filter should be used for the entire dosimetric or therapeutic step. Changing filters may result in loss of drug. Prior to infusion, patients should be premedicated and a thyroid-protective agent should be started.
Monitoring ParametersCBC with differential (prior to therapy and at least weekly for a minimum of 10 weeks); TSH (prior to therapy and yearly); serum creatinine (immediately prior to administration)Following infusion of the iodine I 131 tositumomab dosimetric dose, the total body gamma camera counts and whole body images should be taken within 1 hour of the infusion and prior to urination, and 2-4 days after the infusion and following urination, and 6-7 days after the infusion and following urination.
Test InteractionsMay interfere with tests using murine antibody technology.
Patient EducationInform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medications during therapy without consulting prescriber. This medication can only be administered by intravenous infusion. You will be closely monitored prior to, during, and following infusion. Report immediately any immediate chills, nausea, diaphoresis; difficulty swallowing or breathing; tightness in chest or chest pain. You will have frequent laboratory tests following therapy to assess effectiveness and response. Other medication will be prescribed related to this therapy. Take as directed; do not stop or alter dosage without consulting prescriber. You may experience nausea, vomiting, abdominal pain (if persistent, contact prescriber for medication); loss of appetite (small, frequent meals and frequent mouth care may help). Report immediately any chills, persistent or acute headache, fever, rash, swelling of extremities, chest pain, muscle or back pain, upper respiratory symptoms (sore throat, runny nose, persistent cough, pneumonia), signs of infection, or other adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant (females) or cause a pregnancy (males) during therapy or for 12 months following therapy. Consult prescriber for appropriate contraceptives. This medication will cause severe fetal defects. Do not give blood during therapy of for 12 months following therapy. Do not breast-feed.
Additional InformationThyroid protective agent: One of the following agents should be used starting at least 24 hours prior to the dosimetric dose and continued for 2 weeks after the therapeutic dose. Therapy should not begin without using one of the following agents:SSKI: 4 drops 3 times/day Lugol's solution: 20 drops 3 times/day Potassium iodide: 130 mg once daily
Dental Health: Effects on Dental TreatmentNo significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Mental Health: Effects on Mental StatusMay cause sedation
Mental Health: Effects on Psychiatric TreatmentHematologic adverse reactions are common; use caution with clozapine, carbamazepine, valproic acid and derivatives, and mirtazapine. Rash is common; consider in differential in patients receiving lamotrigine. GI side effects are common; concurrent use with SSRIs may produce additive effects. May produce hypotension; concurrent use with psychotropic agents may produce additive blood pressure-lowering effects.
Dosage FormsNote: Not all components are shipped from the same facility. When ordering, ensure that all will arrive on the same day.Kit [dosimetric package] (Bexxar®): Tositumomab 225 mg/16.1 mL [2 vials], tositumomab 35 mg/2.5 mL [1 vial], and iodine I 131 tositumomab 0.1 mg/mL and 0.61mCi/mL (20 mL) [1 vial] Kit [therapeutic package] (Bexxar®): Tositumomab 225 mg/16.1 mL [2 vials], tositumomab 35 mg/2.5 mL [1 vial], and iodine I 131 tositumomab 1.1 mg/mL and 5.6 mCi/mL (20 mL) [1 or 2 vials]
ReferencesKaminski MS, Zelenetz AD, Press OW, et al, "Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade B-Cell Non-Hodgkin's Lymphomas,"J Clin Oncol, 2001, 19(19):3918-28. Press OW, Eary JF, Appelbaum FR, et al, "Phase II Trial of 131I-B1 (Anti-CD20) Antibody Therapy With Autologous Stem Cell Transplantation for Relapsed B Cell Lymphomas,"Lancet, 1995, 346(8971):336-40. Press OW, Eary JF, Appelbaum FR, et al, "Radiolabeled-Antibody Therapy of B-Cell Lymphoma With Autologous Bone Marrow Support,"N Engl J Med, 1993, 329(17):1219-24.
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150,000/mm3: Iodine I 131 calculated to deliver 75 cGy total body irradiation and tositumomab 35 mg over 20 minutes
