General

Pronunciation
to-si-TOO-mo-mab


Trade Name(s)

• Bexxar

Pregnancy Category
Category X

Ther. class.
antineoplastics

Pharm. class.
monoclonal antibodies
radiolabled monoclonal antibodies

Indications

CD20 positive, follicular, non-Hodgkin's lymphoma refractory to rituximab and in relapse

Action

Binds to CD20 antigens on the surface of specific lymphocytes producing antibody-mediated cytotoxicity and cell death due to ionizing radiation

Therapeutic Effect(s):
Sustained depletion of CD20 lymphocytes, with decreased progression of lymphoma

Pharmacokinetics

Absorption: IV administration results in complete bioavailability

Distribution: Unknown

Metabolism and Excretion: Excreted primarily by kidneys

Half-life: Unknown

TIME/ACTION PROFILE (depletion of lymphocytes)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	7 wk	12 wk

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to murine (mouse) proteins

• Pregnancy or lactation

• Intolerance to thyroid blocking agents (these agents are required concurrently)

Use Cautiously in:

• >25% lymphoma marrow involvement, platelet count <100,000 cells/mm³, neutrophil count <15,000 cells/mm³ (safety not established)

• Presence of human anti-mouse antibodies (HAMA; ↑ risk of serious hypersensitivity including anaphylaxis)

• Impaired renal function

• Children (safety not established)

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, headache, weakness.

CV: edema, hypotension.

GI: abdominal pain, diarrhea, nausea, vomiting.

Endo: hypothyroidism.

Hemat: NEUTROPENIA, THROMBOCYTOPENIA, anemia.

Metabolic: weight loss.

MS: arthralgia, back pain, myalgia, neck pain.

Misc: hypersensitivity reactions including anaphylaxis, infusional toxicity, fever, pain, secondary malignancies.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.
*CAPITALS/italic indicates life-threatening and most frequent.

Interactions

Drug-Drug

• May ↓ response to and ↑ risk of adverse reactions to live-virus vaccines

• Anticoagulants or agents interfering with platelet function may ↑ risk of bleeding

Route/Dosage

• Pretreatment with thyroid blocking agents and premedication to prevent infusional reactions is required

• IV (Adults): Dosimetric step—tositumomab 450 mg and Iodine I 131 tositumomab (containing 5 mCi I-131 and 35 mg tositumomab), followed 7–14 days later by therapeutic step. Therapeutic step—tositumomab 450 mg and Iodine I 131 tositumomab (dose calculated by formulae and information provided with packaging); administer only if biodistribution is not altered.

Availability

These products are shipped only to practitioners who are participating in certification or are certified in preparation and administration of Bexxar. Dosimetric packaging is shipped from separate sites and must arrive simultaneously

• Tositumomab for injection: package contains 2–225 mg vials and one 35 mg vial; concentration 14 mg/mL

• I 131 Tositumomab for injection: 1 or 2 single-use vials containing not <20 mL of Iodine I 131 tositumomab at nominal protein and activity concentrations of 1.1 mg/mL and 5.6 mCi/mL at calibration. Refer to product specification sheet for more specific information

Assessment

• Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify physician or other health care professional immediately if these symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction

• Monitor for infusional toxicity (fever, rigors, chills, sweating, hypotension, dyspnea, bronchospasm, nausea) during or within 48 hr of infusion; may also occur within 14 days of dosimetric dose. May pretreat with acetaminophen 650 mg and diphenhydramine 50 mg PO 30 min prior to dosimetric and therapeutic steps. If infusional toxicity occurs, slow and/or temporarily interrupt infusion

• Monitor for signs of hypothyroidism (bradycardia, weight gain, lethargy) periodically during therapy

Lab Test Considerations

• Monitor CBC prior to and at least weekly for at least 10–12 wks or until severe cytopenias have resolved. May cause thrombocytopenia, neutropenia, and anemia lasting 30–90 days with a nadir in 4–7 wks. If lymphoma marrow involvement is B25%, platelet count is <100,000cells/mm³ or neutrophil count is <1,500 cells/mm³, re-evaluate use of tositumomab

» May cause hypothyroidism. Monitor serum TSH levels before treatment and annually thereafter

» Monitor serum creatinine levels immediately prior to administration

Potential Nursing Diagnoses

• Risk for injury (Adverse Reaction)

Implementation

Tositumomab should be used only by health care professionals qualified by training in the safe use of therapeutic radionuclides

» All patients must receive thyroid blocking agents; patients unable to tolerate thyroid blocking agents should not receive tositumomab

» Reduce infusion rate by 50% for mild to moderate infusional toxicity; interrupt infusion for severe infusional toxicity. When symptoms have resolved, resume rate at 50%

IV Adminstration:

• Intermittent Infusion:

Diluent: Dilute tositumomab 450 mg in 50 mL of 0.9% NaCl.
Concentration: Concentration will be 9mg/mL Solution should be clear to opalescent and colorless to slightly yellow. Administer via IV tubing set with a 0.22 micron filter. Same IV tubing set and filter must be used throughout entire dosimetric or therapeutic step. Change in filter can result in loss of drug

• Rate:
Administer over 60 min
Dilute iodine I 131 tositumomab in 30 mL of 0.9% NaCl

• Rate:
Administer over 20 min

Patient/Family Teaching

• Inform patient that they will have a radioactive material in their body for several days upon discharge from hospital. Provide patient with verbal and written instructions for minimizing exposure to family, friends, and general public

• Advise patient to use effective contraception for 12 mo following administration. Advise patient not to breastfeed during this time

• Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding. Explain the need for frequent monitoring

• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known

• Emphasize the importance of adherence with thyroid blocking agents and need for long-term monitoring

Evaluation/Desired Outcomes

Sustained depletion of CD20 lymphocytes, with decreased progression of lymphoma

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