tositumomab


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tositumomab (I 131 tositumomab)

(to-si-too-mo-mab) ,

Bexxar

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: monoclonal antibodies
Pregnancy Category: X

Indications

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

Action

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

Therapeutic effects

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)

ROUTEONSETPEAKDURATION
IVunknown7 wk12 wk

Contraindications/Precautions

Contraindicated in: Hypersensitivity to murine (mouse) proteins; Obstetric / Lactation: 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; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness
  • drowsiness
  • headache
  • weakness

Cardiovascular

  • edema
  • hypotension

Gastrointestinal

  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)

Endocrinologic

  • hypothyroidism

Hematologic

  • neutropenia
  • thrombocytopenia
  • anemia (most frequent)

Metabolic

  • weight loss

Musculoskeletal

  • arthralgia
  • back pain
  • myalgia
  • neck pain

Miscellaneous

  • hypersensitivity reactions including anaphylaxis (life-threatening)
  • infusional toxicity (most frequent)
  • fever
  • pain
  • secondary malignancies

Interactions

Drug-Drug interaction

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.
Intravenous (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

Nursing implications

Nursing assessment

  • Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify 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 ≥25%, 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 Reactions)

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%.
  • Intravenous Administration
  • Intermittent Infusion: Diluent: Dilute tositumomab 450 mg in 50 mL of 0.9% NaCl. Concentration: Concentration will be 9 mg/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.

Bexxar

A monoclonal antibody plus radiolabeled 131I-monoclonal antibody, used to manage patients with CD20 positive follicular NHL, whose disease is refractory to rituximab and has relapsed post-chemotherapy.
 
Adverse effects
Prolonged/severe neutropenia, thromobocytopenia, anaemia, pneumonia, pleural effusion, dehydration.
References in periodicals archive ?
The maximum range in the healthy tissue for tositumomab is only 2.
Another novel yet effective treatment is radio immunotherapy (RIT) which allows delivery of radiation to lymphoma cells using radioimmunoconjugates ([131]I- tositumomab and [90]Y-ibritutomomab tiuxetan have been approved till now) that target the CD20 antigen and are being used in the setting of recurrent follicular lymphoma setting.
The antineoplastic agents are alemtuzumab (Campath), bevacizumab (Avastin), cetuximab (Erbitux), gemtuzumab ozogamicin (Mylotarg), ibritumomab tiuxetan (Zevalin), panitumumab (Vectibix), tositumomab and iodine 131 (Bexxar), and trastuzumab (Herceptin).
Marketed antibody drugs and advanced candidates are often directed to the same target and there are apparently four TNF[alpha] antagonists (infliximab, adalimumab, golimumab, certolizumab) in addition to the Fc fusion protein etanercept, five antibodies targeting the B cell receptor CD20 (rituximab, ibritumomab, tositumomab, ofatumumab, ocrelizumab), five to the EGF receptor EGFR (cetuximab, panitumumab, matuzumab, nimotuzumab, zalatumumab), and three to VEGF / VEGFR signalling (bevacizumab, ranibizumab, CDP-791) in addition to the Fc fusion VEGF-Trap.
Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: Five-year follow-up of Southwest Oncology Group Protocol S9911.
In one study, the combined use of radioimmunotherapy with the anti-CD20 monoclonal antibody tositumomab and autologous hematopoietic stem cell transplantation was shown to be beneficial in adults aged 60 and over with high-risk relapsed or refractory B-cell lymphoma, Dr.
Radioimmunotherapy consisting of radiolabeled antibodies (such as tositumomab and ibritumomab) targeted to CD20 antigens on cancer cells in patients with relapsed or refractory FL has yielded overall response rates of about 80%, said Dr.
Overview: Abciximab, Arcitumomab, Basiliximab, Capromab, Cotara, Daclizumab, Edrecolomab, Igovomab, Nofetumomab, Satumomab, Sulesomab, Tositumomab and Votumumab
G3001, Administration and supply of tositumomab, 450mg, for the infusion of non-radioactive tositumomab during the dosimetric step and the infusion of non-radioactive tositumomab during the therapeutic step.
Under a separate agreement, Boehringer Ingelheim Pharma KG produces bulk tositumomab, which is sent to MDS Nordion for radiolabeling.
Iodine 131 has a well-established safety profile in the treatment of thyroid disease and tositumomab has anti-tumor activity of its own.