Drug information of Tositumomab
Murine IgG2a lambda monoclonal antibody against CD20 antigen (2 heavy chains of 451 residues, 2 lambda chains of 220 residues). It is produced in an antibiotic-free culture of mammalian cells. It can be covalently linked to Iodine 131 (a radioactive isotope of iodine).
Mechanism of effect
Binds to the CD20 antigen which is found on mature B lymphocytes. The antibody binding appears to induce apoptosis, complement-dependent cytotoxicity and cell death through ionizing radiation.
Tositumomab binds to the CD20 antigen, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin's lympohomas. The antibody leads to selective killing of B-cells.
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
Route of elimination: Elimination of Iodine-131 occurs by decay and excretion in the urine.
- 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
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
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
- 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
Points of recommendation
After you are treated with Tositumomab, your body will retain radioactive material for several days. During this time you will be giving off a small amount of radiation to others around you. Your caregivers should give you instructions about how to avoid exposing other people to radiation until this effect wears off.
Tositumomab can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood will need to be tested every 3 months during treatment and possibly for a short time after you stop receiving this medicine.
While you are being treated with Tositumomab, wash your hands often to prevent infections.
Tositumomab can increase your risk of developing hypothyroidism (underactive thyroid). You will be given other medications to protect your thyroid gland and to help prevent allergic reactions. You may need to keep taking some of these medications after your treatment ends.
Take all medications your doctor prescribes to help protect your thyroid gland. You may need to have blood tests to check your thyroid function at regular intervals for the rest of your life. Visit your doctor regularly.
Tositumomab can cause unusual results with certain medical tests. You may also have an allergic reaction to diagnostic tests or treatments using mouse proteins or monoclonal antibodies. Tell any doctor who treats you that you have been treated with Tositumomab.
Tositumomab can pass into body fluids (including urine, feces, or vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Avoid handling any of your body fluids without wearing latex rubber gloves. If another person is handling your fluids, they should wear gloves, eye protection, and a mask to cover the nose and mouth.
Body fluids should not be handled by a woman who is pregnant or who may become pregnant.
When cleaning any spills of bodily fluid, use only disposable cleaning cloths that can be flushed down a toilet. Ask your doctor or health department how to dispose of any bodily fluid spills that cannot be flushed down a toilet.
To protect others from exposure to the radioactive matter in your body, try to stay at least 6 feet away from other people, especially children or pregnant women. Follow these steps for several days after your Tositumomab treatment ends:
- Avoid crowds and public places. Avoid traveling on long trips.
- Do not share a bed or bathroom with another person.
- Sit on the toilet while urinating and flush 3 times with the lid down after use.
- Always wash your hands after using the bathroom.
- Do not share a towel, wash cloth, or toothbrush with another person.
- Do not share drinking glasses, plates, or silverware.
- Wait at least 1 week before washing any of the clothing and bed or bath linens you have used during the week after your treatment. Keep these items separate from the laundry of other people in your home.
- Wash your clothing and other items separately from other laundry in your home.
Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.
Do not receive a "live" vaccine while using tositumomab. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.
Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.