Tositumomab

(toss-sit-too-moh-mab)

Trade/other name(s): Bexxar

Why would this drug be used?

This drug is used to treat certain types of non-Hodgkin lymphoma.

How does this drug work?

Tositumomab is a type of radioimmunotherapy agent. It is a monoclonal antibody that is joined to a radioactive substance called iodine-131, or I-131. (A monoclonal antibody is a man-made version of an immune system protein that can only link to one special receptor site.)

Tositumomab is designed to seek out and lock onto a certain receptor (CD20) located on B lymphocytes (B cells) in the body. The cancerous B cells of non-Hodgkin lymphoma carry this protein, as do some normal B cells. Tositumomab is like a "smart bomb" in that it delivers the radiation to one type of cell. Both the antibody itself and the radioactive I-131 to which it is attached can act to kill the cancer cells.

Before taking this medicine

Tell your doctor…

• If you are allergic to anything, including medicines, dyes, additives, foods, or to iodine.
• If you have ever had a drug made with mouse proteins, especially if you reacted to it. You may be more likely to react to this drug.
• If you have any medical conditions such as kidney disease, liver disease (including hepatitis), heart disease, congestive heart failure, diabetes, gout, or infections. These conditions may require that your medicine dose, regimen, or timing be changed.
• If you are pregnant, trying to get pregnant, or if there is any chance of pregnancy. This drug may cause birth defects if either the male or female is taking it at the time of conception or during pregnancy. Men and women who are taking this drug should use some kind of birth control during treatment and for 12 months afterward. Check with your doctor about what kinds of birth control can be used with this medicine.
• If you are breast-feeding. The drug passes into breast milk and may affect the baby. Women should stop breast feeding before treatment with this drug.
• If you think you might want to have children in the future. This drug may reduce fertility. Talk with your doctor about the possible risk with this drug and the options that may preserve your ability to have children.
• About any other prescription or over-the-counter medicines you are taking, including vitamins and herbs. In fact, keeping a written list of each of these medicines (including the doses of each and when you take them) with you in case of emergency may help prevent complications if you get sick.

Interactions with other drugs

Any drugs or supplements that interfere with blood clotting can raise the risk of bleeding during treatment with tositumomab. These include:

• vitamin E
• non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn), and many others
• warfarin (Coumadin)
• ticlopidine (Ticlid)
• clopidogrel (Plavix)

Note that many cold, flu, fever, and headache remedies contain aspirin or ibuprofen. Ask your pharmacist if you aren't sure what is in the medicines you take.

No other serious interactions are known at this time. But this does not necessarily mean that none exist. Check with your doctor, nurse, or pharmacist about your other medicines, herbs, and supplements, and whether alcohol can cause problems with this medicine.

Interactions with foods

No serious interactions with food are known at this time. Check with your doctor, nurse, or pharmacist about whether some foods may be a problem.

Tell all the doctors, dentists, nurses, and pharmacists you visit that you are taking this drug.

How is this drug taken or given?

Tositumomab is injected into a vein. The dose depends how long the radioactivity will stay in your body. To figure this out, a test dose is given, and you will get imaging scans each day for 3 days. About a week later, the treatment dose is given in 2 injections in a vein. The first shot, an antibody, is given over an hour, then the second shot, an antibody plus radioactive iodine, is given a few minutes later.

Your doctor or nurse will likely give you medicine before you get the drug to try to prevent an allergic reaction.

At least 24 hours before you get the test dose, you will need to start taking iodine drops or tablets to help protect your thyroid from the radioactivity. Take the iodine exactly as your doctor prescribes, both during treatment and for 2 weeks afterward. If you have questions or don't understand the instructions, talk to your doctor or nurse.

Precautions

This drug can cause allergic reactions in some people, especially with the first treatment. Mild reactions usually consist of fever and chills. More serious reactions happen rarely, but can be dangerous. Symptoms can include feeling lightheaded or dizzy (due to low blood pressure), fever or chills, hives, nausea, itching, headache, coughing, trouble breathing or swallowing, fast breathing, tightness in the throat, or swelling of the face, tongue, or eyes. Tell your doctor or nurse right away if you notice any of these symptoms during or in the first couple of days after getting the drug.

Many people get mild symptoms in the first few days after receiving the treatment, including headache, fever, nausea, abdominal pain, feeling "blah" and without energy, and feeling tired. Talk with your doctor or nurse about what to do for these symptoms.

Your doctor will likely test your blood before, during, and for some weeks after your treatment, looking for possible effects of the drug on blood counts (described below) or on other body organs. Based on the test results, you may be given medicines to help treat any effects. Keep all your appointments for lab tests and doctor visits.

This drug can lower your white blood cell count, especially in the weeks after the drug is given. This can increase your chance of getting an infection. Be sure to let your doctor or nurse know right away if you have any signs of infection, such as fever (100.5° or higher), chills, pain when passing urine, new cough, or bringing up sputum.

This drug may lower your platelet count in the weeks after it is given, which can increase your risk of bleeding. Speak with your doctor before taking any drugs or supplements that might affect your body's ability to stop bleeding, such as aspirin or aspirin-containing medicines, warfarin (Coumadin), or vitamin E. Tell your doctor right away if you have unusual bruising, or bleeding such as nosebleeds, bleeding gums when you brush your teeth, or black, tarry stools.

This drug may lower your red blood cell count. If this occurs, it is usually a few weeks after starting treatment. A low red blood cell count (known as anemia) can cause shortness of breath, or make you feel weak or tired all the time. Your doctor may give you medicines to help prevent or treat this condition, or you may need to get blood transfusions.

Do not get any immunizations (vaccines), either during or after treatment with this drug, without your doctor's OK. Tositumomab may affect your immune system. This could make vaccinations ineffective, or even lead to serious infections if you get certain vaccines during treatment or for some time afterward. Try to avoid contact with people who have recently received a live virus vaccine, such as the oral polio vaccine or smallpox vaccine. Check with your doctor about this.

The iodine portion of this drug may cause your thyroid gland to stop working as it should, which could lead to a condition called hypothyroidism. You will be given an iodine supplement by mouth during your treatments to help block the drug's effect on the thyroid gland. Still, your doctor will check your thyroid hormone levels during and after treatment to monitor your thyroid function. You will need tests each year for the rest of your life to check your thyroid. If it stops making enough thyroid hormone, the doctor will prescribe pills for you to take every day.

You will receive a small amount of radiation when getting this drug. Your doctor or nurse will explain what precautions you should take to minimize the risk of radiation exposure to others.

Because of the way this drug acts on cells in the body, it may increase your long-term risk of getting a second type of cancer, such as leukemia, myelodysplastic syndrome, or solid tumors. This is rare, but if it does occur it would likely be years after the drug is used. If you are getting this drug, your doctor feels this risk is outweighed by the risk of what might happen if you do not get this drug. You may want to discuss these risks with your doctor.

Both men and women should avoid conceiving a child for at least 12 months after treatment in order to prevent harm to the fetus. Talk with your doctor about what kind of birth control you can use with this medicine.

Some people who get drugs that contain mouse proteins, such as tositumomab, may develop antibodies to these proteins. This increases the risk of allergic reactions to future tests or treatments that include mouse proteins. It also means that certain lab tests that depend on mouse antibodies will give inaccurate results (for example, some types of CA-125 tests).

Possible side effects

You will probably not have most of the following side effects, but if you have any talk to your doctor or nurse. They can help you understand the side effects and cope with them.

Common

• mild reaction, such as fever, chills, and sweating during or within the first few days after treatment*
• feeling tired or "blah"*
• stomach problems, such as nausea, vomiting, diarrhea, and pain in the abdomen (belly)
• low white blood cell count with increased risk of infection*
• low platelet count with increased risk of bleeding*
• low red blood cell count with increased risk of anemia*

Less common

• low thyroid function (hypothyroidism), which may happen right away or years later*
• poor appetite
• muscle or body aches and pain
• rash*
• itching*
• infection*

Rare

• severe allergic reaction with rash, hives, fever and chills, swelling of face or lips, and trouble breathing (during or within 48 hours after the medicine is given)*
• development of a second cancer (usually years later)*
• death due to allergic reaction, infection, or other causes

*See the Precautions section for more detailed information.

There are other side effects not listed above that can also occur in some patients. Tell your doctor or nurse if you develop these or any other problems.

FDA approval

Yes – first approved in 2003.

Disclaimer: This information does not cover all possible uses, actions, precautions, side effects, or interactions. It is not intended as medical advice, and should not be relied upon as a substitute for talking with your doctor, who is familiar with your medical needs.