Bexxar Therapy: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

BEXXAR^® therapy (tositumomab and iodine I 131 tositumomab) is indicated for:

• the treatment of patients with CD20 positive relapsed or

  refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with rituximab-refractory non-Hodgkin’s lymphoma.

This product should be administered under the supervision of a qualified health professional who is appropriately qualified in the use of radioimmunotherapy and the management of patients with non-Hodgkin’s lymphoma (NHL). Appropriate management of therapy and complications is only possible when adequate diagnostic and treatment facilities are readily available.

What it does:

BEXXAR^® therapy is considered a dual action treatment for non-Hodgkin’s lymphoma because it attacks cancer cells in two ways, providing both radiation therapy and immunotherapy in a single treatment. That’s why BEXXAR^® is called radioimmunotherapy.

The immunotherapy action of BEXXAR^® is provided by a monoclonal antibody called tositumomab. Tositumomab seeks out and attaches to the CD20 antigen on the surface of non-Hodgkin’s lymphoma cells. The radiation therapy action of BEXXAR^® comes from a radioactive substance, called an isotope (a form of an element that is often radioactive), which is attached to the monoclonal antibody. The isotope in BEXXAR^® is iodine-131. When tositumomab binds to the cancer cells, iodine-131 releases radiation that kills the attached cells. Radiation may also reach tumor cells that the monoclonal antibody cannot attach to. This is called crossfire effect. Other cells may also receive beams of radiation from the isotope. Some of the normal cells nearby may be affected as well.

When it should not be used:

Do not take BEXXAR^® therapy if :

• you have a known hypersensitivity (serious allergic reaction) to “murine proteins” (proteins that come from mice)
• if you are allergic to any component of BEXXAR^®.
• if you have > 25% lymphoma involvement in your bone marrow, platelet count < 100 x 10⁹/L or neutrophil count < 1.5 x 10⁹/L.
• if you have impaired bone marrow.
• if you are pregnant.

What the medicinal ingredient is:

BEXXAR^® therapy is composed of a monoclonal antibody, tositumomab, and a radiolabeled monoclonal antibody, iodine I 131 tositumomab. The radiation component of BEXXAR^®, iodine-131, leaves your body through urine over about a week, so radiation does not build up and stay in your body.

What the important nonmedicinal ingredients are: The tositumomab formulation contains 10% (w/v) maltose, 145 mM sodium chloride, 10 mM phosphate, 17.5 mM potassium hydroxide, and Water for Injection, USP.

The iodine I 131 tositumomab formulation for dosimetric and therapeutic dosage forms contains 4.4%-6.6% (w/v) povidone, 1-2 mg/mL maltose (dosimetric dose) or 9-15 mg/mL maltose (therapeutic dose), 8.5-9.5 mg/mL sodium chloride, 1.22 mg/mL phosphoric acid, 1.05- 6.57 mg/mL potassium hydroxide, and 0.9-1.3 mg/mL ascorbic acid. The pH is approximately 7.0.

WARNINGS AND PRECAUTIONS

Serious Warnings and Precautions

Special requirements: BEXXAR^® therapy contains a radioactive component and should be administered only by physicians and other health care professionals qualified by training in the safe use and handling of therapeutic radionuclides.

Thyroid-blocking therapy must be started at least 24 hours before receiving the first (dosimetric) dose and continued for 14 days after the treatment (therapeutic) dose of BEXXAR^® to decrease the risk of hypothyroidism (when your thyroid loses some function). Your doctor should provide you with a prescription for medication. Make sure you take your prescription as directed by your doctor.

WARNINGS AND PRECAUTIONS

Serious Warnings and Precautions

Hypersensitivity Reactions (serious allergic reactions), including Anaphylaxis (a severe allergic reaction, that may be life threatening): Serious hypersensitivity reactions, including some with fatal outcome, have been reported with BEXXAR^®. Medications for the treatment of severe hypersensitivity reactions should be available for immediate use. Signs and symptoms of severe allergic reactions may include fever, chills, sweating, low blood pressure, shortness of breath, bronchospasm, and nausea and have been reported during or within 48 hours of infusion. Patients who develop severe hypersensitivity reactions should have infusions of BEXXAR^® discontinued and receive medical attention.

Prolonged and Severe Cytopenias (a reduction in the number of blood cells): The majority of patients who received BEXXAR^® experienced severe thrombocytopenia (a disorder in which the number of platelets (a type of blood cell) is abnormally low, sometimes associated with abnormal bleeding) and neutropenia (an abnormally low level of neutrophils (white blood cells) in the blood). BEXXAR^® should not be administered to patients with > 25% lymphoma marrow involvement, platelet count < 100 x 10⁹/L or neutrophil count < 1.5 x 10⁹/L and/or impaired bone marrow reserve.

Pregnancy: BEXXAR^® can cause fetal harm when administered to a pregnant woman.

BEFORE you receive BEXXAR^® talk to your doctor if:

• you are allergic to tositumomab, murine proteins (proteins

  that come from mice) or any other ingredient in BEXXAR^® (see What the important nonmedicinal ingredients are).

• you are having or planning to have any vaccinations.
• you are pregnant or could be pregnant.

• you are breast-feeding. You must not receive BEXXAR^®

  if you are breast-feeding.

Pregnancy

• Use a reliable method of contraception to avoid becoming

  pregnant while you’re being treated with BEXXAR^®, and for 12 months after your last treatment. There may be an increased risk of miscarriage up to a year following treatment with BEXXAR^®.

• Use of BEXXAR^® while pregnant can cause fetal harm.

  Severe and possibly irreversible hypothyroidism in infants may occur.

  Prolonged low blood cell counts

  BEXXAR^® may result in low blood cell counts that may last for an extended period of time (see SIDE EFFECTS AND WHAT TO DO ABOUT THEM). Patients with ≥ 25% of their bone marrow cells affected by lymphoma and/or patients whose bone marrow may have difficulty recovery from therapy should not receive BEXXAR^®.

  Hypothyroidism

  Patients who receive BEXXAR^® are at risk of losing some function of their thyroid (hypothyroidism). Your doctor will test how well your thyroid is working before you are given BEXXAR^®, as well as afterwards (every 6 months for the first 2 years and each year thereafter). Symptoms of hypothyroidism include: weakness, weight gain, brittle fingernails and/or hair, pale skin.

  In order to minimize your risk of hypothyroidism, remember to take your thyroid blocking medicine as directed.

  Secondary cancers

  A small percentage of cancer patients (approximately 3 in 100) participating in BEXXAR^® studies developed a second type of cancer involving blood cells. Most of these patients, however, had already received other cancer drugs, such as alkylating agents and/or topoisomerase inhibitors, that have already been shown to potentially cause secondary cancers. Therefore it is difficult to know whether BEXXAR^® itself contributes to the risk of developing a secondary cancer.

  Children

  The safety and effectiveness of BEXXAR^® in children have not been evaluated.

  Safety precautions after receiving BEXXAR^®

  The following measures should be taken by the patient for up to 2 weeks after receiving the radiopharmaceutical.

  Therapeutic dose:

  Avoidance of contact with infants, young children, and pregnant women. Sleeping in a separate bed (separated by a distance of at least 2 to 3 meters). Maintain an appropriate distance of 2 meters from others. Travel alone in a private automobile if possible, otherwise maintain as great a distance as possible between patient and driver. Toilet should be used instead of urinal. Toilet should be flushed several times after use. Separate laundry and eating utensils and wash items separately. Ask your Nuclear Medicine physician for more specific information.

INTERACTIONS WITH THIS MEDICATION

Make sure your doctor knows about other medications you

are taking, including those you can buy without a prescription as well as herbal and alternative medicines.

No formal drug-drug interaction studies have been performed. If you are taking blood thinners or other medications that interfere with blood clotting, your doctor will need to monitor your blood counts carefully during and after treatment with BEXXAR^®.

PROPER USE OF THIS MEDICATION

BEXXAR^® therapy is not self administered by an individual. It should be administered under the supervision of a health professional who is experienced in the use of biologics and radiopharmaceuticals.

Preparation before receiving treatment with BEXXAR^®

You must start your thyroid protective agent at least 24 hours before your first dose (Day 0) and continue until 2 weeks after your last dose of BEXXAR^®.

BEXXAR^® therapy

BEXXAR^® therapy consists of 4 components given in 2 discrete steps: the dosimetric step, followed 7-14 days later by a therapeutic step.

Step 1 – Dosimetric step

During your first visit (Day 0), you will:

• receive tositumomab (the monoclonal antibody) by

  intravenous infusion over 1 hour, then

• receive an intravenous infusion of iodine I 131

  tositumomab (radiolabeled monoclonal antibody) over 20 minutes

• have a whole body scan within an hour of the end of the

  intravenous infusion. You MUST NOT go to the bathroom (urinating) until AFTER this scan is done.

On your second visit (Day 2, 3 or 4), you will have a second whole body scan right after urinating.

On your third visit (Day 6 or 7), you will have another whole body scan right after urinating. These scans will help your doctor to determine your personalized dosing.

Step 2 – Therapeutic step

During your fourth visit (Day 7 or up to Day 14), you will:

• receive tositumomab by intravenous infusion over 1 hour,

  then

• receive an intravenous infusion of your personalized dose

  of iodine I 131 tositumomab over 20 minutes.

Follow-up after receiving BEXXAR^® therapy

Your blood cell counts will continue to be monitored every

week after completion of BEXXAR^® therapy until your blood counts have recovered (at least 8 weeks). Talk to your doctor for more details regarding your follow-up.

Overdose:

In case of overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

The premedications you are given before receiving BEXXAR^® may help control the most common side effects that some patients may experience, like fever, chills, and flu-like symptoms.

During infusions, your treatment team will monitor your blood pressure, heart rate, breathing, and temperature. If changes occur, your treatment team may decide to slow down or stop the infusion.

Most patients who receive BEXXAR^®, experience decreased blood counts. This decrease may last a number of weeks. During this time, you may be susceptible to serious infections. You may need to receive blood transfusions or medications that will help your counts recover faster. Please see the table for information on low white blood cells, platelets and red blood cells.

BEXXAR^® may cause reactions because it contains proteins not usually found in your body.

After you complete treatment and go home, be sure to call your oncologist or hematologist if any side effects get worse, or if you have any new side effects from the BEXXAR^® treatment.

Possible side effects with BEXXAR^® therapy are outlined in the table below.

As per Comment 5e

This is not a complete list of side effects. For any unexpected effects while taking BEXXAR^®, contact your doctor or pharmacist.

REPORTING SUSPECTED SIDE EFFECTS You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

-------------------------------------------------------------------------- $ Report online at www.healthcanada.gc.ca/medeffect $ Call toll-free at 1-866-234-2345

$ Complete a Canada Vigilance Reporting Form and:

• Fax toll-free to 1-866-678-6789, or

• Mail to: Canada Vigilance Program Health Canada

  Postal Locator 0701E Ottawa, Ontario

  K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect^™ Canada Web site at www.healthcanada.gc.ca/medeffect.

NOTE: Should you require information related to the management of side effects, contact your health professional. The Canada Vigilance Program does not provide medical advice.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found at:

http://www.gsk.com

or by contacting the sponsor, GlaxoSmithKline Inc at:

7333 Mississauga Road

Mississauga, Ontario

L5N 6L4

1-800-387-7374.

Visit

The Health Canada

Last revised:

^© 2013 GlaxoSmithKline Inc. All Rights Reserved ^® BEXXAR is used under license by GlaxoSmithKline Inc.