Tositumomab and iodine I 131 tositumomab

What is Tositumomab and iodine I 131 tositumomab?

• Tositumomab and iodine I 131 tositumomab (Bexxar) is the combination of a monoclonal antibody to CD20 and iodine-131 which is used to treat refractory, advanced non-Hodgkin lymphoma.
• Tositumomab is a murine IgG2a lambda monoclonal antibody directed against the CD20 antigen, produced in mammalian cells.
• I-131 tositumomab is tositumomab covalently linked to Iodine-131.

Bexxar Automated-Inspection Unit (14678902565)

What are the uses of this medicine?

• Tositumomab and iodine I 131 tositumomab (Bexxar) is used 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.

Limitations of use:

• The Bexxar therapeutic regimen is only indicated for a single course of treatment.
• The safety and efficacy of additional courses of the Bexxar therapeutic regimen have not been established.
• The Bexxar therapeutic regimen is not indicated for first-line treatment of patients with CD20-positive non-Hodgkin's lymphoma.

How does this medicine work?

• Tositumomab and iodine I 131 tositumomab A murine IgG2a lambda monoclonal antibody, both unradiolabeled and radiolabeled with iodine I 131, directed against the human B cell-specific surface antigen CD20.
• Tositumomab binds to CD20, resulting in complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and apoptosis in B cells expressing CD20; in addition to the antibody-mediated cytotoxicity, iodine I 131 tositumomab delivers cytotoxic ionizing radiation specifically to CD20-expressing B cells.
• In a two-step therapeutic regimen, a predose of unradiolabeled tositumomab is administered first followed by the administration of a dosimetric dose of iodine I 131 tositumomab; 7-14 days later, a therapeutic dose of iodine I 131 tositumomab is administered.
• The predose of unradiolabeled tositumomab binds to nontumor B cells, increasing the terminal half-life of radiolabeled antibody while protecting nontumor B cells from radiolabeled antibody-mediated radiocytotoxicity.

Who Should Not Use this medicine ?

• This medicine have no usage limitations.

What drug interactions can this medicine cause?

• Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Is this medicine FDA approved?

• Following a first investigational new drug application in 1989 and biologics license application in 2000, Bexxar was approved by the FDA in 2003.
• Because of declining use and the availability of other anti-CD20 monoclonal antibodies, however, tositumomab was discontinued by its sponsor in 2014.

How should this medicine be used?

Recommended dosage:

• The Bexxar therapeutic regimen consists of 2 separate components (tositumomab and iodine I 131 tositumomab) administered in 2 separate steps (dosimetric dose and therapeutic 42 dose) separated by 7 to 14 days.

Administration:

• Do not administer the therapeutic dose if biodistribution is altered.
• Premedicate with oral diphenhydramine 50 mg and oral acetaminophen 650 mg 30 minutes prior to initiation of the therapeutic dose.
• Administer 450 mg tositumomab in 50 mL 0.9% sodium chloride by intravenous infusion through a 0.22 micron in-line filter over 60 minutes (refer to Site Training Manual for diagram
• showing assembly of the infusion set components). Decrease the rate of infusion by 50% for mild to moderate infusion reactions.
• Attach the shielded syringe containing the I-131 tositumomab dose in a syringe pump to the intravenous line containing the in-line filter used in step 2 above. A change in filter can result in loss of up to 7% of the I-131 tositumomab dose. Set syringe pump to deliver the entire dose of I-131 tositumomab over 20 minutes,
• immediately following completion of the tositumomab infusion. Decrease the rate of infusion by 50% for mild to moderate infusion reactions.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection, for intravenous infusion

This medicine is available in fallowing brand namesː

• Bexxar

What side effects can this medication cause?

The most common side effects of this medicine include:

• neutropenia
• thrombocytopenia
• anemia
• infections
• infusion reactions
• asthenia
• fever
• nausea

What special precautions should I follow?

• Hematological and non-hematological secondary malignancies have been reported.
• The Bexxar therapeutic regimen can cause hypothyroidism. Thyroid-blocking medication is required prior to administration of the Bexxar therapeutic regimen. Evaluate for clinical evidence of hypothyroidism and thyroid-stimulating hormone (TSH) level before treatment and annually thereafter.
• Administration to a pregnant woman can cause embryo-fetal harm including severe, and possibly irreversible, neonatal hypothyroidism. Females and males of reproductive potential should use effective contraception to avoid pregnancy
• during treatment and for 12 months after the therapeutic dose.
• The Bexxar therapeutic regimen can cause severe, including fatal, allergic reactions. Premedicate with acetaminophen and diphenhydramine. Permanently, discontinue the Bexxar therapeutic regimen in patients who develop serious allergic reactions.
• Patients receiving the Bexxar therapeutic regimen experienced severe and prolonged neutropenia, thrombocytopenia , and anemia.
• The Bexxar therapeutic regimen contains Iodine-131. Advise patients of the risks of radiation exposure of household contacts, pregnant women, and small children and of the steps to be taken to reduce these risks.
• Do not administer live viral vaccines to patients recently treated with Bexxar.
• Because of the potential for serious adverse reactions in nursing infants from the Bexxar therapeutic regimen, advise women to discontinue nursing or to consider alternative treatment.

What to do in case of emergency/overdose?

Symptoms of overdose may include:

• cytopenias

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.

Can this medicine be used in pregnancy?

• Pregnancy: Category D
• Administration of the Bexxar therapeutic regimen to a pregnant woman can cause fetal harm including severe and possibly irreversible neonatal hypothyroidism.
• Inform patients who are pregnant or become pregnant after the Bexxar therapeutic regimen about the potential hazard to a fetus.

Can this medicine be used in children?

• The safety and effectiveness of the Bexxar therapeutic regimen have not been established in children.

What are the active and inactive ingredients in this medicine?

Active Ingredients:

• Tositumomab
• I-131 tositumomab

Inactive Ingredients:

• ascorbic acid
• maltose
• povidone
• sodium chloride

Who manufactures and distributes this medicine?

• GlaxoSmithKline
• Research Triangle Park, NC

• Bexxar is a registered trademark of GlaxoSmithKline.

What should I know about storage and disposal of this medication?

Tositumomab:

• Store vials (including diluted vials) of tositumomab (35 mg and 225 mg) at 36o F to 46o F (2oC to 8o 673 C).
• Protect from strong light.
• Do not shake; do not freeze.
• Diluted tositumomab solutions are stable for up to 24 hours when stored refrigerated and for up to 8 hours at room temperature.
• Discard unused portions.

I-131 tositumomab:

• Store vials of I-131 tositumomab in the original lead pot at a temperature of -4o 677 F (-20°C) or below until thawed prior to administration.
• Thawed dosimetric and therapeutic doses of I-131 tositumomab (including diluted vials) are stable for up to 8 hours at 36°F to 46°F (2°C to 8°C) or at room temperature. I-131 tositumomab does not contain a preservative.
• Do not shake; do not freeze.
• Discard unused portions according to federal and state laws regarding radioactive and biohazardous waste.

• Dailymed label info on Tositumomab and iodine I 131 tositumomab
• FDA Tositumomab and iodine I 131 tositumomab