Ibritumomab – Uses, Dosage, Side Effects, Interaction

Ibritumomab tiuxetan is a monoclonal anti-CD20 antibody used to treat B-cell non-Hodgkin lymphoma via a conjugated radioactive isotope. Indium or yttrium conjugated murine IgG1 kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Ibritumomab is produced in Chinese hamster ovary cells and is composed of two murine gamma 1 heavy chain of 445 amino acids each and two kappa light chains of 213 amino acids each.

Mechanism of action

The Fab segment of the antibody targets the CD20 epitope on B-cells, allowing the radioactive yttrium to destroy the cell via the production of beta particles.

Binding observed on lymphoid cells of the bone marrow, lymph node, thymus, red and white pulp of the spleen, lymphoid follicles of the tonsil, and lymphoid nodules of other organs (e.g., large and small intestines)

The antibody binds to the CD20 antigen found on the surface of normal and malignant B cells (but not B cell precursors), allowing radiation from the attached isotope (mostly beta emission) to kill it and some nearby cells. In addition, the antibody itself may trigger cell death via antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis. Together, these actions eliminate B cells from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells.[rx]

Indications

  • Ibritumomab is used to treat relapsed or refractory, low-grade or transformed B cell non-Hodgkin’s lymphoma (NHL), a lymphoproliferative disorder, and previously untreated follicular NHL in adult patients who achieve a partial or complete response to first-line chemotherapy.[rx] The treatment should not be administered to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve
  • For the treatment of non-Hodgkin’s lymphoma
  • Follicular Non-Hodgkin’s Lymphoma
  • Follicular Non-Hodgkin’s Lymphoma Refractory
  • Relapsed follicular B-cell non-Hodgkin’s lymphoma

Contraindications

  • decreased function of bone marrow
  • increased risk of bleeding due to clotting disorder
  • decreased blood platelets
  • low levels of a type of white blood cell called neutrophils
  • pregnancy
  • a patient who is producing milk and breastfeeding
  • a bad infection
  • significantly decreased activity of the bone marrow
  • anemia
  • bleeding
  • pregnancy

Dosage

Strengths: 3.2 mg/2 mL

Non-Hodgkin’s Lymphoma

Day 7, 8, or 9 following initial rituximab infusion:

  • Within 4 hours of rituximab, administer Y-90 ibritumomab 0.4 mCi/kg (14.8 MBq/kg) actual body weight intravenously over 10 minutes for patients with normal platelet count (Platelet count greater than 150,000/mm3).
  • Maximum dose: 32 mCi (1184 MBq) Y-90 ibritumomab dose regardless of actual body weight.
  • Do not treat if platelets less than 100,000/mm3
  • Initiate the regimen following recovery of platelet counts to at least 150,000/mm3 at least 6 weeks, but not more than 12 weeks, following the last dose of first-line chemotherapy

Dose Adjustments

  • Platelet count between 100,000/mm3 and 149,000/mm3 (in relapsed or refractory patients): Y-90 ibritumomab 0.3 mCi/kg (11.1 MBq/kg) actual body weight intravenously over 10 minutes

Administration advice:

  • Administer Y-90 ibritumomab through a free-flowing intravenous line.
  • Use a 0.22 micron low-protein-binding in-line filter between the syringe and the infusion port.
  • After injection, flush the line with at least 10 mL normal saline.

Side Effects

The Most Common

  • nausea
  • vomiting
  • stomach pain or swelling
  • constipation
  • heartburn
  • loss of appetite
  • headache
  • anxiety
  • dizziness
  • difficulty falling asleep or staying asleep
  • back, joint, or muscle pain
  • flushing
  • redness, tenderness, or an open wound in the area where the medication was injected
  • redness, ulcers, or skin changes where the medicine was injected;
  • easy bruising, unusual bleeding, purple or red spots under your skin;
  • unusual weakness or tiredness;
  • low red blood cells (anemia)–pale skin, weakness, cold hands and feet; or
  • low white blood cell counts–fever, mouth sores, skin sores, sore throat, cough, trouble breathing.

More common

  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • cough or hoarseness
  • coughing up blood
  • difficulty with breathing or swallowing
  • dizziness
  • fever or chills
  • headache
  • increased menstrual flow or vaginal bleeding
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • lower back or side pain
  • noisy breathing
  • nosebleeds
  • painful or difficult urination
  • pale skin
  • paralysis
  • pinpoint red spots on the skin
  • prolonged bleeding from cuts
  • red or dark brown urine
  • red stools
  • shortness of breath
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swollen glands
  • tightness in the chest
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • wheezing

Rare

  • Bloody nose that does not stop after pinching the nose together and holding it for 5 to 10 minutes
  • bluish lips or skin
  • chest pain or discomfort
  • confusion
  • diarrhea
  • fainting
  • fast heartbeat
  • hives
  • itching
  • lightheadedness
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • rapid, shallow breathing
  • skin rash
  • small red or purple spots on the skin
  • unusual vaginal bleeding
  • vomiting blood or material that looks like coffee grounds
  • Agitation
  • anxiety
  • back pain
  • bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, or warmth at the injection site
  • blurred vision
  • coma
  • drowsiness
  • fast, pounding, or irregular heartbeat or pulse
  • hallucinations
  • inability to speak
  • irritability
  • mood or mental changes
  • nausea
  • redness of the skin
  • seizures
  • severe headache
  • slurred speech
  • stiff neck
  • temporary blindness
  • vomiting
  • weakness in the arm or leg on one side of the body, sudden and severe
  • welts
  • Blistering, peeling, or loosening of the skin
  • cracks in the skin
  • joint or muscle pain
  • loss of heat from the body
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • red, swollen skin
  • scaly skin
  • skin blisters

Drug Interactions

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Pregnancy and Lactation

US FDA pregnancy category: Unassigned

Pregnancy

This drug may cause fetal harm when administered to a pregnant woman. Potential fetal risk should be considered and informed if pregnancy occurs while receiving treatment with this drug. Encourage male and female patients to use adequate methods of contraception during and for a minimum of 12 months following treatment. Pregnancy testing in females should be conducted prior to treatment.

Lactation

  • Use should be avoided during treatment, and for 6 months after the last dose. According to some authorities, the use during lactation is contraindicated.
  • Excreted into human milk: Unknown
  • Excreted into animal milk: Unknown
  • There is no information regarding this drug on its presence in human milk, its effects on a breastfed infant, or its effects on milk production.

How should this medicine be used?

Ibritumomab injection comes as a liquid to be injected into a vein over 10 minutes by a doctor who has been trained to treat patients with radioactive medication. It is given as part of a specific cancer treatment regimen. On the first day of the treatment regimen, a dose of rituximab is given and the first dose of ibritumomab injection is given no more than 4 hours afterward. Imaging scans to see how ibritumomab injection has spread through the body are performed 48 to 72 hours after the dose of ibritumomab injection is given. Additional scans may be performed if needed during the next several days. If the results of the scan(s) show that the ibritumomab injection has spread through the body as expected, the second dose of rituximab and a second dose of ibritumomab injection will be given 7 to 9 days after the first doses were given.

What special precautions should I follow?

Before receiving an ibritumomab injection,

  • tell your doctor and pharmacist if you are allergic to ibritumomab, any of the medications mentioned in the IMPORTANT WARNING section, any other medications, or any of the ingredients in ibritumomab injection. Ask your doctor or pharmacist for a list of the ingredients.
  • tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor if you have or have ever had any medical condition.
  • tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while you are receiving ibritumomab. If you are female, you will need to take a pregnancy test before starting treatment and use birth control to prevent pregnancy during your treatment and for 12 months after your final dose. If you are a male with a female partner, use birth control to prevent pregnancy during your treatment and for 12 months after your final dose. If you or your partner become pregnant while receiving ibritumomab injection, call your doctor immediately. Ibritumomab injection may harm the fetus.
  • tell your doctor if you are breastfeeding or plan to breastfeed. You should not breastfeed while receiving ibritumomab and for 6 months after your final dose.
  • you should know that this medication may decrease fertility in men and women. Talk to your doctor about the risks of receiving ibritumomab.
  • if you are having surgery, including dental surgery, tell the doctor or dentist that you have received ibritumomab injection.
  • do not have any vaccinations during treatment and for 12 months after your final dose without first talking to your doctor.
  • you should know that the radioactivity in the second dose of ibritumomab injection may be present in your body fluids for up to a week after you receive the dose. To prevent the radioactivity from spreading to people who are in close contact with you, you should be sure to wash your hands thoroughly after using the bathroom, use a condom every time you have sexual intercourse, and avoid deep kissing. Follow these precautions during your treatment and for 7 days after you receive your second dose of ibritumomab injection.
  • you should know that ibritumomab injection contains albumin (a product that is made from live donor blood). Although there is an extremely small chance that viruses may be spread through the blood, no cases of viral diseases from this product have been reported.
  • you should know that if you receive ibritumomab injection, your body may develop antibodies (substances in the blood that help the immune system recognize and attack foreign substances) to murine proteins. If you develop these antibodies, you may have an allergic reaction when you take medications made from murine proteins, or these medications might not work well for you.After your treatment with ibritumomab injection, be sure to tell all of your doctors that you have been treated with ibritumomab injection.

 

References