Ibritumomab – Uses, Dosage, Side Effects, Interaction

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

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.