Pronunciation:

ib-ri-TYOO-mo-mab tye-UX-e-tan

Brand Names:

• Zevalin In-111
• Zevalin Y-90

Dosage Forms:

• Solution

Warnings:

• Fatal Infusion Reactions
  • Deaths have occurred within 24 hours of rituximab infusion, an essential component of the ibritumomab tiuxetan therapeutic regimen. These fatalities were associated with an infusion reaction symptom complex that included hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Approximately 80% of fatal infusion reactions occurred in association with the first rituximab infusion. Patients who develop severe infusion reactions should have rituximab, In-111 ibritumomab tiuxetan, and Y-90 ibritumomab tiuxetan infusions discontinued and receive medical treatment.
• Prolonged and Severe Cytopenias
  • Y-90 ibritumomab tiuxetan administration results in severe and prolonged cytopenias in most patients. The ibritumomab tiuxetan therapeutic regimen should not be administered to patients with greater than or equal to 25% lymphoma marrow involvement and/or impaired bone marrow reserve.
• Severe Cutaneous and Mucocutaneous Reactions
  • Severe cutaneous and mucocutaneous reactions, some with fatal outcome, have been reported in association with the ibritumomab tiuxetan therapeutic regimen. Patients experiencing a severe cutaneous or mucocutaneous reaction should not receive any further component of the ibritumomab tiuxetan therapeutic regimen and should seek prompt medical evaluation.
• Dosing
  • The prescribed, measured, and administered dose of Y-90 ibritumomab tiuxetan should not exceed the absolute maximum allowable dose of 32 millicurie (1184 megabecquerels).
  • Y-90 ibritumomab tiuxetan should not be administered to patients with altered biodistribution as determined by imaging with In-111 ibritumomab tiuxetan.
• In-111 ibritumomab tiuxetan and Y-90 ibritumomab tiuxetan are radiopharmaceuticals and should be used only by physicians and other professionals qualified by training and experienced in the safe use and handling of radionuclides .

Fatal infusion reactions have occurred within 24 hours of rituximab infusion, an essential component of the ibritumomab tiuxetan therapeutic regimen. Approximately 80% of fatal infusion reactions occurred in association with the first rituximab infusion. Administration also results in severe and prolonged cytopenias in most patients. The ibritumomab tiuxetan therapeutic regimen should not be administered to patients with greater than or equal to 25% lymphoma marrow involvement and/or impaired bone marrow reserve. Severe cutaneous and mucocutaneous reactions, some with fatal outcome, have been reported in association with therapy. The prescribed, measured, and administered dose of Y-90 ibritumomab tiuxetan should not exceed the absolute maximum allowable dose of 32.0 millicurie (1184 megabecquerels) .

Classifications:

Therapeutic—

Antineoplastic Agent

Pharmacologic—

Monoclonal Antibody

Uses of This Medicine:

Ibritumomab tiuxetan is a protein called a monoclonal antibody. It is used along with another monoclonal antibody (rituximab) and two radioactive medications (In-111 and Y-90). Ibritumomab tiuxetan is used to treat a type of cancer called non-Hodgkin's lymphoma.

Ibritumomab tiuxetan is to be administered only by or under the immediate supervision of your doctor.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of ibritumomab tiuxetan in children. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of ibritumomab tiuxetan in the elderly.

Pregnancy—

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of ibritumomab tiuxetan. Make sure you tell your doctor if you have any other medical problems, or sensitivity or a previous severe allergic reaction to ibritumomab tiuxetan, rituximab, yttrium chloride, indium chloride or to mouse proteins.

Proper Use of This Medicine:

You will receive this medicine while you are in a hospital or cancer treatment center. A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed into one of your veins.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. Tell your doctor right away if you think you have become pregnant while using the medicine.

If you experience a severe skin reaction, you should stop receiving this treatment and seek medical attention immediately. Symptoms may include blistering or loosening of skin; red, swollen, irritated, or scaly skin; fever, chills, headache, or diarrhea.

This medicine may cause a rare but serious type of allergic reaction. Tell your doctor right away if you start to have a cough; difficulty swallowing; dizziness; fast heartbeats; wheezing; trouble breathing; chest tightness; large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs; fever; chills; itching or hives; or lightheadedness or faintness while you are receiving this medicine.

While you are being treated with ibritumomab tiuxetan, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Ibritumomab tiuxetan may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine within the last several months. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Ibritumomab tiuxetan can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• Avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid sports or other situations where bruising or injury could occur.

If ibritumomab tiuxetan accidentally seeps out of the vein into which it is injected, it may damage some tissues and cause scarring. Tell the doctor or nurse right away if you notice redness, pain, or swelling at the place of injection.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Black, tarry stools

bleeding gums

blood in urine or stools

cough or hoarseness

coughing up blood

difficulty in breathing or swallowing

dizziness

fever or chills

headache

increased menstrual flow or vaginal bleeding

large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, sex organs

lower back or side pain

noisy breathing

nosebleeds

painful or difficult urination

pale skin

paralysis

pinpoint red spots on skin

prolonged bleeding from cuts

red stools

red or dark brown urine

shortness of breath

sore throat

sores, ulcers, or white spots on lips or in mouth

swollen glands

tightness in chest

troubled breathing with exertion

unusual bleeding or bruising

unusual tiredness or weakness

wheezing

Less common

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

pain at site of tumor

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 skin

unusual vaginal bleeding

vomiting blood or material that looks like coffee grounds

Rare

Agitation

anxiety

back pain

blurred vision

coma

drowsiness

fast, pounding, or irregular heartbeat or pulse

hallucinations

inability to speak

irritability

mood or mental changes

nausea

redness of skin

seizures

severe headache

slurred speech

stiff neck

temporary blindness

vomiting

weakness in arm and/or leg on one side of the body, sudden and severe

welts

Incidence not known

Blistering, peeling, loosening of skin

cracks in the skin

joint or muscle pain

loss of heat from the body

red irritated eyes

red skin lesions, often with a purple center

red, swollen skin

scaly skin

skin blisters

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Abdominal pain or stomach pain

bruising

constipation

difficult or labored breathing

difficulty in moving

faintness or lightheadedness when getting up from a lying or sitting position

fear

feeling of warmth

full or bloated feeling or pressure in the stomach

joint pain

lack or loss of strength

large, flat, blue or purplish patches in the skin

loss of appetite

muscle aching or cramping

muscle pain or stiffness

nervousness

pain

pain in joints

rash

redness of the face, neck, arms and occasionally, upper chest

runny nose

sleeplessness

sneezing

stuffy nose

sudden or increased sweating

swelling of abdominal or stomach area

swelling of hands, ankles, feet, or lower legs

swollen joints

throat irritation

trouble sleeping

unable to sleep

weight loss

Less common

Acid or sour stomach

belching

heartburn

indigestion

stomach discomfort, upset, or pain

swelling or redness in joints

For several months after receiving this therapy, it may still produce some side effects that need attention. During this period of time check with your doctor immediately if you notice any of the following:

Bleeding gums

blurred vision

bone pain

chills

confusion

cough

coughing up blood

difficulty in breathing or swallowing

dizziness

fainting

fast heartbeat

fever

headache, sudden and severe

inability to speak

increased menstrual flow or vaginal bleeding

lightheadedness

lower back or side pain

nosebleeds

painful or difficult urination

pale skin

paralysis

prolonged bleeding from cuts

rapid, shallow breathing

red or black, tarry stools

red or dark brown urine

seizures

shallow breathing

shortness of breath

slurred speech

sore throat

temporary blindness

ulcers, sores, or white spots in mouth

unusual bleeding or bruising

unusual tiredness or weakness

weakness in arm and/or leg on one side of body, sudden and severe

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.