Pronunciation:

tis-a-jen-lek-LOO-sel

Brand Names:

• Kymriah

Dosage Forms:

• Suspension

Warnings:

Warning: Cytokine release syndrome and neurological toxicitiesCytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving tisagenlecleucel. Do not administer tisagenlecleucel to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.Neurological toxicities, which may be severe or life-threatening, can occur following treatment with tisagenlecleucel, including concurrently with CRS. Monitor for neurological events after treatment with tisagenlecleucel. Provide supportive care as needed.Tisagenlecleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the KYMRIAH REMS .

Classifications:

Therapeutic—

Antineoplastic Agent

Chemical—

CAR T-Cell Agent

Uses of This Medicine:

Tisagenlecleucel injection is used to treat B-cell acute lymphoblastic leukemia (ALL) that has come back a second or later time or after other medicines did not work well in patients up to 25 years of age. Leukemia is a type of cancer where the body makes abnormal white blood cells.

Tisagenlecleucel injection is also used to treat follicular lymphoma (FL) and large B-cell lymphoma (including diffuse large B-cell lymphoma [DLBCL], high grade B-cell lymphoma, or DLBCL from follicular lymphoma) that has come back or after 2 or more lines of treatment did not work well. Lymphoma is a type of cancer where the body makes abnormal white blood cells.

Tisagenlecleucel injection is an antineoplastic (cancer) medicine that is made from your own white blood cells, which have been modified to recognize and attack your cancer cells. Before you begin treatment, talk to your doctor about the benefits of this medicine as well as the possible risks of receiving it.

This medicine is available only under a restricted distribution program called Kymriah® REMS (Risk Evaluation and Mitigation Strategy) Program.

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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of tisagenlecleucel injection in children with ALL. Safety and efficacy have been established.

Appropriate studies have not been performed on the relationship of age to the effects of tisagenlecleucel injection in children with DLBCL and FL. Safety and efficacy have not been established.

Older adults—

Appropriate studies have not been performed on the relationship of age to the effects of tisagenlecleucel injection in the elderly. Safety and efficacy have not been established.

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 this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Heart problems or
• Hypotension (low blood pressure) or
• Infections (including hepatitis B), active or history of or
• Lung or breathing problems—Use with caution. May cause side effects to become worse.

• Neutropenia (low white blood cells) or
• Weak immune system—Use with caution. May increase risk for infection.

Proper Use of This Medicine:

A nurse or other trained health professional will give you this medicine in a hospital or cancer center. It is given through a needle placed into one of your veins. The medicine must be injected slowly, so your IV tube will need to stay in place for less than an hour. It is given 2 to 14 days (for ALL), 2 to 11 days (for DLBCL), or 2 to 6 days (for FL) after completing treatment with other cancer medicines (eg, fludarabine, cyclophosphamide, bendamustine).

You should stay within 2 hours of the office or center to check for unwanted effects for at least 4 weeks receiving this medicine.

It is very important that you understand the requirements of the Kymriah® REMS program, and become familiar with the Kymriah® medication guide. Read and follow these instructions carefully. Ask your doctor if you have any questions. Ask your pharmacist for the medication guide if you do not have one.

Missed dose—

This medicine needs to be given on a fixed schedule. If you miss a dose, call your doctor, home health caregiver, or treatment clinic for instructions.

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.

This medicine may cause cytokine release syndrome (CRS) and infusion reactions. This may be life-threatening and requires immediate attention. Tell your doctor right away if you or your child has a fever, chills, headache, nausea, lightheadedness, dizziness, fainting, skin rash, trouble breathing, or tiredness or weakness.

Check with your doctor right away if you or your child have seizures, loss of balance, loss of consciousness, confusion, disorientation, difficulty with speaking, or slurred speech. These may be symptoms of serious nerve problems.

This medicine may cause serious allergic reactions, including anaphylaxis, which can be life-threatening and require immediate medical attention. Talk to your doctor right away if you have very fast or irregular breathing, a very fast or irregular heartbeat, a rash, fainting, hive-like swellings on the skin, or swelling of the eyelids or around the eyes, face, lips, or tongue.

This medicine can temporarily lower the number of white blood cells in your blood, which increases the chance of getting an infection. If you can, avoid people with infections. Check with your doctor immediately if you think you or your child are getting an infection or if you have a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.

This medicine may increase your risks for hypogammaglobulinemia (immune system problem) and getting other cancers. Talk to your doctor if you have questions about these risks.

This medicine may cause dizziness, confusion, seizures, or decreased alertness. Do not drive or do anything else that could be dangerous until you know how this medicine affects you, for at least 8 weeks after treatment.

While you are being treated with tisagenlecleucel injection, do not have any immunizations (vaccinations) without your doctor's approval. Live virus vaccinations should not be given for at least 6 weeks before start of treatment, during treatment, and until recovery following the last cycle of this medicine.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

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 or nurse immediately if any of the following side effects occur:

More common

Agitation

back pain

bleeding gums

bloody urine

blue lips, fingernails, or skin

blurred vision

chest pain, discomfort, or tightness

chills

confusion as to time, place, or person

cough

coughing that sometimes produces a pink frothy sputum

coughing up blood

decreased urine output

depression

difficult, fast, noisy breathing

dilated neck veins

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

drowsiness

dry mouth

fast, pounding, or irregular heartbeat or pulse

fever

general feeling of discomfort or illness

hallucinations

headache

hoarseness

holding false beliefs that cannot be changed by fact

hostility

increase in heart rate

increased blood pressure

increased menstrual flow or vaginal bleeding

increased sweating

irritability

loss of appetite

loss of consciousness

lower back or side pain

mood or mental changes

muscle, joint, or bone pain

nausea

nervousness

nosebleeds

painful or difficult urination

pale skin

pounding in the ears

problems with speech or speaking

prolonged bleeding from cuts

rapid shallow breathing

rapid weight gain

red or black, tarry stools

red or dark brown urine

seeing, hearing, or feeling things that are not there

seizures

shakiness and unsteady walk

slow or fast heartbeat

stiff neck

sunken eyes

swelling of the face, arms, fingers, feet, or lower legs

trembling and shaking of hands

trouble breathing

unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

unusual excitement, nervousness, or restlessness

vomiting

weight gain

Less common

Change in the amount of urine

cloudy urine

headache, sudden or severe

stomach pain

tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area

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

Anxiety

decreased appetite

diarrhea

difficulty in moving

joint pain

muscle pain or stiffness

pain in the arms or legs

stuffy nose

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

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.