Unituxin

Unituxin is a prescription medication used to treat high-risk neuroblastoma, a rare type of cancer that affects infants and young children. Unituxin is a monoclonal antibody that works by using the immune system to target and destroy tumor cells.

Unituxin comes in a liquid to be given by intravenous (IV) injection over a period of 10 to 20 hours for 4 days in a row. It may be given for up to 5 cycles.

Common side effects include pain, fever and low blood platelet counts.

Do not use dinutuximab if you are pregnant.

Call your doctor at once if you have severe or worsening pain, numbness, tingling, weakness, or burning in your hands or feet, or if you have problems with walking or daily activities.

Some side effects may occur during the injection or up to 24 hours afterward. Tell your caregiver right away if you feel dizzy or light-headed, or if you have a skin rash, chest tightness, wheezing, trouble breathing, or swelling in your face.

You should not receive dinutuximab if you are allergic to it.

To make sure dinutuximab is safe for you, tell your doctor if you have:

• any type of bacterial, fungal, or viral infection;

• an eye disorder or vision problems;

• bone marrow suppression;

• low blood pressure;

• an electrolyte imbalance (such as low levels of potassium, sodium, or calcium in your blood);

• liver or kidney disease; or

• problems with urination.

Do not use dinutuximab if you are pregnant. It could harm the unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 2 months after your treatment ends.

It is not known whether dinutuximab passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Distribution

Extent

Not known whether dinutuximab is distributed into milk.1

Elimination

Half-life

10 days.1

• Risk of serious infusion-related reactions and anaphylaxis.1 Importance of informing clinician immediately if signs and symptoms of such reactions (e.g., facial swelling, urticaria, breathing difficulty, lightheadedness or dizziness) occur during or within 24 hours of dinutuximab infusion.1

• Risk of severe pain and peripheral sensory and motor neuropathy.1 Importance of promptly informing clinician if severe or worsening pain or signs and symptoms of neuropathy (e.g., numbness, tingling, burning, weakness) occur.1

• Risk of capillary leak syndrome.1 Importance of informing clinician immediately if signs and symptoms of capillary leak syndrome (e.g., hypotension, generalized edema, dyspnea) occur.1 5

• Risk of hypotension during dinutuximab infusion.1 Importance of informing clinician immediately if signs and symptoms of hypotension occur.1

• Risk of infection.1 Importance of informing clinician immediately if signs and symptoms of infection occur.1

• Risk of adverse ocular effects.1 Importance of promptly informing clinician if signs and symptoms of ocular toxicity (e.g., blurred vision, photophobia, ptosis, diplopia, unequal pupil size) occur.1

• Risk of myelosuppression.1 Importance of promptly informing clinician if signs and symptoms of anemia, thrombocytopenia, or infection occur.1

• Risk of electrolyte abnormalities (i.e., hypokalemia, hyponatremia, hypocalcemia).1 Importance of informing clinician if signs and symptoms of electrolyte abnormalities (e.g., seizures, palpitations, muscle cramping) occur.1

• Risk of atypical hemolytic uremic syndrome.1 Importance of informing clinician if signs and symptoms of hemolytic uremic syndrome (e.g., fatigue, dizziness, fainting, pallor, edema, decreased urination, hematuria) occur.1

• Risk of fetal harm.1 Necessity of advising women of childbearing potential to use an effective method of contraception while receiving the drug and for ≥2 months after discontinuance of therapy.1 If pregnancy occurs, advise pregnant women of potential risk to the fetus.1

• Importance of not breast-feeding during therapy.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Your doctor will check your progress closely while you are receiving this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you or your child should continue to receive it. 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 during treatment and for 2 months after the last dose of this medicine. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine may cause a rare but serious type of an allergic reaction called an infusion reaction. This can be life-threatening and require immediate medical attention. Tell your doctor right away if you or your child start to have cough, trouble breathing, hives, itching, or skin rash, lightheadedness, dizziness, or fainting, tightness in the chest, or swelling of the face or lips.

Check with your doctor right away if you or your child are having burning, numbness, tingling, or painful sensations in the arms, hands, legs, or feet. These could be symptoms of a condition called peripheral neuropathy.

Tell your doctor right away if you or your child have a cloudy urine, change in the amount of urine, fainting or lightheadedness, nausea, stomach pain, or swelling of the hands, ankles, or feet after receiving this medicine. These may be symptoms of a rare but serious condition called capillary leak syndrome.

This medicine could lower your blood pressure too much and cause you to feel dizzy or lightheaded. Stand or sit up slowly if you are dizzy. Low blood pressure is more likely to happen when you begin to use the medicine.

This medicine may cause reversible posterior leukoencephalopathy syndrome (RPLS). Tell your doctor if you have severe headache, changes in vision, fast, pounding, or uneven heartbeat, seizures, unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness.

Check with your doctor immediately if blurred vision, difficulty in reading, or any other change in vision occurs during or after treatment. Your doctor may want you or your child to have your eyes checked by an ophthalmologist (eye doctor).

Dinutuximab 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:

• If you can, avoid people with infections. Check with your doctor immediately if you or your child 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 the 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 contact sports or other situations where bruising or injury could occur.

Tell your doctor right away if you or your child have black, tarry stools, blood in the urine, fever, increased or decreased urination, pinpoint red spots on the skin, stomach pain, swelling of the face, fingers, feet, or lower legs, unusual bleeding, bruising, or weakness, or yellow eyes or skin after receiving this medicine. These may be symptoms of hemolytic uremic syndrome.

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:

• Black, tarry, stools
• bleeding gums
• blood in the urine or stools
• blurred vision
• chills
• cloudy urine
• coma
• confusion
• convulsions
• cough or hoarseness
• decrease or increase in the amount of urine
• difficult or labored breathing
• dizziness
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• fainting or lightheadedness
• fast or irregular heartbeat
• fever
• headache
• hives or welts, itching, or skin rash
• increased thirst
• irregular heartbeat
• loss of appetite
• lower back or side pain
• muscle pain or cramps
• nausea or vomiting
• noisy breathing
• numbness or tingling in the hands, feet, or lips
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• redness of the skin
• sore throat
• stomach pain
• sweating
• swelling of the face, hands, ankles, feet, or lower legs
• tightness in the chest
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unusual bleeding or bruising
• unusual tiredness or weakness

• Back pain
• bigger, dilated, or enlarged pupils (black part of the eye)
• burning, numbness, tingling, or painful sensations
• change in color vision
• change in the ability to see colors, especially blue or yellow
• chest pain
• difficulty seeing at night
• drooping upper eyelids
• increased sensitivity of the eyes to sunlight
• muscle or joint pain
• nerve pain
• pain in the arms or legs
• unsteadiness or awkwardness
• weakness in the arms, hands, legs, or feet

• Yellow eyes or skin

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:

• Diarrhea

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.

Unituxin (dinutuximab) is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2) and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy [see Clinical Studies (14)].

Unituxin (dinutuximab) is a chimeric monoclonal antibody composed of murine variable heavy and light chain regions and the human constant region for the heavy chain IgG1 and light chain kappa. Unituxin binds to the glycolipid disialoganglioside (GD2). Dinutuximab is produced in the murine myeloma cell line, SP2/0.

Unituxin is a sterile, preservative-free, clear/colorless to slightly opalescent solution for intravenous infusion. Unituxin is supplied in single-use vials of 17.5 mg/5 mL. Each vial contains 3.5 mg/mL of dinutuximab, histidine (20 mM), polysorbate 20 (0.05%), sodium chloride (150 mM), and water for injection; hydrochloric acid is added to adjust pH to 6.8.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No animal studies have been conducted to evaluate the carcinogenic or mutagenic potential of dinutuximab.

Dedicated studies examining the effects of dinutuximab on fertility in animals have not been conducted. No clear effects on reproductive organs were observed in general toxicology studies conducted in rats.

Animal Toxicology and/or Pharmacology

Non-clinical studies suggest that dinutuximab-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of CDC and ADCC activity.