Crizotinib (Xalkori) is a type of cancer drug called a kinase inhibitor that is used to treat three rare forms of tumors.

Crizotinib is used to treat a type of non-small cell lung cancer (NSCLC) in people with an error in genes called ROS1 or ALK (anaplastic lymphoma kinase). An ROS1 error occurs in about 1 percent of people with NSCLC, while and ALK error occurs in about 5 percent of cases.

Defects in ROS1 and ALK cause cells to grow out of control causing cancer. Crizotinib works to help to stop or slow the growth of cancer. It does this by blocking the action of ROS1 and ALK and is known as a ROS1 tyrosine kinase inhibitor and an ALK tyrosine kinase inhibitor.

When Crizotinib was approved by the US Food and Drug Administration (FDA) in 2011, it was the first therapy to be approved for patients with ROS1-positive NSCLC.

Crizotinib is also used to treat a rare form of non-Hodgkin lymphoma (NHL) in children and young adults called anaplastic large cell lymphoma (ALCL) that has a defect in the ALK gene. About 90 percent of cases of ALCL in young people are ALK-positive.

Crizotinib is also used to treat children and adults with unresectable (unable to be removed by surgery), recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive. IMT is a type of tumor that forms in mucosal surfaces, which are found in your mouth, eyes, nose, digestive system, lungs and urinary and genital tracts. IMT also forms in mesentery, a type of tissue that connects the organs in your abdomen. IMT is usually benign (non-cancerous).

What is crizotinib used for?

Crizotinib is a prescription medicine that is used to treat:

• people with NSCLC that has spread to other parts of the body and is caused by a defect in either a gene called ALK (anaplastic lymphoma kinase) or a gene called ROS1.
• children 1 year of age and older and young adults with ALCL or children 1 year of age and older and adults with IMT when your ALCL or IMT with a defect in a gene called ALK has returned, or you have tried a treatment and it did not work or is no longer working, or specifically for IMT, when the tumor cannot be surgically removed.

It is not known if crizotinib is safe and effective in older adults with ALCL or in children younger than 1 year of age with ALCL or IMT.

Crizotinib may cause serious side effects, including:

• Liver problems. Crizotinib may cause life-threatening liver injury that may lead to death. Your healthcare provider should do blood tests to check your liver every 2 weeks during the first 2 months of treatment with this medication, then once a month and as recommended by your healthcare provider during treatment. Tell your healthcare provider right away if you develop any of the following new or worsening symptoms:
  • yellowing of your skin or the white part of your eyes
  • severe tiredness
  • dark or brown (tea color) urine
  • nausea or vomiting
  • decreased appetite
  • pain on the right side of your stomach
  • bleed or bruise more easily than normal
  • itching
• Lung problems (pneumonitis). Crizotinib may cause life-threatening lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you have any new or worsening symptoms, including:
  • trouble breathing or shortness of breath
  • cough with or without mucous
  • fever
• Heart problems. Crizotinib may cause very slow, very fast, or abnormal heartbeats. Your healthcare provider may check your pulse rate and blood pressure regularly during treatment with this medication. Tell your healthcare provider right away if you feel dizzy or faint or have abnormal heartbeats. Tell your healthcare provider if you take any heart or blood pressure medicines.
• Severe vision problems. Vision problems are common with crizotinib. These problems usually happen within 1 week of starting treatment. Vision problems with this medication can be severe and may cause partial or complete loss of vision in one or both eyes. Your healthcare provider may hold or permanently stop your treatment and refer you to an eye specialist if any vision problems develop during treatment. Tell your healthcare provider right away if you have any new vision problems, loss of vision or any change in vision, including:
  • double vision
  • seeing flashes of light
  • blurry vision
  • light hurting your eyes
  • new or increased floaters
    
    In addition, for children or young adults taking crizotinib to treat ALCL or children taking it to treat IMT: Your healthcare provider may refer you to an eye specialist before starting this medication, and within 1 month of starting it to check for vision problems. You should have an eye examination every 3 months during treatment with this medication and more often if there are any new vision problems.
• Severe stomach, intestine, and mouth (gastrointestinal) problems in children or young adults with ALCL or children with IMT. Crizotinib may cause severe diarrhea, nausea, vomiting, or mouth sores. Tell your healthcare provider right away if problems with swallowing, vomiting, or diarrhea develop during treatment.
  • Your healthcare provider may give medicines as needed to prevent or treat diarrhea, nausea, and vomiting.
  • Your healthcare provider may recommend drinking more fluids or may prescribe electrolyte supplements or other kinds of nutritional support if severe symptoms develop.

See "What are the side effects of crizotinib?" below for more information about side effects.

• Crizotinib should be taken exactly as prescribed by your healthcare provider.
• Capsules should be swallowed whole.
• May be taken with or without food.
• Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with this medication if you have certain side effects. Do not change the dose or stop treatment with this medication unless your healthcare provider tells you to.
• If you vomit after taking a dose, do not take an extra dose. The next dose should be taken at the regular time.
• This medication should be given to children under adult supervision.

• In patients with metastatic (cancer that has spread) NSCLC the recommended dosage of crizotinib is 250 mg orally twice daily.
• In patients with systemic ALCL the recommended dosage of crizotinib is 280 mg/m² orally twice daily based on body surface area.
• In patients with unresectable IMT the recommended adult dosage of crizotinib is 250 mg orally twice daily and the recommended pediatric dosage is 280 mg/m² orally twice daily based on body surface area.
• See full prescribing information for dosage adjustments by indication for patients with moderate or severe hepatic impairment or severe renal impairment.

Before taking crizotinib, tell your healthcare provider about all of your medical conditions, including if you:

• have liver or kidney problems
• have lung problems
• have heart problems, including a condition called long QT syndrome
• have vision or eye problems

If a dose of crizotinib is missed, it should be taken as soon as you remember. If it is close to the time of the next dose (within 6 hours), the missed dose should be skipped, and the next dose should be taken at the regular time.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

Do not eat grapefruit or drink grapefruit juice while taking this medication.

• Do not drink grapefruit juice, eat grapefruit or take supplements containing grapefruit extract during treatment with crizotinib. These may increase the amount of this medication in the blood.
• Crizotinib can cause changes in vision, dizziness, and tiredness. Do not drive or operate machinery if you have any of these symptoms.
• Avoid spending prolonged time in sunlight. Crizotinib can make your skin sensitive to the sun (photosensitivity), and you may burn more easily. You should use sunscreen and wear protective clothing that covers your skin to help protect against sunburn if you have to be in the sunlight during treatment with this medication.

Crizotinib may cause serious side effects, including:

• See "Important information" above.

The most common side effects of crizotinib in people with NSCLC include:

• vision problems
• nausea, diarrhea, or vomiting
• swelling of your hands, feet, face, and eyes
• constipation
• increased liver function blood tests
• tiredness
• decreased appetite
• upper respiratory infection
• dizziness
• feeling of numbness or tingling in your arms or legs

The most common side effects of crizotinib in people with ALCL include:

• diarrhea, vomiting, or nausea
• vision problems
• headache
• muscle and joint pain
• mouth sores
• tiredness
• decreased appetite
• fever
• stomach-area (abdominal) pain
• cough
• itchy skin
• low blood counts

The most common side effects of crizotinib in adults with IMT include:

• vision problems
• nausea
• swelling of your hands, feet, face, or eyes

The most common side effects of crizotinib in children with IMT include:

• diarrhea, vomiting, or nausea
• stomach-area (abdominal) pain
• rash
• vision problems
• upper respiratory infection
• cough
• fever
• muscle and joint pain
• tiredness
• swelling of your hands, feet, face, or eyes
• constipation
• headache

Crizotinib may cause fertility problems in females and males, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility.

These are not all of the possible side effects of this medication. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your healthcare provider about the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.

Keep all appointments with your doctor and the laboratory. Your doctor will order a lab test before you begin your treatment to see whether your cancer can be treated with crizotinib and will also order certain lab tests during your treatment to check your body's response to crizotinib. Your doctor will also check your heart rate and blood pressure regularly during your treatment.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.