Crizotinib

Generic name: crizotinib
Brand name: Xalkori
Dosage form: oral capsule
Drug class: Multikinase inhibitors

Medically reviewed by  A Ras MD.

What is crizotinib?

Crizotinib is a prescription medicine that is used to treat lung cancer.

Description

Crizotinib is a kinase inhibitor. The molecular formula for crizotinib is C21H22Cl2FN5O and the molecular weight is 450.34 daltons. Crizotinib is described chemically as (R)-3-[1-(2,6-Dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]pyridin-2-amine.

The chemical structure of crizotinib is shown below:

Crizotinib is a white to pale-yellow powder with a pKa of 9.4 (piperidinium cation) and 5.6 (pyridinium cation). The solubility of crizotinib in aqueous media decreases over the range pH 1.6 to pH 8.2 from greater than 10 mg/mL to less than 0.1 mg/mL. The log of the distribution coefficient (octanol/water) at pH 7.4 is 1.65.

XALKORI (crizotinib) for oral administration is supplied as printed hard-shell capsules containing 250 mg or 200 mg of crizotinib together with colloidal silicon dioxide, microcrystalline cellulose, anhydrous dibasic calcium phosphate, sodium starch glycolate, magnesium stearate, and hard gelatin capsule shells as inactive ingredients.

The pink opaque capsule shell components contain gelatin, titanium dioxide, and red iron oxide. The white opaque capsule shell components contain gelatin and titanium dioxide. The printing ink contains shellac, propylene glycol, strong ammonia solution, potassium hydroxide, and black iron oxide.

Mechanism of Action

Crizotinib is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), ROS1 (c-ros), and Recepteur d’Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene’s expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. Crizotinib demonstrated concentration-dependent inhibition of ALK, ROS1, and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed echinoderm microtubule-associated protein-like 4 (EML4)- or nucleophosmin (NPM)-ALK fusion proteins or c-Met.

In vitro, crizotinib induced apoptosis and inhibited proliferation and ALK-mediated signaling in ALCL-derived cell lines (containing NPM-ALK) at clinically achievable exposures. In vivo data obtained in an ALCL-derived mouse model showed complete regression of the tumor at a dose of 100 mg/kg once daily.

Before taking crizotinib, tell your doctor:

• If you are allergic to crizotinib; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you have a long QT on ECG.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with crizotinib, like certain drugs that are used for HIV, infections, or seizures. There are many drugs that must not be taken with crizotinib.
• If you are taking any drugs that can cause a slow heartbeat. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
• If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
• If you are taking St. John’s wort. Do not take St. John’s wort with crizotinib. This medicine may not work as well.
• If you are breast-feeding. Do not breast-feed while you take crizotinib or within 45 days after your last dose.

This is not a list of all drugs or health problems that interact with crizotinib.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take crizotinib with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take crizotinib?

• Tell all of your health care providers that you take crizotinib. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert or have clear eyesight until you see how crizotinib affects you.
• Constipation, diarrhea, throwing up, and upset stomach are common with crizotinib. If these happen, talk with your doctor about ways to lower these side effects. Call your doctor right away if any of these effects bother you, do not go away, or get very bad.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Check blood pressure and heart rate as the doctor has told you.
• Avoid grapefruit and grapefruit juice.
• A type of abnormal heartbeat (prolonged QT interval) can happen with crizotinib. Call your doctor right away if you have a fast heartbeat, a heartbeat that does not feel normal, or if you pass out.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child.
• If you are a man and have sex with a female who could get pregnant, protect her from pregnancy during treatment and for 3 months after your last dose.
• If you are a man with a sex partner who is pregnant or plans on getting pregnant at any time while you are being treated or within 3 months after your last dose, talk with your doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting crizotinib. Talk with your doctor.
• Use birth control that you can trust to prevent pregnancy while taking crizotinib and for 45 days after your last dose.
• If you get pregnant while taking crizotinib or within 45 days after your last dose, call your doctor right away.

How is crizotinib best taken?

Use crizotinib as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Swallow whole. Do not chew, open, or crush.
• Keep taking crizotinib as you have been told by your doctor or other health care provider, even if you feel well.
• If you throw up after taking a dose, do not repeat the dose. Take your next dose at your normal time.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is less than 6 hours until the next dose, skip the missed dose and go back to the normal time.
• Do not take 2 doses at the same time or extra doses.

What are the side effects of crizotinib that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Dizziness.
• Slow heartbeat.
• Coughing up blood.
• Chest pain or pressure.
• A burning, numbness, or tingling feeling that is not normal.
• Trouble walking.
• Trouble swallowing.
• Swelling.
• Low white blood cell counts have happened with crizotinib. This may lead to a higher chance of getting an infection. Call your doctor right away if you have signs of infection like fever, chills, or sore throat.
• Very bad and sometimes deadly liver problems have happened with crizotinib. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Some people have had lung problems with crizotinib. Sometimes, this has been deadly. Call your doctor right away if you have signs of lung problems like shortness of breath or other trouble breathing, cough that is new or worse, or fever.
• Very bad eyesight problems like loss of eyesight have happened with crizotinib. Most of the time, these happen during the first week of taking crizotinib. Call your doctor right away if you have blurred eyesight, bright lights bother your eyes, you see flashes of light or floaters, have loss of eyesight, or trouble seeing out of one or both eyes.

What are some other side effects of crizotinib?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Not hungry.
• Feeling tired or weak.
• Change in taste.
• Stomach pain or heartburn.
• Signs of a common cold.
• Weight gain or loss.
• Pain in arms or legs.
• Muscle spasm.
• Headache.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out crizotinib?

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

PRINCIPAL DISPLAY PANEL – 250 MG CAPSULE BOTTLE LABEL

• ALWAYS DISPENSE ENCLOSED MEDICATION
  GUIDE TO EACH PATIENT
• Pfizer
  NDC 0069-8140-20
• XALKORI®
  (crizotinib) capsules
  250 mg
• Swallow capsule whole
• 60 Capsules
  Rx only

PRINCIPAL DISPLAY PANEL – 200 MG CAPSULE BOTTLE LABEL

• ALWAYS DISPENSE ENCLOSED MEDICATION
  GUIDE TO EACH PATIENT
• Pfizer
  NDC 0069-8141-20
• XALKORI®
  (crizotinib) capsules
  200 mg
• Swallow capsule whole
• 60 Capsules
  Rx only

SRC: NLM .