Ceritinib

Generic name: ceritinib
Brand name: Zykadia
Dosage forms: oral capsule (150 mg); oral tablet (150 mg)
Drug class: Multikinase inhibitors

Medically reviewed by  A Ras MD.

What is ceritinib?

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

Description

Ceritinib is a kinase inhibitor for oral administration. The molecular formula for ceritinib is C28H36N5O3ClS. The molecular weight is 558.14 g/mol. Ceritinib is described chemically as 5-Chloro-N4-[2-[(1-methylethyl)sulfonyl]phenyl]-N2-[5-methyl-2-(1-methylethoxy)-4-(4-piperidinyl)phenyl]-2,4-pyrimidinediamine.

The chemical structure of ceritinib is shown below:

The chemical structure of ceritinib.

Ceritinib is a white to almost white or light yellow powder.

ZYKADIA is supplied as printed hard-gelatin capsules containing 150 mg of ceritinib and the following inactive ingredients: colloidal silicon dioxide, hard gelatin capsule shells, low substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The capsule shell is composed of FD&C Blue # 2, gelatin, and titanium dioxide.

ZYKADIA is supplied as film-coated tablets containing 150 mg of ceritinib and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, low-substituted hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose and povidone. The tablet coating contains FD&C Blue # 2 aluminum lake, hypromellose, polyethylene glycol 4000, talc, and titanium dioxide.

Mechanism of Action

Ceritinib is a kinase inhibitor. Targets of ceritinib inhibition identified in either biochemical or cellular assays at clinically relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells in in vitro and in vivo assays.

Ceritinib inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice and rats. Ceritinib exhibited dose-dependent anti-tumor activity in mice bearing EML4-ALK-positive NSCLC xenografts with demonstrated resistance to crizotinib, at concentrations within a clinically relevant range.

Before taking ceritinib, tell your doctor:

  • If you are allergic to ceritinib; 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 other drugs (prescription or OTC, natural products, vitamins). There are many drugs that interact with ceritinib, like certain drugs that are used for HIV, infections, or seizures.
  • 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 St. John’s wort. Do not take St. John’s wort with ceritinib. This medicine may not work as well.
  • If you are breast-feeding. Do not breast-feed while you take ceritinib and for 2 weeks after your last dose.

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

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 ceritinib 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 ceritinib?

  • Tell all of your health care providers that you take ceritinib. This includes your doctors, nurses, pharmacists, and dentists.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • An unsafe heartbeat that is not normal (long QT on ECG) has happened with ceritinib. This may raise the chance of sudden death. Talk with the doctor.
  • Check blood pressure and heart rate as the doctor has told you.
  • Diarrhea, throwing up, upset stomach, and feeling less hungry are common with ceritinib. 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 get better, or get very bad.
  • If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
  • Check your blood sugar as you have been told by your doctor.
  • Avoid grapefruit and grapefruit juice.
  • 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. Use a condom.
  • If you are a man and your sex partner gets pregnant while you take ceritinib or within 3 months after your last dose, call your doctor right away.
  • This medicine may cause harm to the unborn baby if you take it while you are pregnant.
  • Use birth control that you can trust to prevent pregnancy while taking ceritinib and for 6 months after stopping ceritinib.
  • If you get pregnant while taking ceritinib or within 6 months after your last dose, call your doctor right away.

How is ceritinib best taken?

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

  • Take ceritinib with food.
  • Keep taking ceritinib 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, with food.
  • If it is less than 12 hours until the next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

What are the side effects of ceritinib 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 high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
  • 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.
  • Signs of low phosphate levels like change in eyesight, feeling confused, mood changes, muscle pain or weakness, shortness of breath or other breathing problems, or trouble swallowing.
  • Any unexplained bruising or bleeding.
  • Fast or slow heartbeat.
  • A heartbeat that does not feel normal.
  • Chest pain or pressure or passing out.
  • Dizziness.
  • A burning, numbness, or tingling feeling that is not normal.
  • Change in balance.
  • Muscle weakness.
  • Change in eyesight.
  • Fever or chills.
  • Feeling very tired or weak.
  • Very bad and sometimes deadly pancreas problems (pancreatitis) have happened with ceritinib. Call your doctor right away if you have very bad stomach pain, very bad back pain, or very upset stomach or throwing up.
  • Some people have had lung problems with ceritinib. 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.

What are some other side effects of ceritinib?

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:

  • Stomach pain or heartburn.
  • Constipation.
  • Weight loss.
  • Feeling tired or weak.
  • Back pain.
  • Pain in arms or legs.
  • Muscle pain.
  • Cough.
  • 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 ceritinib?

  • 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.

 

SRC: NLM .