Brigatinib

Generic name: brigatinib
Brand name: Alunbrig
Dosage form: oral tablet (180 mg; 30 mg; 90 mg; 90 mg-180 mg)
Drug class: Multikinase inhibitors

Medically reviewed by  A Ras MD.

What is brigatinib?

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

Description

Brigatinib is a kinase inhibitor. The chemical name for brigatinib is 5-chloro-N4-[2-(dimethylphosphoryl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine. The molecular formula is C29H39ClN7O2P which corresponds to a formula weight of 584.10 g/mol. Brigatinib has no chiral centers. The chemical structure is shown below:

Chemical Structure

Brigatinib is an off-white to beige/tan solid. The pKas were determined to be: 1.73 ± 0.02 (base), 3.65 ± 0.01 (base), 4.72 ± 0.01 (base), and 8.04 ± 0.01 (base).

ALUNBRIG is supplied for oral use as film-coated tablets containing 180 mg, 90 mg or 30 mg of brigatinib and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate (Type A), magnesium stearate, and hydrophobic colloidal silica. The tablet coating consists of talc, polyethylene glycol, polyvinyl alcohol, and titanium dioxide.

Mechanism of Action

Brigatinib is a tyrosine kinase inhibitor (TKI) with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also 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.

At clinically achievable concentrations (≤500 nM), brigatinib inhibited the in vitro viability of cells expressing EML4-ALK and 17 mutant forms associated with resistance to ALK inhibitors including crizotinib, as well as EGFR-Del (E746-A750), ROS1-L2026M, FLT3-F691L, and FLT3-D835Y. Brigatinib exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib. Brigatinib also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell line.

 

Before taking brigatinib, tell your doctor:

  • If you are allergic to brigatinib; 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 high blood pressure.
  • If you take any other drugs (prescription or OTC, natural products, vitamins). There are many drugs that interact with brigatinib, like certain drugs that are used for HIV, infections, or seizures.
  • If you are breast-feeding. Do not breast-feed while you take brigatinib and for 1 week after your last dose.

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

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 brigatinib 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 brigatinib?

  • Tell all of your health care providers that you take brigatinib. This includes your doctors, nurses, pharmacists, and dentists.
  • This medicine may cause high blood pressure.
  • Check blood pressure and heart rate as the doctor has told you.
  • Have blood work checked as you have been told by the doctor. Talk with the doctor.
  • High blood sugar has happened with brigatinib. This includes diabetes that is new or worse.
  • Check your blood sugar as you have been told by your doctor.
  • Avoid grapefruit and grapefruit juice.
  • This medicine may affect being able to father a child. Talk with the doctor.
  • 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 and your sex partner gets pregnant while you take brigatinib 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.
  • If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting brigatinib. Talk with your doctor.
  • Use a non-hormone type of birth control like condoms to prevent pregnancy while taking brigatinib and for 4 months after your last dose. Birth control pills and other hormone-based birth control may not work as well to prevent pregnancy.
  • If you get pregnant while taking brigatinib or within 4 months after your last dose, call your doctor right away.

How is brigatinib best taken?

Use brigatinib 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, break, or crush.
  • Keep taking brigatinib 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?

  • 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 brigatinib 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 pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • 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 a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
  • 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.
  • Slow heartbeat.
  • Chest pain.
  • Change in eyesight.
  • Seeing double.
  • If bright lights bother your eyes.
  • Muscle pain or weakness.
  • Muscle spasm.
  • Fever.
  • A burning, numbness, or tingling feeling that is not normal.
  • Feeling very tired or weak.
  • Some people have had lung problems with brigatinib. 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 brigatinib?

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:

  • Upset stomach or throwing up.
  • Diarrhea.
  • Constipation.
  • Belly pain.
  • Not hungry.
  • Feeling tired or weak.
  • Headache.
  • Back pain.
  • Joint pain.
  • Pain in arms or legs.
  • Trouble sleeping.

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 brigatinib?

  • 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 .