Entrectinib

Generic name: entrectinib
Brand name: Rozlytrek
Dosage form: oral capsule (100 mg; 200 mg)
Drug class: Multikinase inhibitors

Medically reviewed by  A Ras MD.

What is entrectinib?

Entrectinib is a prescription medicine that is used to treat cancer.

Description

Entrectinib is a kinase inhibitor. The molecular formula for entrectinib is C31H34F2N6O2 and the molecular weight is 560.64 Daltons. The chemical name is N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methylpiperazin-1-yl)-2-(tetrahydro-2H-pyran-4-ylamino) benzamide. The chemical structure of entrectinib is as follows:

Entrectinib is white to pale pink powder.

ROZLYTREK (entrectinib) capsules for oral use are supplied as printed hard-shell capsules containing 100 mg (yellow opaque HPMC capsule) or 200 mg of entrectinib (orange opaque HPMC capsule). Inactive ingredients are tartaric acid, lactose anhydrous, hypromellose, crospovidone, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate.

The yellow opaque capsule shell contains hypromellose, titanium dioxide, and yellow iron oxide. The orange opaque capsule shell contains hypromellose, titanium dioxide, and FD&C yellow #6. The printing ink contains shellac, propylene glycol, strong ammonia solution, and FD&C blue #2 aluminum lake.

Mechanism of Action

Entrectinib is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK) with IC50 values of 0.1 to 2 nM. Entrectinib also inhibits JAK2 and TNK2 with IC50 values > 5 nM. The major active metabolite of entrectinib, M5, showed similar in vitro activity against TRK, ROS1, and ALK.

Fusion proteins that include TRK, ROS1, or ALK kinase domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Entrectinib demonstrated in vitro and in vivo inhibition of cancer cell lines derived from multiple tumor types harboring NTRK, ROS1, and ALK fusion genes.

Entrectinib demonstrated steady-state brain-to-plasma concentration ratios of 0.4 – 2.2 in multiple animal species (mice, rats, and dogs) and demonstrated in vivo anti-tumor activity in mice with intracranial implantation of TRKA- and ALK-driven tumor cell lines.

Before taking entrectinib, tell your doctor:

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

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

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 entrectinib 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 entrectinib?

• Tell all of your health care providers that you take entrectinib. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how entrectinib affects you.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You will need to have your heart checked before starting entrectinib and while taking it. This includes an ECG. Talk with your doctor.
• Avoid grapefruit and grapefruit juice.
• High uric acid levels have happened with entrectinib. Call your doctor right away if you have joint pain, swelling, or stiffness.
• This medicine may cause or make heart failure worse. Talk with the doctor.
• A type of abnormal heartbeat (prolonged QT interval) can happen with entrectinib. 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 raise the chance of a broken bone. Talk with the doctor.
• Use with care in children. Talk with the doctor.
• This medicine may cause harm to an unborn baby. A pregnancy test will be done before you start entrectinib to show that you are NOT pregnant.
• Women must use birth control while taking entrectinib and for some time after the last dose. Ask your doctor how long to use birth control. If you get pregnant, call your doctor right away.
• Men with a partner who may get pregnant must use birth control while taking entrectinib and for some time after the last dose. Ask your doctor how long to use birth control. If your partner gets pregnant, call the doctor right away.

How is entrectinib best taken?

Use entrectinib 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, open, or dissolve.
• Keep taking entrectinib as you have been told by your doctor or other health care provider, even if you feel well.
• If you throw up right after taking entrectinib, take 1 more dose as soon as you can on the same day. Then go back to your normal time the next day.

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 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 entrectinib 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 nervous system problems like a burning, numbness, or tingling feeling; change in balance; confusion; dizziness; hallucinations (seeing or hearing things that are not there); memory problems or loss; new or worse behavior or mood changes like anxiety, depression, or thoughts of killing yourself; trouble focusing; trouble sleeping; or trouble thinking or speaking.
• 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 fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
• Shortness of breath, a big weight gain, or swelling in the arms or legs.
• Bone pain.
• Change in eyesight.
• If bright lights bother your eyes.
• Swelling.
• Very bad dizziness or passing out.
• Feeling very tired or weak.
• Fever, chills, or sore throat.

What are some other side effects of entrectinib?

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:

• Feeling dizzy, tired, or weak.
• Constipation, diarrhea, stomach pain, upset stomach, throwing up, or feeling less hungry.
• Change in taste.
• Muscle pain or weakness.
• Back pain.
• Pain in arms or legs.
• Weight gain.
• 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 entrectinib?

• 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.