Entrectinib

Entrectinib is used to treat a certain type of non-small cell lung cancer (NSCLC) in adults that has spread to other parts of the body. It is also used to treat certain types of solid tumors in adults and children age 1 month and older that cannot be treated by surgery or that has spread to other parts of the body and that worsened after treatment with other chemotherapy medications. Entrectinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

Entrectinib comes as a capsule, capsules prepared as a suspension, or oral pellets to take by mouth. It is usually taken with or without food once daily. Capsules can either be swallowed whole or given as a prepared oral suspension for patients who are unable to swallow capsules or need to have the medicine given via gastric or nasogastric tube. If taking the capsules as an oral suspension, open the correct number of capsules and pour the contents into room temperature drinking water or milk per prescriber instructions. Let the suspension sit for 15 minutes before taking it and then follow the prescribed amount with water. If you cannot take the suspension right away, it can be stored at room temperature for up to 2 hours. If more than 2 hours have passed, throw it away. Pellets can be placed on one or more spoonfuls of soft food (e.g. applesauce, pudding, yogurt) and taken within 20 minutes of placing it on food and followed with water..Make sure you use the whole packet of pellets and do not use them to make a suspension or give them through a gastric or nasogastric tube. Take entrectinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take entrectinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Do not chew or crush capsule contents or pellets.

If you vomit immediately after you take entrectinib, take another dose as soon as possible.

Your doctor may temporarily or permanently stop your treatment or decrease the dose if you experience serious side effects of entrectinib. Talk to your doctor about how you are feeling during your treatment.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking entrectinib,

• tell your doctor and pharmacist if you are allergic to entrectinib, any other medications, or any of the ingredients in entrectinib capsules. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• The following nonprescription or herbal products may interact with entrectinib: St. John's Wort. Be sure to let your doctor and pharmacist know that you are taking these medications before you start taking entrectinib. Do not start any of these medications while taking entrectinib without discussing with your healthcare provider.
• tell your doctor if you have or have ever had a nervous system condition; eye or vision problems; a prolonged QT interval (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death), a slow or irregular heartbeat, a heart attack, heart failure, or any other heart problems; or kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or if you plan on fathering a child. If you are female, you will need to take a pregnancy test before you start treatment and use birth control to prevent pregnancy during your treatment and for at least 5 weeks after your final dose. If you are a male, you and your partner should use birth control during your treatment with entrectinib and for 3 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you or your partner become pregnant while taking entrectinib, call your doctor immediately. Entrectinib may harm the fetus.
• tell your doctor if you are breastfeeding. You should not breastfeed while you are taking entrectinib and for 7 days after the final dose.
• you should know that entrectinib may make cause dizziness or confusion. Do not drive a car or operate machinery until you know how this medication affects you.

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

If you miss a dose by less than 12 hours, take the missed dose as soon as you remember it and then take the next dose at the scheduled time. However, if you miss a dose by more than 12 hours, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Entrectinib may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• tiredness
• constipation
• diarrhea
• nausea
• vomiting
• abdominal (stomach area) pain
• taste changes
• numbness, pain, burning, or tingling in the arms, hands, feet, or legs
• headache
• joint pain
• muscle pain or weakness
• leg, arm, or back pain
• increased weight
• rash
• difficulty falling or staying asleep

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

• difficulty with learning, memory, attention, or problem solving
• mood changes such as anxiety, depression, confusion, or agitation
• feeling unsteady or having trouble keeping your balance, sleepiness, or dizziness
• hallucinations (seeing things or hearing voices that do not exist)
• trouble speaking or understanding
• bone pain, difficulty moving, or bone abnormalities
• double vision, blurred vision, eye sensitivity to light, loss of vision, or other changes in vision
• red, swollen, stiff, or painful joints
• pain in upper right part of the stomach, yellowing of skin or eyes, nausea or vomiting, loss of appetite, or bleeding or bruising easily
• shortness of breath; sudden weight gain; persistent coughing or wheezing; tiredness, weakness, or fatigue; difficulty breathing when lying down; or swelling of the arms, legs, hands, or feet
• feeling faint, lightheaded, or dizzy
• fast or irregular heartbeat
• cough, fever, chills, or other signs of infection
• difficult, painful, or bloody urination
• intense low back or side pain

Entrectinib may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Entrectinib may increase the risk of fractures. Talk to your doctor about the risks of taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

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. https://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 (https://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

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 entrectinib. Your doctor may order certain lab tests before and during your treatment to check your body's response to entrectinib.

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.

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