Larotrectinib is used to treat certain tumors that are caused by an abnormal "NTRK" gene. Larotrectinib is used when the cancer has spread to other parts of the body or cannot be removed with surgery or other cancer treatments.

Larotrectinib is sometimes given after other cancer treatments did not work or have stopped working.

Larotrectinib was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, some people responded to larotrectinib, but further studies are needed.

Larotrectinib may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Your doctor will perform a test to make sure larotrectinib is the right treatment for your type of tumor.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Take this medicine with a full glass of water.

You may take larotrectinib with or without food.

Swallow the capsule whole and do not crush, chew, break, or open it.

Measure liquid medicine carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).

Read and carefully follow any Instructions for Use provided with your medicine. Ask your doctor or pharmacist if you do not understand these instructions.

You will need frequent medical tests to check your liver function.

Your doctor will determine how long to treat you with larotrectinib.

If you vomit shortly after taking larotrectinib, do not take another dose. Wait until your next scheduled dose time to take the medicine again.

Store the capsules at room temperature, away from moisture and heat.

Store the liquid medicine in the refrigerator, do not freeze. Throw away any unused liquid after 90 days.

Usual Adult Dose for Solid Tumors:

Body surface area least 1 m2:
100 mg orally 2 times a day until disease progression or unacceptable toxicity

Comments:
-Select patients for treatment with this drug based on the presence of a NTRK gene fusion in tumor specimens.

Use: For the treatment of adult patients with solid tumors that:
-Have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation
-Are metastatic or where surgical resection is likely to result in severe morbidity
-Have no satisfactory alternative treatments or that have progressed following treatment

Usual Pediatric Dose for Solid Tumors:

28 days and older:
-Body surface area at least 1 m2: 100 mg orally 2 times a day until disease progression or unacceptable toxicity
-Body surface area less than 1 m2: 100 mg/m2 orally 2 times a day until disease progression or unacceptable toxicity.

Comments:
-Select patients for treatment with this drug based on the presence of a NTRK gene fusion in tumor specimens.

Use: For the treatment of pediatric patients with solid tumors that:
-Have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation
-Are metastatic or where surgical resection is likely to result in severe morbidity
-Have no satisfactory alternative treatments or that have progressed following treatment

Tell your doctor if you have ever had:

• liver disease; or

• nerve problems.

You may need to have a negative pregnancy test before starting this treatment.

Both men and women using larotrectinib should use effective birth control to prevent pregnancy. Larotrectinib can harm an unborn baby or cause birth defects if the mother or father is using this medicine. Keep using birth control for at least 1 week after your last dose.

This medicine may affect fertility (ability to have children) in women. However, it is important to use birth control to prevent pregnancy because larotrectinib can harm an unborn baby.

Do not breast-feed while using this medicine, and for at least 1 week after your last dose.

Use the medicine as soon as you can, but skip the missed dose if your next dose is due in less than 6 hours. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store the capsules at room temperature and away from excess heat and moisture (not in the bathroom). Keep the oral solution in the refrigerator and closed tightly; do not freeze. Dispose of any unused oral solution 90 days after opening the bottle for the first time.

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

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

Avoid driving or hazardous activity until you know how larotrectinib will affect you. Your reactions could be impaired.

Grapefruit may interact with larotrectinib and lead to unwanted side effects. Avoid the use of grapefruit products.

Avoid taking an herbal supplement containing St. John's wort.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Larotrectinib may cause serious side effects. Call your doctor at once if you have:

• severe or ongoing stomach pain, vomiting, or diarrhea;

• confusion, memory problems, severe dizziness;

• problems with speech or coordination;

• numbness, tingling, or burning pain in your hands or feet;

• fever, flu symptoms, sore throat, cough;

• sores or ulcers in your mouth or on your skin;

• unusual tiredness, feeling light-headed or short of breath;

• pale skin, cold hands and feet;

• pain, warmth, redness, or swelling under your skin; or

• liver problems--loss of appetite, stomach pain (upper right side), nausea, vomiting, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects of larotrectinib may include:

• nausea, vomiting, diarrhea, constipation;

• cough;

• dizziness;

• tiredness; or

• abnormal liver function tests.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Other drugs may affect larotrectinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests before and during treatment to check your body's response to larotrectinib. Your doctor will order a lab test before you begin your treatment to see whether your cancer can be treated with larotrectinib.

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.