Drug information of Larotrectinib


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.

Mechanism of effect

Larotrectinib is a potent and highly selective small-molecule inhibitor of the 3 tropomyosin receptor kinase (TRK) proteins, TRKA, TRKB, and TRKC (Drilon 2018). TRKA, TRKB, and TRKC are encoded by neurotrophic receptor tyrosine kinase (NTRK) genes, NTRK1, NTRK2, and NTRK3. Chromosomal rearrangements involving fusions of NTRK genes may result in constitutively-activated chimeric TRK fusion proteins, acting as an oncogenic driver to promote cell proliferation and survival in tumor cell lines. Larotrectinib has anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression.


48 L
Hepatic; primarily via CYP3A4; forms an O-linked glucuronide metabolite
Feces (58%; 5% unchanged); Urine (39%; 20% unchanged)
Time to Peak:
~1 hour
Half-Life Elimination:
2.9 hours
Protein Binding:
70%; to plasma proteins

Drug indications

Solid tumors: Treatment of solid tumors (in adult and pediatric patients) 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; and have no satisfactory alternative treatments or that have progressed following treatment.


- 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

-Take this drug with or without food.
-Select patients for treatment with this drug based on the presence of a NTRK gene fusion in tumor specimens. An FDA-approved test for the detection of NTRK
gene fusion is not currently available.

- 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.

-Take this drug with or without food.
-Select patients for treatment with this drug based on the presence of a NTRK gene fusion in tumor specimens. An FDA-approved test for the detection of NTRK
gene fusion is not currently available.

Drug contraindications

There are no contraindications listed in the manufacturer's labeling.

Side effects

Along with its needed effects, larotrectinib may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking larotrectinib:
More common
- Black, tarry, stools
- bloating or swelling of the face, arms, hands, lower - legs, or feet
- blurred vision
- chills
- cough
- dizziness
- falls
- fever
- headache
- lower back or side pain
- nervousness
- painful or difficult urination
- pale skin
- pounding in the ears
- rapid weight gain
- slow or fast heartbeat
- sore throat
- tightness in the chest
- tingling of the hands or feet
- troubled breathing
- troubled breathing with exertion
- ulcers, sores, or white spots in the mouth
- unusual bleeding or bruising
- unusual tiredness or weakness
- unusual weight gain or loss
Less common:
- Chest pain or discomfort
- chills
- confusion
- decreased urination
- diarrhea
- dry mouth
- fainting
- heartburn
- increase in heart rate
- increased thirst
- indigestion
- irregular heartbeat
- itching, pain, redness, swelling, tenderness, or warmth on the skin
- loss of consciousness
- muscle pain, cramps, or weakness
- nausea
- problems with movement, walking, or speech
- rapid, shallow breathing
- seizures
- severe abdominal pain, cramping, or burning
- stomach pain
- sunken eyes
- swelling of the face, ankles, or hands
- vomiting
- vomiting of material that looks like coffee grounds, severe and continuing
- wrinkled skin
- yellow skin or eyes
Some side effects of larotrectinib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common :
- Back pain
- constipation
- decreased appetite
- difficulty in moving
- increased weight
- joint pain or swelling
- muscle stiffness
- pain in the arms or legs
- stuffy nose
Less common :
 - Lack or loss of strength


Concerns related to adverse effects:
• Bone marrow suppression: Anemia and neutropenia have been observed (usually grades 1 or 2).
• Gastrointestinal toxicity: Nausea, vomiting, constipation, and diarrhea may occur (usually mild).
• Hepatotoxicity: Transaminase increase (of any grade) commonly occurred with larotrectinib; grade 3 AST or ALT elevations were reported; grade 4 ALT elevations occurred rarely. The median time to onset of AST and ALT elevation was 2 months (range: 1 month to 2.6 years for AST elevation and 1 month to 1.1 years for ALT elevation). AST and ALT elevations leading to dose modifications and/or permanent discontinuation have occurred. Monitor liver functions tests (including ALT and AST) every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. May require treatment interruption, dosage reduction, and/or permanent discontinuation (based on the severity). Reduced initial doses are recommended in patients with preexisting moderate to severe hepatic impairment.
• Neurotoxicity: Neurologic adverse reactions (of any grade) commonly occurred with larotrectinib, including grade 3 and 4 neurotoxicity. Most neurologic adverse reactions occurred within the first 3 months of treatment (range: 1 day to 2.2 years). Grade 3 neurologic adverse reactions included delirium, dysarthria, dizziness, gait disturbance, and paresthesia; grade 4 encephalopathy was reported (rare). Neurologic adverse reactions leading to dose modification included dizziness, gait disturbance, delirium, memory impairment, and tremor. Advise patients and caregivers of the potential for neurotoxicity. Patients experiencing neurotoxicity should not perform tasks requiring mental alertness (eg, driving or operating heavy machinery) if they are experiencing neurologic adverse reactions. May require treatment interruption, dosage reduction, and/or permanent discontinuation (based on the severity).

Points of recommendation

Before taking this medicine
- 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.
- 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.
Capsules: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F).
Solution: Store at 2°C to 8°C (36°F to 46°F). Do not freeze. Discard unused portion of oral solution 90 days after initial opening of the bottle.

Pregnancy level


Use is not recommended.
US FDA pregnancy category: Not assigned.

Breast feeding warning

Use is not recommended.

Excreted into human milk: Unknown
Excreted into animal milk: Data not available

-The effects in the nursing infant are unknown.
-Advise women not to breastfeed during therapy and for 1 week after.

Drug forms


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