Larotrectinib

Pronunciation: pronunciation varies by local usage.

Generic name: larotrectinib
Brand names: VITRAKVI
Drug class: Kinase inhibitor (tropomyosin receptor kinase, TRK, inhibitor)
Form: Capsules and oral solution
Route: Oral
Legal status: Prescription-only medicine

Availability and supply rules vary by country

Trade names by country: United States

What larotrectinib is and how it works

Larotrectinib is a kinase inhibitor that targets tropomyosin receptor kinase (TRK) proteins. It is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity, and that have no satisfactory alternative treatments or have progressed following treatment. This indication is approved under accelerated approval based on overall response rate and duration of response. (1)

Patients are selected for therapy based on an FDA-approved test for NTRK gene fusion. Larotrectinib is an oral anticancer medicine that does not replace emergency care.

Mechanism of action: how larotrectinib works

Larotrectinib is a selective inhibitor of tropomyosin receptor kinases (TRK) TRKA, TRKB, and TRKC, which are activated by NTRK gene fusions. (1)

What larotrectinib is used for

Solid tumors with NTRK gene fusion

Larotrectinib is indicated for the treatment of adult and pediatric patients with solid tumors that have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, that are metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or have progressed following treatment. Patients are selected for therapy based on an FDA-approved test. (1)

Before taking larotrectinib

Do not take / not appropriate for

No contraindications are listed in the current US prescribing information. Patients are selected for larotrectinib based on an FDA-approved test for NTRK gene fusion. (all uses) (1)

Tell your clinician about

Any history of liver disease, abnormal liver tests, or current liver problems.
Symptoms such as dizziness, confusion, mood changes, memory problems, or trouble sleeping.
Bone pain, changes in mobility, or any deformity suggestive of a fracture.
Pregnancy or plans for pregnancy; the need for effective contraception during and shortly after treatment.
If you are breastfeeding or intend to breastfeed.
All other medicines you are taking, especially strong CYP3A4 inhibitors (e.g., itraconazole), strong CYP3A4 inducers (e.g., rifampin), or sensitive CYP3A4 substrates.

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How to take larotrectinib

Larotrectinib is taken by mouth twice daily. Adults and pediatric patients with a body surface area (BSA) of at least 1.0 m² take 100 mg twice daily. Pediatric patients with BSA less than 1.0 m² take 100 mg/m² twice daily.
The exact dose, formulation (capsule or oral solution), and duration are determined by the prescriber. Treatment continues until disease progression or unacceptable toxicity.
Any decision about changing the dose or continuing treatment should be made by your prescriber (see the missed-dose section below for what to do if you miss a scheduled dose).
If you experience dizziness, cognitive impairment, mood changes, or sleep disturbances, avoid driving or operating hazardous machinery.

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Procedures and treatment changes

Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1)

Missed dose

Contact your prescriber or treatment team about a missed dose. The reviewed label states that a missed dose should not be made up if the next scheduled dose is due within 6 hours.

Overdose

If you think you have taken too much larotrectinib, contact your healthcare provider or emergency services immediately. (1)

Side effects

Adverse reactions vary. Common effects include increased liver enzymes, anemia, hypoalbuminemia, musculoskeletal pain, fatigue, vomiting, diarrhea, and dizziness. Some effects require prompt medical attention.

Liver enzyme elevations (AST, ALT, alkaline phosphatase)

What to notice: Often asymptomatic; detected by blood tests. May be associated with liver injury.

What to do: Your healthcare provider will monitor liver function regularly (every 2 weeks for the first 2 months, then monthly) and may adjust treatment if necessary. (1)

Dizziness and central nervous system effects (cognitive impairment, mood disorders, sleep disturbances)

What to notice: This adverse-reaction category covers dizziness, cognitive impairment, mood disorders, and sleep disturbances.

What to do: Avoid driving or operating hazardous machinery if you experience these symptoms. Tell your treatment team if symptoms are severe, persistent, or interfere with daily activities. (1)

Fatigue or tiredness

What to notice: Unusual weakness or lack of energy that may affect your usual routine.

What to do: Discuss with your clinician if fatigue is significant or long-lasting. (1)

Gastrointestinal effects (nausea, vomiting, diarrhea, constipation, abdominal pain)

What to notice: These symptoms may occur; vomiting is more common in children.

What to do: Contact your clinician for assessment if these are severe or lead to dehydration; they will advise whether treatment should continue or be changed. (1)

Musculoskeletal pain (bone, muscle, or joint pain)

What to notice: General aches; new or worsening bone pain, difficulty moving, or a noticeable deformity may signal a fracture.

What to do: Report any new or worsening bone pain, changes in mobility, or a deformity to your oncologist promptly for evaluation. (1)

Skeletal fractures

What to notice: Bone pain, changes in mobility, or a deformity suggestive of a fracture.

What to do: Promptly report these symptoms to your oncologist for evaluation. (1)

Severe central nervous system effects

What to notice: Dizziness, cognitive impairment, mood disorders, or sleep disturbances that significantly affect your daily activities or safety.

What to do: Contact your clinician; the dose may be held, reduced, or you may be advised not to drive. (1)

Hepatotoxicity (liver injury)

What to notice: Not established from the sources reviewed: a specific patient-facing symptom list was not established in the sources reviewed for this page beyond liver-enzyme elevations found on blood tests.

What to do: Notify your healthcare provider for assessment; dose may be held, reduced, or permanently discontinued based on severity. (1)

Serious warnings

Hepatotoxicity — warning

Symptoms: Not established from the sources reviewed: a specific patient-facing symptom list was not established in the sources reviewed for this page beyond liver-enzyme elevations found on blood tests. Liver function is monitored regularly.

Action: Seek medical attention for evaluation; the dose may be held or adjusted. Do not change treatment on your own. (1)

Central nervous system effects — warning

Symptoms: Dizziness, cognitive impairment, mood disorders, sleep disturbances. These can affect your ability to drive or operate machinery safely.

Action: Avoid hazardous activities if affected. Contact your clinician for severe or persistent symptoms; a dose modification may be needed. (1)

Skeletal fractures — warning

Symptoms: Bone pain, changes in mobility, or a noticeable deformity.

Action: Notify your oncologist promptly for evaluation; imaging may be needed. (1)

Embryo-fetal toxicity — warning

Symptoms: Larotrectinib can cause fetal harm based on animal studies. It is not known to cause symptoms in the patient, but pregnancy must be avoided.

Action: Use effective contraception during treatment and for 1 week after the last dose. If you become pregnant, contact your doctor immediately. (1)

Interactions

Medicine or test	Effect	Action
Strong CYP3A4 inhibitors (e.g., itraconazole)	Significantly increases larotrectinib exposure (itraconazole increased the area under the curve 4.3-fold).	Tell your prescriber or pharmacist about this and all other medicines you take; the treating clinician will decide whether coadministration should be avoided or the larotrectinib dose adjusted. (1)
Moderate CYP3A4 inhibitors	May increase larotrectinib exposure.	Monitor for adverse reactions; the prescriber may adjust the dose if needed. (1)
Strong CYP3A4 inducers (e.g., rifampin)	Markedly decreases larotrectinib exposure (rifampin reduced the area under the curve by 81%).	Tell your prescriber or pharmacist about this and all other medicines you take; the treating clinician will decide whether coadministration should be avoided or the larotrectinib dose adjusted. (1)
Moderate CYP3A4 inducers	Decreases larotrectinib exposure.	The prescriber may decide to increase the dose (two-fold) if needed. (1)
Sensitive CYP3A4 substrates	Larotrectinib may increase their plasma concentrations.	Tell your prescriber or pharmacist about this and all other medicines you take; the treating clinician will decide whether coadministration should be avoided. (1)

Pregnancy, breastfeeding, kidney/liver function, age

Children and adolescents

Safety has been established in 154 pediatric patients. Vomiting, pyrexia, and infections are more common in children than in adults. Dosing is based on body surface area (BSA). The prescriber selects the appropriate formulation (capsule or oral solution) and monitors for adverse effects. (1)

Pregnancy and breastfeeding

Larotrectinib can cause fetal harm based on animal studies. Effective contraception must be used during treatment and for 1 week after the last dose. Breastfeeding is not advised during treatment and for 1 week after the last dose. Discuss the risks with your prescriber. (1)

Hepatic impairment

In patients with moderate-to-severe hepatic impairment (Child-Pugh B or C), the starting dose should be reduced by 50%. Dose adjustments and monitoring are managed by the prescriber. (1)

Renal impairment

No dose adjustment is needed in patients with renal impairment. (1)

Monitoring

Before starting

Confirm the presence of an NTRK gene fusion using an FDA-approved test and verify the clinical indication.
Obtain baseline liver function tests (ALT, AST, alkaline phosphatase, bilirubin).
Perform pregnancy testing in females of reproductive potential.
Evaluate for any pre-existing CNS symptoms, bone pain, or risk of fractures.
Review all concomitant medications for potential CYP3A4 interactions.

During treatment

Monitor liver function tests every 2 weeks for the first 2 months, then monthly thereafter. Dose adjustments (hold, reduce, or discontinue) are based on severity of liver enzyme elevations.
Assess clinically for CNS effects (dizziness, cognitive impairment, mood changes, sleep disturbances) and advise patients to avoid driving or hazardous machinery if affected.
Ask about any new or worsening bone pain, changes in mobility, or deformities; evaluate for fracture if symptoms suggest.
Re-evaluate the need for effective contraception and advise against breastfeeding.
Monitor for signs of infection, fatigue, and other adverse reactions.

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Storage

Capsules: Store at room temperature, 20°C to 25°C (68°F to 77°F). Oral solution: Refrigerate at 2°C to 8°C (36°F to 46°F); do not freeze. Discard the oral solution 90 days after opening a 100 mL bottle, or 31 days after opening a 50 mL bottle. Keep all medicine out of reach of children and follow any additional product-specific instructions.

Professional information

Clinician-facing context only. Use the current local product label, indication-specific dosing, and background oncology guidelines.

United States (US label)

Indication: Solid tumors with NTRK gene fusion

Dose summary: Adults and pediatric patients with BSA ≥1.0 m²: 100 mg orally twice daily. Pediatric patients with BSA <1.0 m²: 100 mg/m² orally twice daily. Continue until disease progression or unacceptable toxicity. Reduce starting dose by 50% in moderate-to-severe hepatic impairment (Child-Pugh B or C). No renal adjustment. For strong CYP3A4 interactions, see interactions section.

Renal context: No dose adjustment required in renal impairment. (1)

Mechanism of action

Hepatic guidance

In moderate-to-severe hepatic impairment, reduce starting dose by 50%. Use local product information and specialist judgement; this page does not provide impairment-specific dosing beyond what is indicated.

Overdose note

In case of suspected overdose, contact a healthcare provider or emergency services promptly. (1)

Frequently asked questions

What is larotrectinib used for?

It is used to treat solid tumors that have an NTRK gene fusion, when the cancer is advanced or surgery would cause serious problems, and other treatments are not suitable. (1)

Can I drive while taking larotrectinib?

Larotrectinib can cause dizziness, confusion, mood changes, and sleep disturbances. You should not drive or operate hazardous machinery if you experience these symptoms. Speak with your oncologist. (1)

Can I take larotrectinib with other medicines?

Some medicines can strongly affect larotrectinib levels. Tell your doctor about all your medicines, especially strong CYP3A4 inhibitors (like itraconazole) or inducers (like rifampin). Your prescriber may need to adjust doses or avoid certain combinations. (1)

What is the mechanism of action of larotrectinib?