Larotrectinib
TRK and RET inhibitors (tumour-agnostic kinase inhibitors)
TRK and RET inhibitors (tumour-agnostic kinase inhibitors)High alert
An error with this medicine can cause serious harm: double checks and protocols are used.
Oral TRK inhibitor for solid tumours with an NTRK gene fusion, in adults and children, whatever the organ. Watch for dizziness, confusion and liver effects.
Quick facts
- Group
- TRK and RET inhibitors (tumour-agnostic kinase inhibitors)
- Target
- TRKA, TRKB and TRKC receptor tyrosine kinases (genes NTRK1, NTRK2, NTRK3)
- Used for
- Solid tumours
- Key effects
- Fatigue · Nausea · Cough
- Monitor
- Liver tests regularly · Neurological symptoms
- ATC
- L01EX12
No doses: the clinician sets them by the current guideline.
Mechanism of action
NTRK gene fusions create TRK fusion proteins whose kinase is always switched on and drives tumour growth. Larotrectinib inhibits the TRKA, TRKB and TRKC kinases, blocking the constant signal from these fusion proteins. It is not active against TRK kinases that have acquired resistance mutations, which is how tumours can escape.
- An NTRK fusion makes an always-on TRK kinase
- Larotrectinib blocks the TRK kinase site
- Growth signals from the fusion protein stop
- Resistance mutations in TRK can restore growth
Indications
- Solid tumours with an NTRK gene fusion and no known acquired resistance mutation, in adults and children (including infants), that are metastatic or unresectable and have no satisfactory alternative treatment (tumour-agnostic indication).
Adverse effects
Common
- Fatigue, dizziness
- Nausea, vomiting, constipation, diarrhoea
- Cough, nasal congestion
- Muscle weakness, weight gain
- Raised liver enzymes, low blood counts
Contraindications
- No absolute contraindications in the label; caution in liver impairment
Key interactions
- Grapefruit and grapefruit juice
- Avoided: can raise larotrectinib levels.
- St John's wort
- Can lower larotrectinib levels; avoided.
What is monitored
- Test showing an NTRK fusion before starting
- Liver tests regularly
- Neurological symptoms
- Bone pain or fractures
Administration and safety
- Oral capsules swallowed whole, or the oral solution measured with the oral syringe supplied, never a kitchen spoon.
- The oral solution is kept in the refrigerator.
- Hazardous oral chemotherapy: handled with gloves and kept away from children; caregivers who are pregnant avoid handling it.
Pregnancy and breastfeeding
May harm the fetus; a pregnancy test is done and effective contraception is used during and shortly after treatment; breastfeeding is avoided.
Nursing care
- Ask about dizziness, unsteadiness, confusion or memory problems; assess fall risk.
- Review liver tests before refills.
- Ask about bone pain.
- Teaching: do not drive or use machines until the effect on alertness is known; avoid grapefruit and St John's wort; use effective contraception.
Pharmacokinetics
- Absorption
- Oral capsule or oral solution, with or without food.
Test yourself
Think of the answer, then tap the question to see it.
Which kinases does larotrectinib inhibit?
TRKA, TRKB and TRKC.
What genetic finding is needed before larotrectinib is used?
An NTRK gene fusion in the tumour.
Why does larotrectinib cause dizziness and confusion?
TRK receptors are neurotrophin receptors active in the nervous system.
Connections
← Back to the class: TRK and RET inhibitors (tumour-agnostic kinase inhibitors)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Larotrectinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Larotrectinib Sulfate - NCI (National Cancer Institute, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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