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Information about Larotrectinib

Introduction Larotrectinib is a selective inhibitor of neurotrophin receptor kinase (NTRK) that is used in the therapy of solid tumors harboring NTRK gene fusions.

Liver safety of Larotrectinib

Larotrectinib is associated with a high rate of serum aminotransferase elevations during therapy but has not been linked to instances of clinically apparent liver injury with jaundice.

Mechanism of action of Larotrectinib

Larotrectinib (lar" oh trek' ti nib) is an orally available, small molecule inhibitor of the tropomyosin receptor kinases (TRK-A, -B and -C). The genes of TRK are found to be oncogenic drivers in many solid tumors including gliomas and sarcomas. The tumors harbor a fusion product of the proto-oncogene family and overexpress the neurotrophin receptor kinases which results in abnormal cell growth. Larotrectinib has activity against all three forms of TRK and has been shown to be effective in prolonging progression free survival in children and adults with various solid tumors harboring an NTRK gene fusion.

FDA approval information for Larotrectinib

Larotrectinib received accelerated approval for use in the United States in 2018 for the treatment of advanced or metastatic solid tumors that have NTRK gene fusion.

Dosage and administration for Larotrectinib

Larotrectinib is available in capsules of 25 and 100 mg and as an oral solution of 20 mg/mL under the brand name Vitrakvi. The recommended dose in adults is 100 mg orally twice daily, the dose in children and small adults being adjusted to body surface area.

Side effects of Larotrectinib

Side effects are common and include fatigue, nausea, vomiting, constipation, diarrhea, dizziness and cough. Uncommon, but potentially serious side effects include neurotoxicity (delirium, dysarthria, dizziness, gait disturbance, tremor), hepatotoxicity (ALT and AST elevations) and embryo-fetal toxicity.

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