Vitrakvi®Larotrectinib Sulfate Hard capsules

1. Indications and Usage
NTRK Fusion-Positive Solid Tumors: Treatment of adult and pediatric patients with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without known acquired resistance mutations, who have metastatic disease or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or have progressed on prior treatment .
Tumor Agnostic: Indications cover various tumor types (e.g., thyroid cancer, sarcoma, salivary gland cancer) provided the NTRK fusion status is confirmed .
2. Dosage and Administration
Administration: Oral administration. Hard capsules must be swallowed whole with water. Do not open, chew, or crush the capsules as contents are bitter .
Food Requirement: Can be taken with or without food. Avoid grapefruit or grapefruit juice .
Standard Dose:
Adults: 100 mg twice daily .
Pediatrics (BSA ≥1.0 m²): 100 mg twice daily .
Pediatrics (BSA <1.0 m²): 100 mg/m² twice daily (maximum single dose 100 mg) .
Missed Dose: If a dose is missed and it is less than 6 hours before the next scheduled dose, skip the missed dose. Do not take a double dose .
Dose Adjustment: Mandatory dose reduction (e.g., by 50%) for severe hepatotoxicity or neurotoxicity (Grade 3 or higher) .
3. Mechanism of Action
Larotrectinib is a potent, selective inhibitor of the tropomyosin receptor kinase (TRK) family (TRKA, TRKB, and TRKC).
It is encoded by the NTRK1, NTRK2, and NTRK3 genes.
By blocking these kinases, larotrectinib inhibits the phosphorylation of TRK, leading to inhibition of tumor cell proliferation and induction of apoptosis .
4. Safety and Warnings
Hepatotoxicity: Elevations in ALT and AST are common. Monitor liver function tests before initiation and during treatment .
Neurotoxicity: Can cause CNS effects (e.g., dizziness, cognitive impairment, ataxia). Patients should avoid driving if these occur .
Embryo-Fetal Toxicity: May cause fetal harm. Contraception is required for females and males during treatment and for at least 1 week after the final dose .
Muscle Damage: Monitor Creatine Kinase (CK) levels if muscle pain or weakness occurs .
5. Adverse Reactions
Common adverse reactions (incidence ≥20%) include:
General: Fatigue, pyrexia.
Gastrointestinal: Nausea, diarrhea, vomiting, constipation, dysgeusia.
CNS: Dizziness, cognitive impairment.
Laboratory Abnormalities: Increased AST, increased ALT, anemia .
6. Drug Interactions
CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors (e.g., ketoconazole) as they increase Larotrectinib exposure. If unavoidable, reduce dose by 50% .
CYP3A Inducers: Avoid co-administration with strong CYP3A inducers (e.g., rifampin) as they reduce efficacy .
7. Pharmaceutical Information
Chemical Name: Larotrectinib Sulfate .
Molecular Formula: C21H23ClN6O4 · H2SO4 .
Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .