larotrectinib

Larotrectinib is a highly selective tyrosine kinase inhibitor that targets and inhibits the activity of TRKA, TRKB and TRKC proteins produced by neurotrophic tyrosine receptor kinase (NTRK) gene fusion, blocking their downstream signaling pathways, thereby inhibiting the proliferation and survival of tumor cells.

1. Drug name

1. Generic name: Larotrectinib

2. Trade name: VITRAKVI®

2. Indications

For the treatment of adults and children with solid tumors , the following conditions must be met:

The presence of neurotrophic tyrosine receptor kinase (NTRK) gene fusion has been confirmed by testing, and there are no known acquired drug resistance mutations;

The tumor is metastatic or surgical resection may cause serious complications;

There is no satisfactory alternative treatment or disease progression after previous treatment.

3. Specifications and properties

1. Specifications: Capsules: 25mg, 100mg (based on larotrectinib);

2. Properties: Capsules: white opaque hard capsules, printed with blue "LOXO" and dose identification (25mg or 100mg);

IV. Main ingredients

1. Active ingredient: Larotinib (calculated as larotinib sulfate, 25mg capsule contains 30.7mg sulfate, 100mg capsule contains 123mg sulfate, oral solution contains 24.6mg/mL sulfate).

2. Excipients: Capsule: gelatin, titanium dioxide, edible ink;

5. Usage and dosage

1. Adults and children with body surface area ≥1.0m²: 100mg orally, twice a day;

2. Children with body surface area <1.0m²: 1 00mg/m² orally, twice daily (maximum dose not exceeding 100mg/time);

3. Medication method: Swallow the capsule whole, do not chew or crush; oral solution needs to be measured with a special oral syringe;

4. Course of treatment:Continue treatment until disease progression or intolerable toxicity occurs.

6. Dose adjustment

1. Gradually reduce the dose according to the severity of adverse reactions:

First dose reduction: 75mg (or 75mg/m²) twice a day;

Chapter Second reduction: 50 mg (or 50 mg/m²) twice a day;

Third reduction: 100 mg once a day (or 25 mg/m² twice a day);

Permanent discontinuation if the dose after the third reduction cannot be tolerated.

2. Specific adjustments are made to target serious adverse reactions such as neurotoxicity and hepatotoxicity.

7. Medication Precautions

1. Before and after meals: It can be taken with food or on an empty stomach. Food has little effect on absorption;

2. Missed dose: If a dose is missed, it should be taken within 6 hours before the next dose, otherwise the dose will be skipped;

3. Vomiting: There is no need to retake the dose if there is vomiting after taking the medicine. Take the next dose as planned.

4. Others:

Avoid driving or operating dangerous machinery during treatment because neurotoxic symptoms such as dizziness may occur;

Avoid eating grapefruit or drinking grapefruit juice, and avoid using St. John's wort.

8. Medication for Special Populations

1. Liver insufficiency:

Mild (Child-PughA) does not require dose adjustment;

Moderate to severe (Child-PughB or C) the starting dose needs to be reduced by 50%.

2. Renal insufficiency: No dose adjustment is required for any severity.

3. Elderly people: The data is limited and should be used with caution.

4. Pregnant women and lactation period:

Pregnant women may cause fetal harm, and patients of childbearing age need to take effective contraceptive measures until 1 week after the last dose;

Lactation is contraindicated, and breastfeeding is not recommended within 1 week after stopping the drug.

9. Adverse reactions

1. Common adverse reactions** (≥20%): Fatigue (37%), nausea (29%), dizziness (28%), vomiting (26%), increased AST (45%), cough (26%), increased ALT (45%), constipation (23%), diarrhea (22%).

2. Serious adverse reactions:

Neurological toxicity (53%, including delirium, dysarthria, ataxia, etc.);

Hepatotoxicity (ALT/AST elevation, 45%);

Others: anemia (42%), neutropenia (23%).

3. Laboratory abnormalities: Hypoalbuminemia (35%), elevated alkaline phosphatase (30%).

10. Contraindications

None.

11. Drug interactions

1. Strong CYP3A4 inhibitors (such as itraconazole): Avoid combined use. If combined use is necessary, the dose of larotrectinib should be reduced by 50%;

2. Strong CYP3A4 inhibitors 3A4 inducers (such as rifampin): Avoid combined use. If combined use is necessary, the dose of larotrectinib should be increased to 2 times;

3. Sensitive CYP3A4 substrates (such as midazolam): Avoid combined use because larotinib may increase its plasma concentration.

12. Storage method

Capsules: Store at room temperature (20°C–25°C), allow short periods of 15°C–30°C.