Lotenib/Vitrakvi/Laronib Drug LOXO-101,ARRY-470

Product Name: Larotrectinib

English Name: Larotrectinib

Specification: 100 mg × 30 Capsules/Box

Manufacturer: Everest Pharmaceuticals

This product is indicated for the treatment of the following patients: adult and pediatric patients with solid tumors that harbor an *NTRK* gene fusion (*NTRK1*, *NTRK2*, or *NTRK3* gene fusion).

Larotrectinib is a broad-spectrum anticancer agent effective against a wide variety of tumors. It is effective in treating the following types: lung cancer, thyroid cancer, melanoma, gastrointestinal cancer, colon cancer, soft tissue sarcoma, salivary gland tumors, infantile fibrosarcoma, appendiceal cancer, breast cancer, cholangiocarcinoma, pancreatic cancer, and 17 other tumor types.

Dosage and Administration This product should be used under the guidance of an experienced physician. Prior to initiating treatment, the presence of an *NTRK* gene fusion should be confirmed using a validated diagnostic assay. The diagnosis of TRK fusion tumors can be established through specific testing methods, including Next-Generation Sequencing (NGS) and Fluorescence *in situ* Hybridization (FISH) to identify *NTRK* gene fusions. Patients whose tumors harbor an *NTRK* gene fusion are candidates for treatment with Larotrectinib.

Recommended Dosage

Adult Dosage: The usual dosage of Larotrectinib is 100 mg taken orally twice daily. Swallow Vitrakvi capsules whole; do not chew or crush the capsules. May be taken with or without food. If you vomit after taking a dose of Larotrectinib, take the next dose at the scheduled time. Continue treatment until disease progression or until unacceptable toxicity occurs.

Pediatric Dosage: For pediatric patients, the dosage is 100 mg/m² taken orally twice daily (with a maximum single dose of 100 mg). For pediatric patients with a Body Surface Area (BSA) of less than 1.0 m², the recommended dosage of Larotrectinib is 100 mg/m² taken orally twice daily. May be taken with or without food. It has not been established whether Larotrectinib is safe and effective in children younger than 1 month of age.

Dosage Adjustments for Adverse Reactions: In the event of Grade 3 or 4 adverse reactions, reduce the dosage until the reaction improves or resolves to Grade 1. If the adverse reaction resolves within 4 weeks, resume treatment at the next scheduled dose. If the adverse reaction does not resolve within 4 weeks, permanently discontinue Larotrectinib. Side Effects and Adverse Reactions: The most common side effects of larotrectinib include: fatigue, nausea, cough, constipation, diarrhea, dizziness, vomiting, and elevated blood levels of the liver enzymes AST and ALT. Most patients (93%) experienced Grade 1 or Grade 2 adverse events (AEs). No treatment-related Grade 4 AEs occurred; the most common treatment-related Grade 3 AEs included: increased ALT or AST levels (5%), anemia (2%), decreased neutrophil count (2%), nausea (2%), and dizziness (2%).

Common Concerns:

1. Nervous System Issues: If you experience any adverse reactions—such as difficulty speaking, dizziness, coordination problems, tingling, numbness, or a burning sensation in your hands or feet—please inform your healthcare provider. Your doctor may temporarily suspend treatment, reduce the dosage, or permanently discontinue larotrectinib.

2. Liver Issues: Your healthcare provider will conduct blood tests to monitor your liver function during treatment. If you develop signs of liver problems—including loss of appetite, nausea or vomiting, or pain in the upper right side of your stomach—treatment may be temporarily suspended, the dosage reduced, or the medication permanently discontinued.

3. Pregnancy or Planning for Pregnancy: Larotrectinib may harm an unborn baby; therefore, you should not become pregnant while undergoing treatment. Women of childbearing potential should use effective contraception (birth control) during treatment and for at least one week after taking the final dose. Discuss appropriate contraceptive methods with your doctor.

4. Breastfeeding: It is currently unknown whether larotrectinib passes into breast milk. Do not breastfeed during treatment or for one week after taking the final dose.

5. Medications: Inform your healthcare provider about all medications you are taking, including prescription and over-the-counter drugs, vitamins, and herbal supplements. Certain other medications may affect how Vitrakvi works.

Storage:

*   Store capsules at room temperature (20°C to 25°C).

*   Store the oral solution under refrigeration (2°C to 8°C); do not freeze. The solution is stable for 90 days; use within 90 days of first opening the bottle. Treatment Efficacy: According to data released by the FDA, 73% of patients demonstrated a duration of response of 6 months or longer; 63% demonstrated a duration of response of 9 months or longer; and 39% demonstrated a duration of response of 12 months or longer. The U.S. FDA states: "Precision cancer therapy with an efficacy rate as high as 75%!" In February 2018, the *New England Journal of Medicine (NEJM)*—one of the world's four leading authoritative medical journals—published the results of three clinical studies assessing the safety and efficacy of the anticancer drug Larotrectinib (also known as larotrectinib). These results indicated that, for patients aged 4 months to 76 years undergoing treatment for 17 different types of cancer, the overall response rate was 75%. These findings were subsequently confirmed by the FDA. Shortly thereafter, at the European Society for Medical Oncology (ESMO) conference held in October 2018 (ESMO 2018), clinical data regarding the use of Larotrectinib to treat adult and pediatric patients with TRK fusion cancers—encompassing 24 distinct tumor types—revealed the following: Overall Response Rate: 80%; Partial Response Rate: 62%; and Complete Response Rate: 18%.

Product Specifications

Product Name: Larotrectinib (larotrectinib) 100 mg × 30 Capsules/Box | Lotenib/Vitrakvi/Laronib | Drug LOXO-101, ARRY-470

Common Name: Larotrectinib

Active Ingredient: larotrectinib

Dosage Form: Capsule

Specification: 100 mg × 30 Capsules/Box

Manufacturer: ZhuFeng Pharmaceutical

Indications: Larotrectinib is a kinase inhibitor indicated for the treatment of adult and pediatric patients with solid tumors that:

Harbor a neurotrophic receptor tyrosine kinase (*NTRK*) gene fusion without a known acquired resistance mutation;

Are metastatic or where surgical resection is likely to result in severe morbidity; and

Have no satisfactory alternative treatments or have progressed following treatment.

Dosage and Administration: Select patients for Larotrectinib treatment based on the presence of an *NTRK* gene fusion.

Recommended dosage for adult and pediatric patients with a body surface area (BSA) of at least 1.0 m²: 100 mg orally, twice daily. Recommended dosage for pediatric patients with a body surface area of less than 1.0 m²: 100 mg/m², twice daily.