List of Chinese instructions for Dabrafenib/Dabrafenib

1. Generic name: Dabrafenib, Dabrafenib

Product name: TAFINLAR, TAFINLAR

Other names: dabrafenib, dabrafenib mesylate capsules

2. Indications:

Dabrafenib is indicated to treat the following conditions:

1. Melanoma:

(1) BRAF V600E mutation-positive unresectable or metastatic melanoma: As tested in FDA-approved trials, dabrafenib can be used as a single drug to treat patients with BRAF V600E mutation-positive unresectable or metastatic melanoma.

(2) Unresectable or metastatic melanoma positive for BRAF V600E or V600K mutations: Dabrafenib is used in combination with trametinib to treat patients with unresectable or metastatic melanoma who have BRAF V600E or V600K mutations detected by FDA-approved tests.

(3) Adjuvant treatment of BRAF V600E or V600K mutation-positive melanoma: Dabrafenib is used in combination with trametinib for the adjuvant treatment of melanoma patients with BRAF V600E or V600K mutations detected in FDA-approved trials, and patients with lymph node involvement after complete resection.

2. BRAF V600E mutation-positive metastatic non-small cell lung cancer (NSCLC): Dabrafenib in combination with trametinib is used to treat patients with metastatic NSCLC with BRAF V600E mutations detected in FDA-approved trials.

3. BRAF V600E mutation-positive locally advanced or metastatic anaplastic thyroid cancer (ATC): Dabrafenib is used in combination with trametinib to treat patients with BRAF V600E mutation-positive locally advanced or metastatic ATC and no satisfactory local-regional treatment options.

4. BRAF V600E mutation-positive unresectable or metastatic solid tumors: Dabrafenib is indicated in combination with trametinib for the treatment of adult and pediatric patients 1 year of age and older with BRAF V600E mutation-positive unresectable or metastatic solid tumors who have progressed after prior treatment and for whom there are no satisfactory alternative treatments.

5. BRAF V600E mutation-positive low-grade glioma (LGG): Dabrafenib combined with trametinib is used to treat pediatric patients 1 year old and above with BRAF V600E mutation-positive LGG who require systemic treatment.

3. Usage and dosage:

1. Before treatment: Before starting treatment with dabrafenib as a single drug, it is necessary to confirm the presence of BRAF V600E mutation in the tumor sample; before starting combined treatment with dabrafenib and trametinib, it is necessary to confirm the presence of BRAF V600E or V600K mutation in the tumor sample.

2. Recommended dosage: Dabrafenib is available in the form of capsules and should be taken at least 1 hour before meals or 2 hours after meals, or at the same time every day, with an interval of about 12 hours. Swallow capsules whole; do not open, break or squeeze them. The recommended dose of dabrafenib for adult patients is 150 mg orally twice daily; for pediatric patients weighing at least 26 kg, the recommended dose is based on body weight; for patients weighing 26-37 kg, the dose is 75 mg orally twice daily; for patients 38-50 kg, the dose is 100 mg orally twice daily; for patients weighing less than 26 kg, the recommended dose has not been determined.

3. Dose adjustment: If a patient experiences intolerable adverse reactions after treatment with dabrafenib, the doctor may adjust the dose of the drug based on the severity of the condition, such as reducing, interrupting or stopping treatment. For adult patients treated with dabrafenib, if the recommended dose is 150 mg orally twice a day, the first dose can be reduced to 100 mg orally twice a day; the second dose can be reduced to 75 mg orally twice a day; the third dose can be reduced to 50 mg orally twice a day; if dabrafenib capsules 50 mg orally twice a day are not tolerated, please permanently discontinue treatment.

4. Adverse reactions:

In clinical studies of dabrafenib as a single agent, the most common side effects include papilloma (warts), headache, nausea, vomiting, hyperkeratosis (thickening and hardening of the skin), alopecia, rash, joint pain, fever, and fatigue; when combined with trametinib, the most common side effects Common side effects include fever, fatigue, nausea, chills, headache, diarrhea, vomiting, arthralgia, and rash; the most common grade 3 or 4 laboratory abnormalities are decreased neutrophil count, increased alanine aminotransferase, and increased aspartate aminotransferase.

5. Supply and storage:

Dabrafenib50 mg and 75 mg capsules are available and can be stored at 20°C to 25°C (68°F to 77°F); tolerances are allowed between 15°C and 30°C (59°F and 86°F). Store desiccant and aliquot in original bottles.

6. Special groups:

Due to known inherent resistance to BRAF inhibition, dabrafenib is not suitable for the treatment of patients with colorectal cancer; nor is it suitable for the treatment of patients with wild-type BRAF solid tumors.

7. Mechanism of action:

Dabrafenib is an inhibitor of some mutant forms of BRAF kinase, with in vitro IC50 values of 0.65, 0.5 and 1.84nM for BRAF V600E, BRAF V600K and BRAF V600D enzymes, respectively. Dabrafenibalso inhibits wild-typeBRAF and CRAF kinases with IC50 values u200bu200bof 3.2 and 5.0nM, respectively, as well as other kinases such as SIK1, NEK11 and LIMK1 at high concentrations. Some mutations in the BRAF gene, including those leading to BRAF V600E, can lead to constitutively activated BRAF kinase, thereby stimulating tumor cell growth.

Dabrafenib inhibits cell growth in various BRAF V600 mutation-positive tumors in vitro and in vivo. Dabrafeniband trametinib target two different kinases in the RAS/RAF/MEK/ERK pathway. The combination of dabrafenib and trametinib resulted in greater growth inhibition of BRAF V600 mutation-positive tumor cell lines in vitro and prolonged inhibition of tumor growth in BRAF V600 mutation-positive tumor xenografts compared with either agent alone.

8. Overdose:

There is no information regarding dabrafenib overdose. Because dabrafenib is highly bound to plasma proteins, hemodialysis may be ineffective in treating dabrafenib overdose.