Dabrafenib is a small molecule kinase inhibitor that inhibits tumor cell proliferation by targeting BRAF serine/threonine kinase activity, blocking abnormal activation of the MAPK signaling pathway.

1、 Drug name

1. Common name: Dalafenib

2. Product Name: TAFINLAR ®

3. English name: Dabrafenib

2、 Indications

This product is a kinase inhibitor, suitable for:

1. Single drug therapy for unresectable or metastatic melanoma confirmed by FDA approved testing as BRAFV600E mutation positive.

Used in combination with Trametinib for the following situations:

2. Unresectable or metastatic melanoma confirmed by FDA approved testing as BRAFV600E or V600K mutation positive.

3. Adjuvant therapy for BRAFV600E or V600K mutation positive melanoma with complete resection and lymph node involvement, confirmed by FDA approved testing.

4. Confirmed by FDA approved testing as BRAFV600E mutation positive metastatic non-small cell lung cancer (NSCLC).

5. Locally advanced or metastatic thyroid undifferentiated carcinoma (ATC) confirmed by FDA approved testing as BRAFV600E mutation positive and without satisfactory local treatment options.

6. Adult and pediatric patients aged 6 years and above with BRAFV600E mutation positive, unresectable or metastatic solid tumors, who have experienced disease progression after previous treatment and have no satisfactory alternative treatment options (this indication is for accelerated approval).

7. Pediatric patients aged 1 year and above with BRAFV600E mutation positive and requiring systemic treatment for low-grade glioma (LGG).

8. Usage restrictions: Not applicable for the treatment of colorectal cancer patients (due to known inherent resistance to BRAF inhibition); Not suitable for the treatment of BRAF wild-type solid tumor patients.

3、 Specifications and characteristics

Capsules: 75 milligrams.

4、 Main components

1. Active ingredient: dalafenib mesylate.

2. Capsule excipients: colloidal silica, magnesium stearate, microcrystalline cellulose. The capsule shell contains hydroxypropyl methylcellulose, iron oxide red, and titanium dioxide.

5、 Usage and dosage

1. Recommended dosage for adult patients: 150mg (2 75mg capsules), twice daily, orally.

2. Recommended dosage for pediatric patients: use capsules based on body weight.

3. Medication timing: Take at approximately the same time every day, with an interval of about 12 hours. It should be taken at least 1 hour before meals or at least 2 hours after meals.

4. Duration of treatment:

Unresectable or metastatic melanoma, solid tumor, metastatic NSCLC, locally advanced or metastatic ATC: until disease progression or unacceptable toxicity occurs.

Adjuvant treatment for melanoma: Until disease recurrence or unacceptable toxicity occurs, up to 1 year.

Pediatric LGG patients: until disease progression or unacceptable toxicity occurs.

6、 Dose adjustment

1. For adverse reactions such as newly diagnosed malignant tumors, cardiomyopathy, uveitis, fever, skin toxicity, bleeding, etc., dosage should be temporarily suspended, reduced, or permanently discontinued according to the severity.

2. The dose reduction plan has specific regulations based on the initial dose and body weight. If the lowest dose cannot be tolerated, the medication will be permanently discontinued.

7、 Medication precautions

1. Medication time: It should be taken on an empty stomach, 1 hour before or 2 hours after meals.

2. Missed dose: If a dose is missed, it should be taken immediately when remembered. But if the next scheduled medication time is less than 6 hours away, skip this dose and take the next dose according to the original plan. Do not take two doses at the same time to make up for missed doses.

3. Vomiting after taking medication: If vomiting occurs after taking medication, there is no need to take additional doses, and the next dose should be taken according to the original plan.

4. Capsules: should be swallowed whole and should not be opened, crushed, or chewed.

8、 Medication for special populations

1. Pregnant women: Based on animal data and mechanisms of action, there may be fetal harm, and pregnant women should be informed of the risks.

2. Women/Men of childbearing age: Women of childbearing age should take effective non hormonal contraceptive measures during treatment and 2 weeks after the last dose (as this product may render hormonal contraceptives ineffective). Male patients (including those who have undergone sterilization) should use condoms when having sexual intercourse with a female partner who is capable of reproduction during this period.

3. Breastfeeding period: It is recommended not to breastfeed during the treatment period and within 2 weeks after the last dose.

4. Pediatric medication: It has been established to be used in combination with trametinib for specific pediatric indications. The safety and efficacy of monotherapy in pediatric patients have not yet been established.

5. Medication for the elderly: No overall efficacy difference was observed between elderly and young adult patients, but the incidence of certain adverse reactions (such as peripheral edema and anorexia) may increase in the elderly.

6. Liver injury patients: Mild liver injury does not require dose adjustment. The appropriate dosage for patients with moderate to severe liver injury has not yet been established.

9、 Adverse reactions

Common adverse reactions (≥ 20%) vary depending on the monotherapy or combination with trametinib, as well as different indications, mainly including:

2. Single drug: hyperkeratosis of the skin, headache, fever, joint pain, papilloma, hair loss, palmar and plantar redness and swelling syndrome, etc.

3. Combined use with trametinib (depending on different cancers): fever, rash, chills, headache, joint pain, cough, fatigue, nausea, vomiting, diarrhea, decreased appetite, edema, bleeding, difficulty breathing, muscle pain, dry skin, abdominal pain, acne like dermatitis, etc.

Serious adverse reactions: including newly diagnosed primary malignant tumors (skin and non skin), bleeding, cardiomyopathy, uveitis, severe fever, severe skin toxicity, hyperglycemia, hemolytic anemia in G6PD deficient patients, etc.

10、 Contraindications

None.

11、 Drug interactions

1. Simultaneous use with potent CYP3A4 or CYP2C8 inhibitors should be avoided. If unavoidable, close monitoring of adverse reactions is necessary.

2. This product may reduce the efficacy of drugs metabolized by CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2B6 (such as certain hormonal contraceptives and warfarin). When used in combination, alternative drugs or monitoring of efficacy loss should be considered.

12、 Storage method

Store at room temperature of 20 ° C to 25 ° C (68 ° F to 77 ° F) and allow for short distance transportation between 15 ° C to 30 ° C (59 ° F to 86 ° F).

Dabrafenibinformation