Formulation and specifications: Capsules: 50mg, 75mg
Indications:
1. Darafenib in combination with trametinib is indicated for the treatment of patients with unresectable or metastatic melanoma positive for the BRAF V600 mutation.
2. Dabrafenib in combination with trametinib is indicated for the adjuvant treatment of patients with BRAF V600 mutation-positive stage III melanoma after complete resection.
Key points for rational drug use:
1. This product in combination with trametinib must be tested for BRAF V600 mutation by a test approved by the State Drug Administration before treatment, and patients who are confirmed to be BRAF V600 mutation-positive should receive this product only. This product in combination with trametinib is not indicated for patients with BRAF wild-type melanoma.
2. The recommended dose of darafenib is 150 mg twice daily (300 mg total daily dose). This product should be used in combination with trametinib until disease progression or intolerable toxic effects occur.
3. Darafenib should be taken at least 1 hour before or at least 2 hours after a meal, with an interval of approximately 12 hours between doses. It should be taken at the same time each day. If a dose of darafenib is missed and less than 6 hours before the next dose, it should not be made up. When dabrafenib is used in combination with trametinib, trametinib should be taken once daily at the same time each day as dabrafenib given in the morning or evening. Do not open, crush or break dalafenib capsules.
4. Common adverse reactions when dabrafenib is given in combination with trametinib therapy include: fever, chills, rash, headache, dizziness, arthralgia, and cough. If treatment-related toxicity occurs, both treatments should be concurrently dose reduced, interrupted or discontinued. If adverse reactions associated with dabrafenib occur (uveitis, non-cutaneous malignancies), only dose adjustment of dabrafenib therapy is required.
5. Patients with mild hepatic impairment and patients with mild to moderate renal impairment do not require dose adjustment at first treatment. Dabrafenib should be used with caution in patients with moderate to severe hepatic impairment, and in patients with severe renal impairment. No initial dose adjustment is required in elderly patients (≥65 years). The safety and efficacy of darafenib in children and adolescents (<18 years of age) have not been established.
6. Drugs that are potent inhibitors or inducers of CYP2C8 or CYP3A4 may affect the blood levels of dalafenib. Where possible, substitution of inhibitors or inducers of CYP2C8 and CYP3A4 in currently administered drugs should be considered when receiving dabrafenib.
*7. In the US and EU, dabrafenib in combination with trametinib is approved for the treatment of metastatic NSCLC with BRAF V600E and BRAF V600 mutations, respectively. In the United States, dabrafenib in combination with trametinib is approved for the treatment of locally advanced or metastatic undifferentiated thyroid cancer with BRAF V600E mutation. Both indications are currently unapproved in China and may be used with adequate communication with patients. In the United States, the recommended dose is dabrafenib 150 mg twice daily.