Formulation and specifications: Tablets: 0.5mg, 2mg
Indications:
1. Trametinib in combination with dabrafenib is indicated for the treatment of patients with unresectable or metastatic melanoma positive for BRAF V600 mutation.
2. Trametinib in combination with dabrafenib 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. Trametinib combined with dabrafenib treatment must be preceded by BRAF V600 mutation testing by an assay approved by the State Drug Administration, and patients who are confirmed to be BRAF V600 mutation positive can only receive this product. This product in combination with darafenib is not indicated for patients with BRAF wild-type melanoma.
2. The recommended dose of trametinib is 2 mg once daily orally and is required in combination with dabrafenib until disease progression or intolerable toxic effects occur. The first dose is reduced to 1.5 mg once daily; the second dose is reduced to 1 mg once daily; and if 1 mg once daily is not tolerated, the drug is permanently discontinued.
3. Trametinib should be taken at least 1 hour before a meal or at least 2 hours after a meal. Trametinib should be taken at the same time each day. If a dose of this product is missed, it must be made up no later than 12 hours prior to the next scheduled dose. If it is less than 12 hours before the next scheduled dose, it should not be made up. When this product is combined with dabrafenib, it should be taken once daily at the same time each day as dabrafenib administered in the morning or evening. The product should not be chewed or crushed.
4. When trametinib is given in combination with dabrafenib treatment, common adverse reactions include: fever, chills, rash, headache, dizziness, arthralgia, cough, etc. If treatment-related toxicity occurs, both treatments should be concurrently dose reduced, interrupted or discontinued. For adverse reactions primarily associated with trametinib (retinal vein occlusion, retinal pigment epithelial detachment, interstitial pneumonia, and simple venous thromboembolism), only dose adjustment of trametinib is required.
5. No dose adjustment is required in patients with mild hepatic impairment and mild to moderate renal impairment. Dabrafenib should be used with caution in patients with moderate to severe hepatic impairment and 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 metabolized by hydrolases may affect trametinib exposure and drug-drug interactions cannot be ruled out. Trametinib should be used with caution in combination with potent P-glycoprotein inhibitors.
*7. Trametinib in combination with darafenib is approved for the treatment of metastatic NSCLC with BRAF V600E and BRAF V600 mutations in the US and EU, respectively. In the United States, trametinib in combination with dabrafenib 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 trametinib 2 mg once daily.